Disease Outcome Research Articles

Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials

GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m2 or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1·73 m2), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0·82, 95% CI 0·73-0·93; I2 =26·41%), kidney failure by 16% (HR 0·84, 0·72-0·99; I2 =0%), MACE by 13% (HR 0·87, 0·81-0·93; I2 =49·75%), and all-cause death by 12% (HR 0·88, 0·83-0·93; I2 =0%). The effect on the composite kidney outcome (HR 0·81, 95% CI 0·72-0·92; I2 =23·11%), kidney failure (HR 0·84, 0·72-0·98; I2 =0%), MACE (HR 0·86, 0·80-0·92; I2 =48·9%), and all-cause death (HR 0·87, 0·82-0·91; I2 =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (pheterogeneity >0·05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0·95, 95% CI 0·90-1·01; I2 =88·5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1·51, 95% CI 1·18-1·94; I2 =96·3%). We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. None.

Fluorescent Chemosensors in the Creation of a Commercially Available Continuous Glucose Monitor.

Fully automated insulin delivery (i.e., an artificial pancreas) would revolutionize diabetes disease management, minimize negative secondary disease outcomes, and simultaneously reduce health care costs and system burdens. Continuous glucose monitoring (CGM) is an essential aspect of the artificial pancreas. Abiotic fluorescent chemosensors play a key role in generating long-lived CGM sensors for this purpose. In this Perspective, we detail our initial discoveries of chemosensors for saccharides, as well as the development and advancement of bis((o-aminomethylphenyl)boronic acid)anthracene-based sensors for commercial use. While a few companies have sought to bring a copolymerized diboronic acid CGM sensor to the market, Senseonics is the only one, to date, to have done so. In this case, the system has been approved in the U.S. and Europe to provide accurate CGM for up to 365 days with a single sensor and can be integrated directly with an insulin pump, bringing an artificial pancreas one step closer to realization.

The relationship between composite inflammatory indicators and short-term outcomes in patients with heart failure

BackgroundInflammatory markers are considered reliable indicators for predicting adverse outcomes of cardiovascular disease. However, the prognostic significance of composite inflammatory indicators such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and inflammatory prognosis index (IPI), in predicting mortality among heart failure (HF) patients remains unknown. MethodsWe analyzed data from 1981 patients with HF. The composite inflammatory indicators were calculated based on laboratory test. The endpoint of the study was mortality within six months of follow-up. Cox proportional hazards model and restricted cubic spline analysis were used to assess the association between inflammatory markers and outcomes. The incremental predictive value of composite inflammatory indicators was evaluated using C-index, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). ResultsSII, SIRI, and IPI were linearly associated with the risk of death. Compared to the first tertile, the hazard ratios and 95 % confidence intervals (CIs) for mortality in patients in the third tertile for SII, SIRI, and IPI were 2.32 (1.15–4.67), 3.59 (1.56–8.26), and 4.16 (1.20–14.41), respectively. Incorporating composite inflammatory indicators into the basic model significantly enhanced outcome prediction, with IPI showing the greatest incremental predictive value, as indicated by an increase in C-index (0.042, 95 % CI: 0.004–0.095), a continuous NRI of 0.712 (95 % CI: 0.360–1.063, P < 0.001), and an IDI of 0.010 (95 % CI: 0.001–0.019, P = 0.030). ConclusionsAmong patients with HF, elevated levels of SII, SIRI, and IPI were significantly associated with an increased risk of six-month mortality, with IPI providing the greatest incremental predictive value.

Advances in Immune Biomarkers for Predicting Disease Outcomes and Therapeutic Responses

Advances in Immune Biomarkers for Predicting Disease Outcomes and Therapeutic Responses

Expression of variant isoforms of the tyrosine kinase SYK differentially regulates cervical cancer progression through PI3K/AKT pathway

Invasion and metastasis are the main reasons for the poor prognosis of patients with cervical cancer(CC). SYK is closely related to tumor development. However, the functions of its two isoforms, SYK (L) or SYK (S), are not fully understood to date. In this study, we investigated their biologic functions and possible prognostic values in CC. qRT-PCR was performed to detect the expression of SYK and two variant isoforms in cervical cancer tissues and cells. The association of SYK(L) and SYK(S) with Clinical pathological parameters were evaluated. The migration and invasion was detected by scratch assay and transwell. Western blot was conducted to measure the changes of epithelial mesenchymal transition (EMT)-related markers and PI3K/AKT signaling pathway proteins in cervical cancer cells. LY294002 (inhibitor of PI3K/AKT pathway) and IGF-1 (activator of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in cervical cancer cells. The expression of SYK(S) in cervical cancer tissues was significantly higher than that of SYK(L). SYK(L) and SYK(S) were correlated with muscular infiltration, SYK(L) high expression had a better prognosis, whereas SYK(S) high expression predicted a worse disease outcome. Cox multivariate regression analysis demonstrated that SYK(L) expression was an independent prognostic factor. SYK(L) significantly inhibited the proliferation, migration and invasion, while SYK(S) showed the opposite effects. LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Decision support systems in the diagnosis of urological diseases

The need to process large amounts of data has led to the creation of software that can improve and facilitate the work of medical staff. Decision support systems (DSS) are now used in many branches of medicine both at the outpatient and inpatient stages of medical care, helping clinicians to choose the tactics of treatment and management of each individual patient. These systems to a certain extent can improve treatment results and diagnostic process. The introduction of DSS in clinical practice has shown many advantages in reducing the frequency of misdiagnosis and, consequently, the risk of medical errors. At the same time, DSS can have a number of disadvantages. For example, physicians may view them as a threat to their “clinical autonomy”, and the implementation and subsequent maintenance of DSS can be quite costly. Artificial intelligence, which is increasingly being used not only for diagnosis, but also for treatment and prediction of outcomes in various diseases, should be considered as a prerequisite for the creation of DSS. Active development of artificial intelligence has been noted in almost all branches of medicine. A non-systematic review of the available literature published in the period between 2012 and 2022 has shown that the application of AI in prostate cancer diagnosis has great potential in clinical practice, as it helps both in the choice of treatment method and in planning the course of further surgery.

Clinical characteristics and outcomes of patients on haemodialysis at Jimma medical center, Ethiopia: a 7-Year review

BackgroundHaemodialysis is the primary kidney replacement therapy modality in Africa. In Ethiopia, the number of patients undergoing Haemodialysis is increasing, yet data on their outcomes is scarce. This study assesses the clinical characteristics and outcomes of Haemodialysis patients at Jimma Medical Center.MethodsA retrospective cross-sectional study was conducted from April 08 to 12, 2024, involving patients who underwent Haemodialysis at Jimma Medical Center from June 2017 to March 2024. The data were coded and entered into EpiData version 3.1, then exported to the Statistical Package for Social Sciences version 26.0 for analysis. Descriptive statistics summarized the patients’ clinical characteristics and outcomes, and Kaplan-Meier curves were used to assess survival status.ResultsDuring the seven-year study period, 68 patients underwent Haemodialysis at Jimma Medical Center, with a predominance of males (69.1%). The average age of patients was 42.7 (± 12.8) years with 69.1% (95% CI: 57.5–79.1%) diagnosed with chronic kidney disease, while 30.9% (95% CI: 20.9–42.5%) had acute kidney injury. Among chronic kidney disease patients, common clinical features included nausea and vomiting (100%), proteinuria (95.7%), and body swelling (82.9%), while acute kidney injury patients frequently presented with oliguria (100%), nausea and vomiting (90.5%), and hematuria (52.4%). Hypertensive nephropathy was the leading cause of chronic kidney disease (40.4%), and acute glomerulonephritis (38.1%) and severe malaria (33.3%) were the predominant causes of acute kidney injury. Mortality was observed at 47.6% (95% CI: 27.7–68.6%) in acute kidney injury patients and 40.4% (95% CI: 27.3–54.7%) in chronic kidney disease patients. Emergency vascular access was required in 95.7% of chronic kidney disease and 100% of acute kidney injury patients.ConclusionThis study highlights the substantial burden of chronic kidney disease and acute kidney injury among hemodialysis patients at Jimma Medical Center, revealing distinct clinical profiles and outcomes. Although acute kidney injury patients exhibited a longer median survival time, the significant mortality risk within the first year underscores the urgent need for improved treatment access and resource allocation. Enhancing early intervention and ensuring the availability of critical medications, such as erythropoietin, are essential for optimizing patient outcomes for both chronic kidney disease and acute kidney injury groups.Clinical trial number:Not applicable

UMetals in the Gut: Microbial Strategies to Overcome Nutritional Immunity in the Intestinal Tract.

Trace metals are indispensable nutritional factors for all living organisms. During host-pathogen interactions, they serve as crucial resources that dictate infection outcomes. Accordingly, the host uses a defense strategy known as nutritional immunity, which relies on coordinated metal chelation to mitigate bacterial advances. In response, pathogens employ complex strategies to secure these resources at sites of infection. In the gastrointestinal (GI) tract, the microbiota must also acquire metals for survival, making metals a central line of competition in this complex ecosystem. In this minireview, we outline how bacteria secure iron, zinc, and manganese from the host with a focus on the GI tract. We also reflect on how host dietary changes impact disease outcomes and discuss therapeutic opportunities to target bacterial metal uptake systems. Ultimately, we find that recent discoveries on the dynamics of transition metals at the host-pathogen-microbiota interface have reshaped our understanding of enteric infections and provide insights into virulence strategies, microbial cooperation, and antibacterial strategies.

Parasite-microbiota interactions: a pathway to innovative interventions for Chagas disease, leishmaniasis, and ascariasis.

Parasitic infections are a major global health challenge, driven in part by complex interactions between parasites, host microbiota, and immune responses. Recent advances in microbiome research highlight the critical role of microbiota in influencing disease outcomes and treatment effectiveness. This review examines how changes in the microbiota impact parasite transmission, disease progression, and responses to treatment, focusing on key parasitic diseases such as Chagas disease, leishmaniasis, and ascariasis. The microbiota can either exacerbate or mitigate disease severity, depending on its composition, providing critical insights for novel therapeutic strategies. Emerging approaches discussed include the use of targeted probiotics, prebiotics, and microbiota-modulating drugs to influence parasite dynamics and enhance conventional therapies. The review also explores the potential of integrating microbiota knowledge into vaccine design and immunotherapy, aiming to develop vaccines that elicit stronger immune responses and identify new therapeutic targets. A multidisciplinary approach is essential for translating these findings into effective clinical solutions, with future research focusing on validating microbiota-based interventions in clinical settings. In conclusion, the interaction between microbiota and parasitic infections presents a promising avenue for innovative therapies, with the potential to significantly improve global health outcomes.

Microvascular disease and severe COVID-19 outcomes in UKBiobank participants with diabetes.

Early in the COVID-19 pandemic, evidence emerged suggesting that people with diabetic retinopathy (DR) or other microvascular diseases had greater risk of severe short-term outcomes. This study evaluated longer-term outcomes, providing more generalisable evidence. We identified a cohort of UKBiobank participants with diabetes and retrieved their diagnostic codes for a variety of microvascular diseases, complications of diabetes and systemic comorbidities. We investigated relationships between diagnoses and the study outcome: admission to Critical Care or death from COVID-19, taking age, sex and diabetes duration into account. We tested relationships, adding baseline covariates and weighting diagnostic codes according to their recency prior to COVID-19 diagnosis. In univariate analyses, DR (OR: 1·519, p = 0·016) and microvascular disease (OR: 2·001, p = 0·000) were associated with greater risk of the outcome. In multivariate analyses, as expected, respiratory disease was most strongly associated with the study outcome, microvascular disease second. Adjusting analyses by number of admissions (general health proxy) and weighted diagnostic coding (comorbidity severity at COVID-19 diagnosis indicator), did not improve predictive power of the model. The presence of microvascular disease in routinely-collected healthcare data predicts risk of COVID-19 severe outcomes, independently of general health, in a cohort of people with diabetes.

Olfactory Dysfunction, Dysgeusia, and Clinical Outcomes in COVID-19 Patients: An Observational Study in a Tertiary COVID Referral Center in the Philippines

Objective: To describe the prevalence, onset, associated symptoms, and clinical characteristics of COVID-19 in-patients with olfactory and gustatory dysfunction at the Philippine General Hospital from March 2021 to January 2022 and determine the number of patients with olfactory dysfunction/dysgeusia who recovered or expired. Methods: Design: Prospective Cohort StudySetting: COVID-19 Referral Hospital (Tertiary National University Hospital)Participants: COVID-19 RT-PCR positive in-patients, ages 19 and older Results: A total of 207 patients were included. Sixty-four (64) patients reported olfactory dysfunction and 79 reported dysgeusia. Olfactory and gustatory dysfunction were observed early in the course of infection, before day 6 of illness. The average length of hospital stay was 20.36 days; those with olfactory dysfunction stayed for 17.53 days, dysgeusia for 19.92 days, and 21.09 days for those who noted neither. For those subsequently intubated, 0 had olfactory dysfunction, three reported dysgeusia, three had both and six had neither. Thirteen (13) patients in the study expired. Among them, none reported olfactory dysfunction and two had dysgeusia. Conclusions: Our results corroborate existing literature that olfactory and gustatory dysfunction as key indicators of COVID-19 with 42.5% of participants reporting these symptoms early, often before day 6 of illness. Ninety-two percent (92%) of those affected recovered and had shorter hospital stays, emphasizing the importance of recognizing these dysfunctions for improved disease detection and outcomes.

The FORWARD Psoriasis Registry: Patient-Reported Outcomes in a Novel Psoriasis Registry and Comparison of Traditional, Dermatologist-Led Enrollment With Web-Based Patient Enrollment.

Real-world evidence describing the natural history of all manifestations and severities of psoriasis is needed, as existing studies often recruit from a restricted patient population, and treatment failure and dissatisfaction is common. The FORWARD Psoriasis Registry collects patient-reported data directly online from participants independent of clinician involvement. To test the feasibility of this new registry design and compare baseline characteristics, patient-reported disease outcomes, and treatment utilization between participants enrolling through their clinician (primary enrollment group) and participants self-enrolling online (secondary). We summarized cross-sectional enrollment data from adults with clinician-diagnosed psoriasis who enrolled in the registry from September 2023 through June 2024 and compared baseline characteristics between enrollment groups. The registry enrolled 1560 adults with clinician-diagnosed psoriasis from 42 states and territories in the United States. In the primary enrollment group, 68% were female, mean age was 51years, 34% of participants had moderate or severe psoriasis based on PREPI, and 27% reported clinician-diagnosed psoriatic arthritis. Forty six percent actively used systemic therapies while 65% used topical therapies for psoriasis, and 20% were dissatisfied or very dissatisfied with their treatment. Comparatively, the secondary enrollment group reported statistically significantly worse psoriasis burden for nearly all disease outcomes. The FORWARD Psoriasis Registry rapidly enrolled a large, national cohort of participants with psoriasis, demonstrating feasibility of participant-driven data collection. We found important differences between participants enrolling through their clinician and self-enrolled participants, highlighting the need to collect real-world evidence to understand psoriasis regardless of access to clinical care.

The complement system in lipid-mediated pathologies.

The complement system, a coordinator and facilitator of the innate immune response, plays an essential role in maintaining host homeostasis. It promotes clearance of pathogen- and danger-associated molecular patterns, regulates adaptive immunity, and can modify various metabolic processes such as energy expenditure, lipid metabolism, and glucose homeostasis. In this review, we will focus on the intricate interplay between complement components and lipid metabolism. More precisely, we will display how alterations in the activation and regulation of the complement system affect pathological outcome in lipid-associated diseases, such as atherosclerosis, obesity, metabolic syndrome, age-related macular degeneration, and metabolic dysfunction-associated steatotic liver disease. In addition to that, we will present and evaluate underlying complement-mediated physiological mechanisms, observed both in vitro and in vivo. Our manuscript will demonstrate the clinical significance of the complement system as a bridging figure between innate immunity and lipid homeostasis.

Community-based smart healthcare initiative reduces carotid intima-media thickness and thrombotic markers in patients with hypertension: A prospective study

ObjectiveUnhealthy lifestyles negatively impact the prognosis and outcomes of cardiovascular disease. The objective of this study is to examine the effects of smart healthcare technology in assisting physicians with monitoring and improving patient lifestyles, as well as adjusting treatment plans on carotid intima-media thickness (IMT) and thrombotic markers during the therapeutic management of hypertension. Furthermore, we compared the efficacy of smart healthcare interventions with conventional hospital-based follow-up in ameliorating cardiovascular complications in patients with established hypertension. The goal is to elucidate the optimal timing for clinical interventions and to develop personalized treatment plans to enhance the long-term prognosis of patients with cardiovascular disease. MethodsA stratified sample of 174 patients with established hypertension from two villages in southeastern China was selected. The study cohort comprised 85 participants in the smart healthcare intervention group and 89 participants in the regular follow-up control group. Changes in median levels of IMT, von Willebrand factor (vWF), P-selectin (P-S), body mass index (BMI), blood pressure, and cholesterol were assessed before and after the study period. Comparative analysis of changes in IMT, vWF, P-S, blood pressure, and cholesterol between the two groups was conducted over the study period. ResultsThe intervention group demonstrated significantly greater improvements in IMT, vWF, and P-S levels compared to the control group (P < 0.05). At the 12-month follow-up (T12), blood pressure, BMI, total cholesterol, IMT, P-S, and vWF levels were significantly lower in the intervention group than in the control group (P < 0.05). The reduction in IMT was particularly notable, with the intervention group revealing a statistically significant improvement compared to the control group (P < 0.001). ConclusionThe smart healthcare intervention model resulted in more significant improvements in IMT and thrombotic markers compared to the traditional hospital follow-up model. Patients using the smart blood pressure monitors exhibited significantly lower levels of IMT, vWF, and P-S compared to their pre-intervention levels.

Allostatic load modelling, lifestyle and cardiological risk factor: evidence for integrating patient profiling in the optimisation of pharmacological therapies during follow-ups in hospital setting – PLAY-UP cohort study protocol

IntroductionThe allostatic load (AL) is a framework for conceptualising the physiological multisystemic impact of prolonged exposure to stress and its related side effects on mental health.Stress due to AL can...

Impact of Ramadan fasting on kidney function and related outcomes in chronic kidney disease and kidney transplant recipients: a systematic review and meta-analysis

ObjectivesRamadan fasting is an Islamic religious practice involving abstinence from food and drink from dawn to sunset. Its consequences on kidney-relevant outcomes in patients with chronic kidney disease (CKD) and...

A comprehensive review of patient-reported outcomes in metabolic dysfunction-associated steatotic liver disease

The global prevalence of obesity and type 2 diabetes has increased, contributing to an increased worldwide prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Currently, one in three adults is affected by MASLD and/or its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), making this liver disease a significant public health challenge. Along with MASH-related cirrhosis, these conditions are poised to become the leading causes of chronic liver disease and liver transplants in the near future. Given the growing burden of MASLD and MASH, it is crucial to understand their impact from the patients’ perspective. One way to do this is by assessing patient-reported outcomes (PROs), including health-related quality of life (HRQL). HRQL can be assessed using generic instruments like the short form 36 version (SF-36) and the European quality of life-5 dimensions questionnaire (EQ-5D), or disease-specific tools such as the chronic liver disease questionnaire for nonalcoholic steatohepatitis (CLDQ-NASH). Given the limitations of each instrument, the best approach generally involves using both generic and disease-specific instruments. Evidence indicates that HRQL scores are significantly lower in individuals with MASLD, especially in areas assessing physical activity and the ability to perform daily living tasks. Fatigue and impaired work productivity are also important PROs for those with MASLD/MASH. These decrements in PROs worsen with disease progression but appear to improve with disease regression, including improvements linked to treatment. In this context, measuring PROs enhances the assessment of other patient-centric outcomes and provides insights for the healthcare community to develop interventions that could improve both clinical and humanistic outcomes for individuals living with MASLD/MASH.

Artificial intelligence systems for predicting chronic ischemic heart disease outcomes in cardiac surgery patients based on presence of anemia: a literature review

BACKGROUND: In Russia, the number of people undergoing heart surgery exceeds 600 thousand annually. These include anemia in 30–70% of patients with a 4-fold increased risk of one-year death, a 5-fold increased risk of stent thrombosis, a 1.3-fold increased risk of recurrent acute coronary events, and a 2-fold increased risk of bleeding. However, among the prognostic systems developed using artificial intelligence (AI) technologies, few take the presence of anemia into account. Existing digital platforms are not designed to support clinical decision making. AIM: The review aimed to evaluate existing AI platforms for predicting the course of ischemic heart disease (IHD) and systems that take into account the presence of anemia. MATERIALS AND METHOD: The PubMed and Russian Science Citation Index databases from 2000 to January 2024 were analyzed. Using Keywords of “artificial intelligence”, “anemia”, “coronary heart disease”, “hemoglobin”, and “cardiac surgery”, 906 articles were found, of which 38 met the inclusion criteria for analysis. RESULTS: In some countries, AI platforms have been created to predict the course of IHD. This review analyzes published data on the development and use of AI-based digital products for the management of patients with IHD, including those that take into account key hemodynamic parameters. CONCLUSION: Analysis of existing developments revealed a focus on solving prognostic problems. However, in our opinion, the range of parameters analyzed is not wide enough. For example, anemia, which plays a key role in modifying the risk of adverse outcomes in IHD, has not been considered as a factor.

Genetic Insights into Therapeutic Targets for Neuromyelitis Optica Spectrum Disorders: A Mendelian Randomization Study.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe central nervous system disease primarily characterized by optic neuritis and myelitis, which can result in vision loss and limb paralysis. Current treatment options are limited in their ability to prevent relapses and mitigate disease progression, underscoring the urgent need for new drug targets to develop more effective therapies. The objective of this study is to identify potential drug targets associated with a reduced risk of NMOSD attacks or relapses through Mendelian randomization (MR) analysis, thereby addressing the limitations of existing treatment methods and providing better clinical options for patients. To identify therapeutic targets for NMOSD, a MR analysis was conducted. The cis-expression quantitative trait loci (cis-eQTL, exposure) data were sourced from the eQTLGen consortium, which included a sample size of 31,684. NMOSD (outcome) summary data were obtained from two of the largest independent cohorts: one cohort consisted of 86 NMOSD cases and 460 controls derived from whole-genome sequencing data, while the other cohort included 129 NMOSD patients and 784 controls. We performed a two-sample MR analysis to evaluate the association between single nucleotide polymorphisms (SNPs) and copy number variations with NMOSD. The MR analysis utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses were conducted to assess the presence of horizontal pleiotropy and heterogeneity. Colocalization analysis was employed to test whether NMOSD risk and gene expression are driven by common SNPs. Additionally, a phenome-wide association study (PheWAS) was performed to detect disease outcomes associated with NEU1. Supplementary analyses included single-nucleus RNA sequencing (snRNA-seq) data analysis, protein-protein interaction (PPI) networks, and drug feasibility assessments to prioritize potential therapeutic targets. Two drug targets, COL4A1 and NEU1, demonstrated significant MR results in two independent datasets. Notably, NEU1 showed substantial evidence of colocalization with NMOSD. Additionally, apart from the association between NEU1 and NMOSD, no other associations were observed between gene-proxied NEU1 inhibition and the increased risk of other NMOSD-related diseases. This study supports the potential of targeting NEU1 for drug inhibition to reduce the risk of NMOSD. Further preclinical research and drug development are warranted to validate the efficacy and safety of NEU1 as a therapeutic target and to explore its potential in NMOSD treatment.

Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) as a Biomarker of Cardiovascular Disease.

Insulin-like growth factor-binding protein-1 (IGFBP-1) contributes to the regulation of IGFs for metabolism and growth and has IGF-independent actions. IGFBP-1 in the circulation is derived from the liver, where it is inhibited by insulin and stimulated by multiple factors, including proinflammatory cytokines. IGFBP-1 levels are influenced by sex and age, which also determine cardiometabolic risk and patterns of disease presentation. While lower circulating IGFBP-1 concentrations are associated with an unfavorable cardiometabolic risk profile, higher IGFBP-1 predicts worse cardiovascular disease outcomes. This review explores these associations and the possible roles of IGFBP-1 in the pathophysiology of atherosclerosis. We recommend the evaluation of dynamic approaches, such as simultaneous measurements of fasting IGFBP-1 and proinsulin level in response to an oral glucose challenge, as well as multi-marker approaches incorporating markers of inflammation.