Clinical Implications Research Articles

Deterioration Patterns in Patients Admitted for Severe COPD Exacerbation

Background: Chronic obstructive pulmonary disease (COPD) exacerbations represent significant clinical events marked by worsening respiratory symptoms, often necessitating changes in medication or hospitalization. Identifying patterns of exacerbation and understanding their clinical implications are critical for improving patient outcomes. This study aimed to identify exacerbation patterns in COPD patients using variations in the COPD Assessment Test (CAT) scores and compare clinical characteristics and comorbidities among patients with different exacerbation patterns. Methods: An observational study was conducted involving COPD patients admitted for severe exacerbations. The administered CAT questionnaire referred to two periods: 1) the period during hospital admission and 2) the stable period two months prior to admission. Results: Fifty patients (60% male, mean age 70.5 years, standard deviation [SD] 9.6) were included; of these, eight (16%) were active smokers. Significant worsening in CAT scores during the exacerbation compared to the stable period was observed (25 vs. 13.5, p < 0.001). Three exacerbation patterns were identified: increased cough and sputum (cluster 1); increased dyspnea and activity limitation (cluster 2); and poorer sleep quality and lower energy (cluster 3). No significant differences were found regarding demographics and lung function. Conclusions: Three distinct exacerbation patterns were identified in COPD patients based on CAT score variations, suggesting that exacerbations are heterogeneous events. Future studies with larger sample sizes and prospective follow-up are necessary to validate these findings and explore their clinical and prognostic implications.

Saliva-based point-of-care assay to measure the concentration of pyrazinamide using a mobile UV spectrophotometer

Abstract Introduction Pyrazinamide, one of the first-line antituberculosis drugs, displays variability in drug exposure that is associated with treatment response. A simple, low-cost assay may be helpful to optimize treatment. This study aimed to develop and validate a point-of-care assay to quantify the concentration of pyrazinamide in saliva. Methods All measurements were conducted using the nano-volume drop function on the mobile ultraviolet (UV) spectrophotometer (NP80, Implen, Germany). Assay development involved applying second derivative spectroscopy in combination with the Savitzky–Golay filter between wavelengths of 200–300 nm to increase spectral resolution. Assay validation included assessing selectivity, linearity, accuracy, precision, carry-over and matrix effects. Specificity was also analysed by evaluating the impact of co-administered medications on pyrazinamide results. Sample stability was measured at various temperatures up to 40°C. Results The calibration curve (7.5–200 mg/L) was linear (R2 = 0.9991). The overall accuracy (bias%) and precision (CV%) ranged from −0.66% to 5.15%, and 0.56% to 4.95%, respectively. Carry-over and matrix effects were both acceptable with a bias% of <±4% and CV% of <7.5%. Commonly co-administered medications displayed negligible interferences. Levofloxacin displayed analytical interference (bias% = −10.21%) at pyrazinamide concentrations < 25 mg/L, but this will have little clinical implications. Pyrazinamide was considered stable in saliva after 7 days in all storage conditions with a CV% of <6.5% and bias% of <±10.5% for both low- and high-quality control concentrations. Conclusions A saliva-based assay for pyrazinamide has been successfully developed and validated using the mobile UV spectrophotometer.

Stent thrombosis in the setting of ST-segment elevation acute myocardial infarction in the contemporary practice: results from the TOTAL randomized trial.

The aim was to know the risk and predictive factors of stent thrombosis (ST) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in the contemporary practice. The TOTAL [ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone] randomized trial, being the largest trial performed in the setting of STEMI with a general application of the recent recommendations, represents a unique opportunity to know the current real-world incidence of ST as well as its associated factors. A total of 10 064 patients that received ≥1 coronary stent in the TOTAL trial comprise the study population. The risk, predictive factors, and clinical implications of ST was studied. During 1-year follow-up, 155 patients (1.54%) suffered definitive or probable ST (59 acute, 67 subacute, and 29 late). Previous infarction, the number of stents, the previous use of clopidogrel, and the use of diuretics at discharge were independent predictors for ST, whereas the use of upfront glycoprotein IIb/IIIa inhibitors, radial access, and treatment with statins at discharge were independent protective factors. The number of stents, stent diameter, upfront treatment with IIb/IIIa inhibitors, previous treatment with clopidogrel, and treatment with statins at discharge were independently associated with the risk of early ST. Only previous infarction was associated with the risk of late ST. In the contemporary practice, ST still constitutes a frequent complication of primary PCI for STEMI, occurring in 1.5% of patients. Independent predictors are different depending on the time of ST.

Recent developments in immunotherapy approaches for allergic rhinitis.

Allergic rhinitis (AR) poses a significant global health burden, with the potential to progress to asthma, thereby impacting patients' quality of life. Immunotherapy has demonstrated effectiveness in mitigating clinical symptoms by altering the underlying disease mechanisms of AR. This article provides a thorough review of the current state of immunotherapy for AR, encompassing various facets of immunotherapeutic strategies, elucidating their mechanisms and clinical implications. By presenting a nuanced understanding of the present landscape of immunotherapy for AR, this review aims to serve as a valuable reference for informing clinical treatment strategies. The subsequent analysis of diverse immunotherapeutic pathways offers a comprehensive understanding of their mechanisms and clinical implications. A meticulous examination is conducted on subcutaneous immunotherapy, sublingual immunotherapy, oral immunotherapy, intralymphatic immunotherapy, and innovative intravenous gold-induced autologous serum injection therapy. Each pathway is systematically elucidated, with its distinctive features and potential contributions to managing AR emphasized. In conclusion, synthesizing epidemiological insights, immunotherapeutic nuances, and pathway-specific analyses encapsulates a profound understanding of immunotherapy for AR.

Novel factors affecting fibrin clot formation and their clinical implications.

Fibrin formation is pivotal in hemostasis, serving as a temporary barrier to blood loss following vascular injury, while in thrombosis this process is involved in thrombus progression, stability, and recurrence. Growing evidence shows an exceptional complexity of processes that determine fibrin clot structure and function, especially lysability, both in health and disease, which might be relevant in the pathogenesis of arterial and venous thromboembolic diseases. In this overview we summarized available data on novel factors that in recent years have been suggested to contribute to prothrombotic fibrin clot properties, involving formation of compact fibrin networks (reduced clot permeability) displaying impaired susceptibility to lysis (prolonged clot lysis time). The factors discussed in this review encompass elevated levels of factor (F)XI, and its activated form (FXIa), protein carbonylation as the most common type of post-translational modification, neutrophil extracellular traps (NETs) formation, increased levels of circulating lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, along with antithrombin deficiency. These factors have been shown to be not only associated with ischemic stroke, myocardial infarction, pulmonary embolism, and cardiovascular death, but also with unfavorably altered fibrin clot characteristics, which underscores clinical relevance of fibrin clot properties. Given preclinical or ongoing studies aimed at modifying some of these factors, in particular FXI / FXIa inhibitors, recent findings might expand our knowledge on fibrin-related mechanisms of emerging therapeutic agents tested and stimulate further research into new targets for future therapeutic interventions to prevent thromboembolic events.

Identifying the genetic association between severe autoimmune type 2 diabetes and the risk of focal epilepsy

BackgroundObservational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomization (TSMR) method.MethodsGenetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensitivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform.ResultsFor forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs.DiscussionThis MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor.

Prognostic significance of fibrinogen levels in sepsis-associated acute kidney injury: unveiling a nonlinear relationship and clinical implications

BackgroundFibrinogen plays a pivotal role in the inflammatory cascade and is intricately linked to the pathogenesis of sepsis. Nevertheless, its significance as a prognostic marker for sepsis-associated acute kidney injury (SA-AKI) remains uncertain. This study aimed to investigate the association between fibrinogen levels and 28-day mortality with sepsis-associated acute kidney injury.MethodThe fibrinogen levels of patients admitted to the intensive care unit of Beth Israel Deaconess Medical Center between 2008 and 2019 were retrospectively assessed, and those diagnosed with SA-AKI were divided into low, middle and high fibrinogen level groups according to tertiles. Multivariate Cox proportional hazards model was used to assess the 28-day mortality risk of the SA-AKI patients.ResultsA total of 3,479 patients with SA-AKI were included in the study. Fibrinogen demonstrated an independent association with 28-day mortality, yielding a hazard ratio (HR) of 0.961 (95% confidence interval [CI]: 0.923-0.999, P = 0.0471). Notably, a non-linear relationship between fibrinogen levels and 28-day mortality was observed, with the threshold observed at approximately 1.6 g/l. The effect sizes and corresponding CIs below and above this threshold were 0.509 (0.367, 0.707) and 1.011 (0.961, 1.064), respectively. Specifically, the risk of mortality among SA-AKI patients decreased by 49.1% for every 1 g/l increment in fibrinogen, provided that fibrinogen levels were less than 1.6 g/l.ConclusionIn patients with SA-AKI, a non-linear relationship was identified between fibrinogen levels and 28-day mortality. Particularly, when their fibrinogen levels were less than 1.6 g/l, a concomitant decrease in 28-day mortality was observed as fibrinogen levels increased.

The vague language use scale: Clinical utility and psychometrics from adults with traumatic brain injury.

Pragmatic communication difficulties encompass many distinct behaviours, including the use of vague and/or insufficient language, a common characteristic following traumatic brain injury (TBI) that negatively impacts psychosocial outcomes. Existing assessments evaluate pragmatic communication broadly, often with only one or two items capturing each behaviour, thus limiting sensitivity and precision to variations within each behaviour. Given that greater nuance is needed to detect subtle pragmatic communication differences and investigate underlying cognitive mechanisms, a more refined measure is critical to improve psychosocial outcomes. The Vague scale was developed to address those needs. To provide preliminary evidence supporting the novel Vague language use (Vague) scale's reliability, validity and clinical utility. The Vague scale rates each discourse sample utterance for vague language use on a 3-point scale; the measure's Vague score represents the mean of utterance-level ratings. Using the Vague scale, two raters naïve to diagnosis evaluated Cinderella narratives of 46 adults with severe TBI and 46 controls with no brain injury, providing reliability, construct validity and classification accuracy evidence. Vague scores were also compared to other clinical measures to gather criterion-related validity evidence. Interrater agreement across all transcripts was moderate. Construct validity was supported by expected group differences and criterion validation, including significant relationships with increased violations of Grice's maxim of quantity and measures of lexical variation; significant relationships with psychosocial outcomes, supporting clinical utility; and nonsignificant relationships with measures of syntax and overall pragmatic communication. Classification accuracy expectedly did not support using Vague scores in isolation for diagnosis, due to unacceptable sensitivity (0.696). Evidence supported the Vague scores' psychometric properties. Thus, the Vague scale shows promise as a measure of one distinct pragmatic communication behaviour: vague language use. Future research should apply the Vague scale to determine its sensitivity in individuals with subtle social communication challenges (e.g., mild TBI), explore its utility with more naturalistic discourse samples as part of a pragmatic communication battery, longitudinally examine changes in Vague scores, and investigate cognitive mechanisms underlying this specific pragmatic communication behaviour. What is already known on this subject Use of vague language is common following traumatic brain injury (TBI) and may contribute to negative psychosocial outcomes related to employment and relationships. However, existing measures of vague language lack sensitivity and precision, limiting their utility for identifying subtle performance variations or determining the cognitive mechanisms underlying this specific pragmatic communication behaviour. What this study adds to existing knowledge The current study gathered promising reliability, validity and clinical utility evidence to support using the novel Vague language use (Vague) scale, which was developed to address these limitations. Based on complex (Cinderella) stories of adults with and without TBI, Vague scores demonstrated moderate interrater agreement and promising construct validity based on expected group differences and criterion validation, including moderate associations with related constructs and weak associations with unrelated constructs. Because pragmatic communication profiles post-TBI can vary, classification accuracy expectedly indicated that Vague scores should not be used alone to identify communication differences post-TBI. What are the clinical implications of this work? Vague scores show promise for documenting clients' use of vague language and planning intervention to address associated discourse-level challenges. Future research should investigate applying the Vague scale to naturalistic discourse samples (1) as part of a battery that sensitively and precisely identifies pragmatic communication differences and (2) as a tool for investigating cognitive mechanisms underlying vague language use, with the goal of improving interventions that support pragmatic communication and enhance psychosocial outcomes.

Gender differences in internet gaming among university students: a discriminant analysis

IntroductionResearch on gaming and gaming habits has predominantly focused on younger populations, particularly males. The main objective of this study was to analyze gender-based differences in gamer profiles, considering variables related to gaming habits and the gaming community.MethodsA total of 180 Spanish university students currently engaged in video gaming (M = 21.51 years, SD = 3.09, 57.4% male) participated in the study by completing an online questionnaire addressing gaming characteristics such as the age of onset, gaming hours, motives of gaming, and perceived toxicity in the video gaming community.ResultsThe results revealed statistically significant gender differences in the age of gaming initiation, weekly gaming hours, community toxicity, and several gaming motivations, including customization, cognitive challenge, violent gratification, and social interaction. Linear discriminant analysis identified that higher scores in the age of initiation and customization, along with lower scores in violent gratification and community toxicity, formed the combination of predictor variables that most strongly distinguished between genders.ConclusionUnderstanding these gender differences is essential for capturing current gaming trends and addressing the needs of diverse gamers. Finally, the potential clinical implications of these findings are discussed.

Chest computed tomography-based artificial intelligence-aided latent class analysis for diagnosis of severe pneumonia.

There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA). This retrospective study included 413 patients hospitalized at Xinhua hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods. The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections (P <0.001) than patients with subphenotype-2 and had lower 30-day (P <0.001) and 90-day (P <0.001) mortality, and lower in-hospital (P=0.001) and 2-year (P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes (P<0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment. A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.

Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials

With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

Comprehensive Guide to Paravalvular Leak: Symptoms, Effects, and Treatments.

Paravalvular leak (PVL) represents a common complication often encountered following valve replacement surgeries, posing significant diagnostic and therapeutic challenges within the field of cardiology. The condition, characterized by an abnormal flow of blood around the edges of a prosthetic valve, can lead to a spectrum of clinical manifestations, from asymptomatic states to severe heart failure or hemolysis. Its relevance is underscored by its contribution to morbidity and mortality among affected individuals, necessitating a deeper understanding of its etiology, diagnosis, and management. The exploration of advanced diagnostic tools, such as echocardiography, computed tomography, and magnetic resonance, alongside novel treatment approaches, underscores the dynamic and evolving landscape of PVL management. This is a concentrated guide to understand the various aspects related to PVL, starting with defining the condition to determine its short- and long-term effects on the patient. It will further direct the reader through diagnosis, going through the advancements made in cardiac imaging, especially three-dimensional modeling and echocardiography. The discussion of predisposing factors, technical considerations intrinsic to procedural interventions, and clinical implications is therefore an important part of the discourse and helps set a foundation for an in-depth exploration of contemporary and emerging treatment modalities. From the incorporation of various surgical and percutaneous techniques to the tactical uses of devices, in particular, the AMPLATZer Vascular Plug, associated with the technical development of transcatheter closure, the current review tries to present a panoramic view of PVL management, from diagnosis to closure and insight into mitigation of its impact on outcomes.

Left Atrial Strain: State of the Art and Clinical Implications

The assessment of left atrial strain (LAS) has emerged as an essential component in the evaluation of cardiac function, especially in pathologies such as heart failure and atrial fibrillation. This narrative review aims to outline the available methods for assessing LAS with a major emphasis on speckle-tracking echocardiography techniques. Other imaging modalities, including cardiac magnetic resonance and cardiac computed tomography, also provide important information on LA dynamics but have disadvantages with respect to cost and availability. The current narrative review underlines basic concepts such as the accurate assessment of LAS and discusses the clinical relevance of LAS by pointing out its significant diagnostic and prognostic role in several cardiovascular conditions. The aim of this article is to discuss the current integration of LAS into clinical practice with a view to further improving patient management and treatment strategies.

Effects of social interaction on leisure item preference and reinforcer efficacy for children with autism.

We replicated and extended Kanaman et al. (2022) by comparing outcomes of solitary (leisure items only), social (leisure items with social interaction), and combined (leisure items alone and leisure items with social interaction) stimulus preference assessments to determine the extent to which the inclusion of social interaction influenced the outcomes of preference assessments for five children with autism. We then conducted reinforcer assessments to determine the reinforcing efficacy of high- and low-preferred leisure items when presented with and without social interaction. The results showed that both high- and low-preferred items functioned as reinforcers to varying degrees for all participants and the inclusion of social interaction increased the reinforcing efficacy of some items for all participants. Additionally, the results showed that combined preference assessments predicted reinforcer assessment outcomes for two of five participants but produced false-negative outcomes for three participants. Clinical implications and directions for future research are discussed.

Association between different proportions of crescents and the progression of IgA nephropathy (IgAN): a systematic review and meta-analysis.

Immunoglobulin A nephropathy (IgAN) is a complex renal disease with a highly variable clinical course. Identifying reliable prognostic markers is crucial for risk stratification and treatment decisions. This study aimed to understand the influence of different proportions of crescents (Cs) on the progression of IgAN. Four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched until September 25, 2023. The study encompassed IgAN patients, focusing on kidney outcomes and end-stage kidney disease (ESKD). Statistical analysis included calculating hazard ratios (HR) for binary outcomes and examining publication bias. The meta-analysis involved thirteen studies comprising 11,849 patients. For kidney outcomes, crescent formation may be linked to an elevated risk (HR = 2.01, 95%CI 1.40-2.87, P < 0.001). Furthermore, significantly increased risks of kidney outcomes were observed with a crescent proportion > 10 (HR = 1.8, 95%CI 1.32-2.45, P < 0.001) and > 25%(HR = 2.11, 95% CI 1.47-3.02, P < 0.001). Regarding ESKD, a proportion > 25% also displayed an elevated risk (HR = 1.70, 95% CI 1.18-2.44, P = 0.004). However, a proportion > 10% (including > 25%) did not show a significant association with ESKD (HR = 1.12, 95% CI 0.36-3.47, P = 0.842) versus less. This systematic review and meta-analysis established a strong association between crescent proportions and the progression of IgAN. Higher proportions, notably exceeding 25%, were reliable prognostic markers, indicating a greater risk of adverse kidney outcomes and ESKD. These findings have significant clinical implications, offering the potential for more precise risk stratification in IgAN patients.

The Genetic Basis of Non-Contact Soft Tissue Injuries-Are There Practical Applications of Genetic Knowledge?

Physical activity increases the risk of non-contact injuries, mainly affecting muscles, tendons, and ligaments. Genetic factors are recognized as contributing to susceptibility to different types of soft tissue injuries, making this broad condition a complicated multifactorial entity. Understanding genetic predisposition seems to offer the potential for personalized injury prevention and improved recovery strategies. The candidate gene analysis approach used so far, has often yielded inconclusive results. This manuscript reviews the most commonly studied genetic variants in genes involved in the musculoskeletal system’s structure and recovery processes (ACTN3, ACE, CKM, MLCK, AMPD1, IGF2, IL6, TNFα, CCL2, COL1A1, COL5A1, MMP3, and TNC). Referring to the literature, it was highlighted that single-gene analyses provide limited insight. On the other hand, novel genetic testing methods identify numerous variants of uncertain physiological relevance. Distinguishing between functionally important variants, modifying variants, and the thousands of irrelevant variants requires advanced bioinformatics methods and basic multiomics research to identify the key biological pathways contributing to injury susceptibility. Tools like the Total Genotype Score (TGS) and Polygenic Risk Score (PRS) offer a more holistic view by assessing the combined effect of multiple variants. However, these methods, while useful in research, lack clinical applicability. In conclusion, it is too early to determine the clinical implications of genetic variability as a tool for improving well-established training and injury prevention methods, as the predictive power of genetic testing for injury predisposition is currently low.

Perceptions of Overall Health Differences Among Veterans Across Marital Statuses.

We examined the relationship between substance use, marital status, and perceived overall health using national data from a sample of 1,506 retired active-duty veterans. We found that binge drinking and heavy alcohol use among widowed veterans have a negative effect on overall health compared to married veterans who did not use alcohol in the past month. We found that non-binge and binge drinking have a positive effect on perceptions of overall health among divorced or separated veterans compared to those who are married and did not use alcohol in the past month. We discuss these findings and address clinical implications.

Carotid Artery Geometry Modifications and Clinical Implications after Carotid Artery Stenting

Background: Carotid artery stenting (CAS) could lead to a modification of the carotid bifurcation geometry with possible clinical implications. This study aimed to clarify the geometrical impact of three carotid stents with different designs on the carotid bifurcation and its clinical consequences. Methods: This was a retrospective single-center study. We included all patients who underwent CAS in a 3-year period. Anatomical changes of the carotid bifurcation were evaluated by reviewing angiographic images. The population was divided into three groups based on the stent implanted: Group 1 (Carotid Wallstent), Group 2 (Roadsaver), and Group 3 (C-Guard). Results: A total of 226 patients were included. The mean age was 77.0 ± 7.4 years and 72.5% (164/226) were male. Three different stents were implanted into three groups: Group 1 (n = 131/226, 58%), Group 2 (n = 57/226, 25.2%), and Group 3 (n = 38/226, 16.8%). The mean pre-stent implantation CCA-ICA angle of the entire population was 155 ± 14.9°, and the post-CAS angle was 167.7 ± 8.7° (p = 0.0001). In every subgroup, the difference was statistically different, with the biggest difference registered in Group 2 (−16.1 ± 13.2°). Regarding stent oversizing, there was a significant relationship between CCA oversizing and CCA-ICA angle modification (p = 0.006). During follow-up, a total of 14 (6.2%) restenoses were registered. The mean CCA-ICA angle modification in the restenosis group was −9.5 ± 14.4° vs. −12.8 ± 11.9° in the no-restenosis group with no significant statistical differences were outlined (p = 0.3). Conclusions: Compared to the Carotid Wallstent and C-Guard, the Roadsaver stent appears to have a lower adaptability to the carotid vascular territory, resulting in a higher CCA-ICA angle modification after implantation, with no impact on the stent restenosis rate.

Appraising the life-course impact of Epstein-Barr virus exposure and its genetic signature on periodontitis.

Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein-Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown. Within a life-course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross-trait genetic correlations, followed by transcriptome-wide association and enrichment analysis to discern the genetic-phenotypic biological profiles. Heightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09-1.47],p=6.05×10-3) and demonstrate a significant genetic correlation (p=4.11×10-3). This pathogenesis may involve the high-confidence causal gene RNASEK located in 17p13.1. Genetically predicted early-life anti-EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82-0.97],p=1.76×10-3). The present study highlights the impact of life-course EBV exposure and its genetic hallmark on periodontitis, providing novel perspectives into the underlying pathogenesis and management strategies for EBV-related periodontitis. These findings underscore diverse clinical and public health implications, encompassing antiviral therapies, viral vaccination strategies, and tailored interventions for individualized periodontitis management. Further research is required to validate and expand upon our findings. Periodontitis is a chronic inflammatory disease driven by interactions between microbial pathogens and the host immune system. While bacteria have traditionally been the focus of research, recent studies highlight the significance of virus-bacteria interactions, particularly the role of Epstein-Barr virus (EBV)-a herpesvirus infecting over 90% of the global population-in the development of periodontitis. However, the underlying causal and genetic mechanisms remain unclear. Our study employed genome-wide multi-omics approaches to investigate the link between EBV exposure and periodontitis. We found that recent EBV infection or reactivation increases the risk of periodontitis, whereas early-life exposure, possibly enabling immune resistance, may reduce it. Essential genes were identified as potential mediators, including CRTC3-AS1, HLA-DQA1, and RNASEK. These findings provide novel insights into the EBV-periodontitis connection. For example, viral testing and control could benefit patients unresponsive to standard bacterial treatments, and early viral exposure via vaccination might reduce the risk of periodontitis. Further clinical studies are required to elucidate these underlying mechanisms and the contribution of virus-bacteria interactions.

Germline natural killer cell receptors modulating the T cell response

In addition to their central role during innate responses, NK cells regulate adaptive immunity through various mechanisms. A wide array of innate receptors has been involved in the NK cell regulatory function. However, the clinical implications of these regulatory pathways are poorly understood. Here, we review the experimental evidence on the effects of NK cells on T cells and their positive and negative consequences for disease outcome during T cell responses in humans.