Disease Severity Research Articles

Cardiovascular Risk Estimation and Stratification Among Individuals with Hypercholesterolemia.

This review aims to assess the variability in considering hypercholesterolemia for cardiovascular risk stratification in the general population. Recent literature on the integration of hypercholesterolemia into clinical risk scores and its interaction with other risk factors will be explored. The impact of hypercholesterolemia on risk estimation varies among different cardiovascular risk calculators. Elevated lipid levels during early life stages contribute to atherosclerotic plaque development, influencing disease severity despite later treatment initiation. The interplay between low-density lipoprotein cholesterol (LDLc), inflammatory markers and non-LDL lipid parameters enhances cardiovascular risk stratification. Studies have also examined the role of coronary artery calcium (CAC) score as a negative risk marker in populations with severe hypercholesterolemia. Furthermore, polygenic risk scores (PRS) may aid in diagnosing non-monogenic hypercholesterolemia, refining cardiovascular risk stratification and guiding lipid-lowering therapy strategies. Understanding the heterogeneity in risk estimation and the role of emerging biomarkers and imaging techniques is crucial for optimizing cardiovascular risk prediction and guiding personalized treatment strategies in individuals with hypercholesterolemia.

Potential Role of Oxidative Stress in the Pathophysiology of Neurodegenerative Disorders.

Neurodegeneration causes premature death in the peripheral and central nervous system. Neurodegeneration leads to the accumulation of oxidative stress, inflammatory responses, and the generation of free radicals responsible for nervous disorders like amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders. Therefore, focus must be diverted towards treating and managing these disorders, as it is very challenging. Furthermore, effective therapies are also lacking, so the growing interest of the global market must be inclined towards developing newer therapeutic approaches that can intercept the progression of neurodegeneration. Emerging evidences of research findings suggest that antioxidant therapy has significant potential in modulating disease phenotypes. This makes them promising candidates for further investigation. This review focuses on the role of oxidative stress and reactive oxygen species in the pathological mechanisms of various neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders and their neuroprotection. Additionally, it highlights the potential of antioxidant-based therapeutics in mitigating disease severity in humans and improving patient compliance. Ongoing extensive global research further sheds light on exploring new therapeutic targets for a deeper understanding of disease mechanisms in the field of medicine and biology targeting neurogenerative disorders.

Association of Platelet Count with Severity of Chronic Liver Disease

Introduction: Chronic liver disease (CLD) is a significant global health concern, encompassing a range of liver pathologies with varying degrees of severity. This cross- sectional study aims to investigate the relationship between platelet count and the severity of CLD. Platelet count is a readily available and cost-effective clinical parameter that may serve as a valuable prognostic marker for CLD progression.  Materials and Method: The study included 122 patients in Chitwan Medical College Teaching Hospital (CMCTH) diagnosed with CLD during one year starting from March 2022. Data were collected using the proforma specially designed for this study. Parameters like age and gender, as well as brief clinical data, including liver function tests, imaging findings, and platelet count, were collected. Patients were then classified into different stages of severity based on established criteria, i.e. child Pugh Score system (CTP score). Statistical analyses were performed using a statistical package for the social science (SPSS); statistical program version 20.0, to explore the association between platelet count and CLD severity.  Results: The majority of patients who had chronic liver disease were found to be high in the age group of 40-60 years. Thrombocytopenia was found in 72.1% of chronic liver disease patients. After classifying the severity of chronic liver disease, it was found that 55.7% of patients had a severe disease that was CTP-C, 36.1% were found to be CTP-B and 8.2% were CTP-A. In patients with normal platelet count, 44.1% had CTP-B, 41.2 had CTPC and 14.7% had CTP-A score. In patients with thrombocytopenia, 61.4% had CTP-C, 33.0% had CTP- B and 5.7% had CTP-A score.  Conclusion: This study provides a valuable snapshot of the potential association between platelet count and the severity of chronic liver disease. The prevalence of thrombocytopenia across different disease stages underscores its clinical relevance. The platelet count is decreased in chronic liver disease, however, it cannot be defined as the sole predictor for the severity of CLD.

Natural History and Longitudinal Outcomes of Patients with Mild-to-Moderate Ulcerative Proctitis or Ulcerative Proctosigmoiditis: A Single-Center, Retrospective Study.

Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied. The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3years. A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up. A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients. Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.

Relation between aeroallergen sensitization and disease severity in asthmatic natives of tropical Kerala - the RADIANT asthma study.

Relation between aeroallergen sensitization and disease severity in asthmatic natives of tropical Kerala - the RADIANT asthma study.

Assessment of obstructive airway disease in the multicenter SWORD survey India.

The study aimed to assess the control of asthma and the severity of chronic obstructive pulmonary disease (COPD) and evaluate the adequacy of treatment in patients presenting to the outpatient department (OPD) across India. The secondary aim was to assess the risk factors associated with poorly controlled asthma and severe COPD. This is the analysis of Phase IV of the multicenter questionnaire-based point prevalence SWORD survey, conducted in May 2018, and designed to capture details on disease control and treatment as per the global initiative for asthma and the global initiative for chronic obstructive lung disease guidelines. Of the 5,311 respiratory disease patients presenting to the OPD, there were 1,419 and 412 patients with asthma and COPD, respectively, across 290 sites in India. There were 1,022 (72%) patients having well-controlled asthma, 293 (20.6%) patients with partly controlled asthma, and 104 (7.4%) patients with poorly controlled asthma. Of the 412 patients with COPD, there were 307 (74.5%) in A, 54 (13.1%) in B, and 51 (12.4%) in the E category. In spite of poor control or severe disease, 34.8% of asthmatic and 25.7% of patients in the B and E categories of COPD were not using any medicine. Risk factors for partly and poorly controlled asthma included rain wetting (adjusted odds ratio [AOR]: 1.59, 95% confidence interval [CI]: 1.02-2.47) and gastroesophageal reflux disease (AOR: 1.50, 95%CI: 1.08-2.10). This study identifies a gap in the treatment of both poorly controlled asthma and severe COPD. A substantial number of patients had poorly controlled asthma and severe COPD, and many were either not taking treatment or taking it inappropriately.

Periodontal health in patients with type 1 diabetes mellitus: relationship and risk factors of periodontitis progression

The article presents the results of literary sources review, namely clinical and experimental studies, meta-analyses and systematic analyzes regarding the effect of type 1 diabetes (T1D) on the periodontal tissues. According to them, the prevalence of periodontitis in patients with T1D is probably higher compared to healthy people. However, there are conflicting data on the cause-and-effect relationship between T1D and periodontitis. The article analyzes the impact of metabolic control in patients with T1D on the severity of periodontal diseases and the clinical attachment loss. Most studies show that the level of metabolic control of diabetes is associated with a high risk of developing periodontitis. The authors provide data from the analysis of the literature on possible mechanisms of periodontitis development, such as pro-inflammatory reactions and microcirculation disorders, changes in the microbial biofilm. Pathophysiological changes in bone tissue in patients with T1D, which are associated with insulin deficiency and its anabolic effect on bone tissue, worsen the biomechanical and adaptive properties of bones and may contribute to the severity of periodontitis. The conducted analysis indicates the importance of further research to assess the oral health in children with T1D.

Correlation of diaphragmatic mobility and thickening assessed by lung ultrasound with severity of interstitial lung disease.

Studies conducted in interstitial lung disease (ILD) patients to assess diaphragmatic excursion and thickening fraction suggest a weak to strong correlation with pulmonary function parameters. However, diaphragmatic excursion velocity, a novel imaging marker, has not been correlated with pulmonary function and high-resolution computed tomography (HRCT) fibrosis score in ILD patients previously. We conducted a cross-sectional analytical study in 40 ILD patients during quiet (QB) and deep breathing (DB) to measure diaphragmatic thickening, excursion and excursion velocity using transthoracic ultrasound and correlated them with pulmonary function parameters and HRCT fibrosis score. Most diaphragm parameters in DB correlated more strongly with lung function parameters compared to quiet breathing. Right diaphragmatic excursion, during QB and DB, showed positive correlations with forced vital capacity (FVC) z-score (r = 0.591, 0.676) and diffusion capacity of the lung for carbon monoxide (DLCO) z-score (r = 0.437, 0.438), and negative correlations with HRCT fibrosis score (r = -0.439, -0.425), respectively. In addition, right diaphragmatic velocity exhibited positive correlations with FVC z-score (r = 0.388, 0.667) and DLCOz-score (r = 0.139, 0.412), and negative correlations with HRCT fibrosis score (r = -0.454, -0.445). Right diaphragm thickening fraction showed positive correlations with FVC z-score (r = 0.330, 0.460) and DLCOz-score (r = 0.400, 0.426), and negative correlations with HRCT fibrosis score (r = -0.199, -0.237). Similarly, right diaphragmatic thickness indicated positive correlations with FVC z-score (r = 0.526, 0.614) and DLCOz-score (r = 0.298, 0.298), and negative correlations with HRCT fibrosis score (r = -0.398, -0.401). Diaphragmatic excursion velocity during DB showed a weak to moderate correlation with pulmonary function parameters and HRCT fibrosis score and may be utilized as a surrogate marker in ILD patients unable to perform pulmonary function tests or undergo sequential HRCT thorax in follow-up.

Inflammatory bowel disease genomics, transcriptomics, proteomics and metagenomics meet artificial intelligence.

Various extrinsic and intrinsic factors such as drug exposures, antibiotic treatments, smoking, lifestyle, genetics, immune responses, and the gut microbiome characterize ulcerative colitis and Crohn's disease, collectively called inflammatory bowel disease (IBD). All these factors contribute to the complexity and heterogeneity of the disease etiology and pathogenesis leading to major challenges for the scientific community in improving management, medical treatments, genetic risk, and exposome impact. Understanding the interaction(s) among these factors and their effects on the immune system in IBD patients has prompted advances in multi-omics research, the development of new tools as part of system biology, and more recently, artificial intelligence (AI) approaches. These innovative approaches, supported by the availability of big data and large volumes of digital medical datasets, hold promise in better understanding the natural histories, predictors of disease development, severity, complications and treatment outcomes in complex diseases, providing decision support to doctors, and promising to bring us closer to the realization of the "precision medicine" paradigm. This review aims to provide an overview of current IBD omics based on both individual (genomics, transcriptomics, proteomics, metagenomics) and multi-omics levels, highlighting how AI can facilitate the integration of heterogeneous data to summarize our current understanding of the disease and to identify current gaps in knowledge to inform upcoming research in this field.

Deep estimation of the intensity and timing of natural selection from ancient genomes.

Leveraging past allele frequencies has proven to be key for identifying the impact of natural selection across time. However, this approach suffers from imprecise estimations of the intensity (s) and timing (T) of selection, particularly when ancient samples are scarce in specific epochs. Here, we aimed to bypass the computation of allele frequencies across arbitrarily defined past epochs and refine the estimations of selection parameters by implementing convolutional neural networks (CNNs) algorithms that directly use ancient genotypes sampled across time. Using computer simulations, we first show that genotype-based CNNs consistently outperform an approximate Bayesian computation (ABC) approach based on past allele frequency trajectories, regardless of the selection model assumed and the number of available ancient genotypes. When applying this method to empirical data from modern and ancient Europeans, we replicated the reported increased number of selection events in post-Neolithic Europe, independently of the continental subregion studied. Furthermore, we substantially refined the ABC-based estimations of s and T for a set of positively and negatively selected variants, including iconic cases of positive selection and experimentally validated disease-risk variants. Our CNN predictions support a history of recent positive and negative selection targeting variants associated with host defence against pathogens, aligning with previous work that highlights the significant impact of infectious diseases, such as tuberculosis, in Europe. These findings collectively demonstrate that detecting the footprints of natural selection on ancient genomes is crucial for unravelling the history of severe human diseases.

Association of Oral Microbiome with Periodontal Disease Progression: A Longitudinal Study

Periodontal disease, a prevalent oral health condition, is characterized by the inflammation and destruction of the supporting tissues around the teeth and poses significant challenges to global public health. Objectives: To examine the association between the oral microbiome and periodontal disease progression in a Pakistani population. Methods: A total of 350 patients aged ≥ 18 years, diagnosed with periodontal disease, were registered from August 2023 to February 2024. Participants were evaluated for periodontal health indicators, including probing depth and clinical attachment loss, and their oral microbiome profiles were analyzed using high-throughput sequencing of the 16S rRNA gene. Machine learning algorithms, including Random Forest and Support Vector Machines, were applied to predict disease progression based on microbial profiles. Results: Porphyromonas gingivalis and Tannerella forsythia were strongly associated with greater probing depths and clinical attachment loss (β = 0.45, p < 0.01), indicating their role in disease progression. Conversely, Streptococcus and Lactobacillus were linked to reduced disease severity (β = -0.30, p < 0.05). The oral microbiome exhibited high diversity, with Firmicutes (35%), Bacteroidetes (25%), Proteobacteria (20%), and Actinobacteria (15%) being the predominant species. The Random Forest model predicted disease progression with 85% accuracy (Area under the curve (AUC) = 0.87), emphasizing the predictive value of microbial profiles. Conclusions: It was concluded that the study confirms a strong link between specific oral microbiota and periodontal disease progression, emphasizing the importance of microbial analysis in predicting and managing periodontal health.

Disease severity and activity in bronchiectasis: A paradigm shift in bronchiectasis management.

Bronchiectasis has an increasing prevalence and substantial clinical and economic burden. Therefore, physicians should identify patients with bronchiectasis at high risk of disease progression to ensure optimal management in advance. The heterogeneity of bronchiectasis means it is unlikely that any single parameter could identify high-risk patients, therefore disease severity is usually assessed using validated composite tools, such as the Bronchiectasis Severity Index, FACED, and Bronchiectasis Aetiology Comorbidity Index, to predict long-term outcomes in bronchiectasis. Disease severity, however, implies an advanced process with lung destruction. Earlier intervention may prevent disease progression and improve outcomes. To identify patients at risk, rather than patients with established advanced disease, we need to shift our focus from disease severity to disease activity. Disease activity denotes the activation level of underlying pathophysiological processes and can be measured using clinical presentations and biomarkers. This review discusses a paradigm shift in bronchiectasis management, focusing on disease activity rather than severity, to prevent disease progression.

Alterations of gut microbiome in eosinophilic chronic rhinosinusitis.

A growing body of evidence has elucidated that the gut microbiota has a crucial impact on the pathophysiological process of atopic diseases. Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is a local atopic disease of the systemic immune response. Alterations in the gut microbiome in eCRSwNP patients remain largely undefined. 16S rRNA gene sequencing was performed in a cross-sectional study of 17 eCRSwNP patients, 9 noneCRSwNP patients and 13 healthy controls, and gut microbiota DNA sequencing between each pair of groups was compared using bioinformatic methods. Compared with that of healthy controls, the gut microbiomes of eCRSwNP patients were characterised by a distinct overall microbial composition. However, no significant differences were found in the alpha diversity of the gut microbiota between patients and healthy controls. The distinct differences in microbial composition were significantly correlated with the severity of disease. At the genus level, the abundance of Faecalibacterium positively correlated with Lund-Mackay CT scores. Similarly, the abundance of Turicibacter positively correlated with the percentage of tissue eosinophils. We found alterations in the gut microbiome in eCRSwNP patients, and the alterations in the gut microbiome were correlated with the severity of disease.

Sex-related differences in severe native valvular heart disease: the ESC-EORP Valvular Heart Disease II survey.

To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P < .001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months.

Harnessing nature's defenders: unveiling the potential of microbial consortia for plant defense induction against Alternaria blight in cumin.

Present study was aimed to develop an efficient microbial consortium for combating Alternaria blight disease in cumin. The research involved isolating biocontrol agents against Alternaria burnsii, characterizing their biocontrol and growth promotion traits, and assessing compatibility. A pot experiment was conducted during rabi season of 2022-2023 to evaluate the bioefficacy of four biocontrol agents (1F, 16B, 31B, and 223B) individually and in consortium, focusing on disease severity, plant growth promotion, and defense responses in cumin challenged with A. burnsii. Microbial isolates 1F, 16B, 31B, and 223B significantly inhibited A. burnsii growth in dual plate assays (~ 86%), displaying promising biocontrol and plant growth promotion activities. They were identified as Trichoderma afroharzianum 1F, Aneurinibacillus aneurinilyticus 16B, Pseudomonas lalkuanensis 31B, and Bacillus licheniformis 223B, respectively. The excellent compatibility was observed among all selected biocontrol agents. Cumin plants treated with consortia of 1F + 16B + 31B + 223B showed least percent disease index (32.47%) and highest percent disease control (64.87%). Consortia of biocontrol agents significantly enhanced production of secondary metabolites (total phenol, flavonoids, antioxidant, and tannin) and activation of antioxidant-defense enzymes (POX, PPOX, CAT, SOD, PAL, and TAL) compared to individual biocontrol treatment and infected control. Moreover, consortium treatments effectively reduced electrolyte leakage over the individual biocontrol agent and infected control treatment. The four-microbe consortium significantly enhanced chlorophyll (154%), carotenoid content (88%), plant height (78.77%), dry weight (72.81%), and seed yield (104%) compared to infected control. Based on these findings, this environmentally friendly four-microbe consortium may be recommended for managing Alternaria blight in cumin.

SARS-CoV-2 JN.1 variant: a short review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded, positive-sense RNA virus. The SARS-CoV-2 virus is evolving continuously, and many variants have been detected over the last few years. SARS-CoV-2, as an RNA virus, is more prone to mutating. The continuous evolution of the SARS-CoV-2 virus is due to genetic mutation and recombination during the genomic replication process. Recombination is a naturally occurring phenomenon in which two distinct viral lineages simultaneously infect the same cellular entity in an individual. The evolution rate depends on the rate of mutation. The rate of mutation is variable among the RNA viruses, with the SARS-CoV-2 virus exhibiting a lower rate of mutation than other RNA viruses. The novel 3'-to-5' exoribonuclease proofreading machinery is responsible for a lower rate of mutation. Infection due to the SARS-CoV-2, influenza, and respiratory syncytial virus has been reported from around the world during the same period of fall and winter, resulting in a "tripledemic." The JN.1 variant, which evolved from the predecessor, the omicron variant BA.2.86, is currently the most dominant globally. The impact of the JN.1 variant on transmissibility, disease severity, immune evasion, and diagnostic and therapeutic escape will be discussed.

Preserved prenatal lung growth assessed by fetal MRI in the omicron-dominated phase of the SARS-CoV-2 pandemic.

With SARS-CoV-2 evolving, disease severity and presentation have changed due to changes in mechanisms of entry and effector site as well as due to effects of vaccination- and/or infection-acquired immunity. We re-assessed fetal lung pathology in pregnancies with uncomplicated SARS-CoV-2 infections during the late, omicron-dominated pandemic phase to inform disease understanding and pregnancy consultation. In this case-control study, fetal lung volumes were assessed by fetal MRI in 24 pregnancies affected by mild maternal SARS-CoV-2 infection during the omicron-dominated pandemic phase with prevailing immunity through vaccination and/or prior SARS-CoV-2 infection. Fetal lung volumes (normalized to estimated fetal weight) in 24 pregnancies (GA 33.3 ± 3.8, 12 female fetuses) following mild, uncomplicated SARS-CoV-2 infection did not differ significantly from both, published reference values (96.3% ± 22.5% of 50th percentile reference values, p = 0.43), or fetal lung volumes of a site-specific, non-COVID control group (n = 15, 94.2% ± 18.5%, p = 0.76). Placental assessment revealed no group differences in thrombotic changes or placental heterogeneity (p > 0.05, respectively), and fetal lung volume did not correlate with placental heterogeneity when adjusting for gestational age at scan (p > 0.05). Assessment of fetal lung volume by MRI revealed unaffected lung growth in pregnancies affected by uncomplicated SARS-CoV-2 infection in the omicron-dominated pandemic phase in the presence of prevailing hybrid immunity. This finding contrasts sharply with the observed reduction in fetal lung volume following maternal alpha-variant infection in the pre-vaccination era and might reflect tropism- as well as immunity-related effects. Question: Is fetal lung development affected by mild maternal SARS-CoV-2 infection during the omicron-dominated phase of the pandemic? Fetal lung volume in 24 affected pregnancies did not differ significantly from published reference values or fetal lung volumes in 15 site-specific, non-COVID-affected control pregnancies. Preserved fetal lung volume following mild maternal SARS-CoV-2 infection during the omicron-dominated phase contrasts with previous findings of reduced volume in unvaccinated pregnancies during the alpha-dominated pandemic phase. These observations might reflect tropism- as well as immunity-related effects.

Utility of plasma nucleocapsid protein in predicting severity and prognosis in severe COVID-19 patients with comorbidities

ObjectivesThe COVID-19 pandemic poses ongoing challenges to global public health systems, emphasizing the critical necessity for efficient diagnostic and prognostic markers. This study evaluates the MAGLUMI® SARS-CoV-2 Ag N protein chemiluminescent immunoassay (MAG-CLIA) for its analytical performance and its role in predicting disease severity and prognosis among severe COVID-19 patients with comorbidities. MethodsAnalytical validation of plasma MAG-CLIA SARS-CoV-2 Ag N protein encompassed precision, interference, LoQ and linearity. Plasma N protein concentrations and other biomarkers were measured within 48 h of admission, tracked until discharge or death. The Mann-Whitney U test explored the association between plasma N protein and COVID-19 severity or prognosis. Longitudinal monitoring of plasma N protein dynamics was conducted in representative patients. ResultsMAG-CLIA demonstrated precise quantification of plasma N protein with a CV below 10 % and minimal interference. The LoQ was 0.88 ng/L, with a broad linear range. Plasma N protein showed high diagnostic accuracy for COVID-19, achieving 95.42 % specificity and 78.32 % sensitivity at 2.388 ng/L. Plasma N protein emerged as a valuable prognostic indicator, correlating with mechanical ventilation need and patient survival. Plasma N protein concentrations ≥ 424.3 ng/L (AUC 0.8102, sensitivity 78.38 %, specificity 85.48 %) were associated with poor prognosis in severe COVID-19 patients with comorbidities. ConclusionsMAG-CLIA’s SARS-CoV-2 N protein detection in plasma demonstrates both analytical reliability and clinical relevance in our inaugural evaluation. As a promising prognostic biomarker for severe COVID-19 patients, it offers crucial insights into disease severity and progression, emphasizing the significance of early monitoring and intervention, especially for patients with comorbidities.

Cost burden for healthcare and patients related to the unawareness towards laryngopharyngeal reflux.

To investigate the impact of physician unawareness towards laryngopharyngeal reflux (LPR) on healthcare costs. Patients with a confirmed LPR diagnosis were consecutively recruited from Belgian Hospitals. Demographics and clinical outcomes (impedance-pH testing features, reflux symptom score, and reflux sign assessment) were extracted. The past consultations and additional examinations dedicated to the investigation of laryngopharyngeal symptoms and findings without suspicion of LPR were collected. The estimated costs of consultations and procedures were those indicated in the National Health Insurance Institute's Charges for 2022. Part was reimbursed by the social security system, and the rest was paid by patients. Seventy-six patients were recruited. Seventeen patients (22.4%) had no previous consultation or additional examination for their LPR-symptoms. The estimated mean (standard deviation) costs related to the unawareness of LPR for the healthcare system and patient, were 310.06 ± 370.49 €, and 54.05 ± 46.28 €, respectively. The highest estimated costs were related to gastroenterology consultations and procedures, which did not lead to a confirmation of LPR diagnosis. The total estimated cost for the Belgian healthcare system and patients (11,590,000 million), could range from 359 359 540 € to 1 078 078 620 €; and 62 643 950 € to 187 931 850 €, respectively. The estimated costs related to gastroenterology practice of patients with severe disease were significantly higher than patients with mild disease. The unawareness of practitioners toward LPR leads to significant costs for healthcare system and patients. The teaching and awareness towards LPR need to be improved in medical schools and clinical practice.

Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial.

In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. Participants were randomised to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI) ornon-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorised by eGFR < or ≥60 mL/min/1.73 m2, UACR < or ≥300 mg/g or KDIGO risk classification. 3533 participants were randomised with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.9%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% (HR 0.82 [95% CI 0.68-0.98]; P = .03), with consistency across eGFR categories, UACR levels and KDIGO risk classification (all P-interaction >.13). Death due to any cause was reduced by 20% (HR 0.80 [0.67-0.95]; P = .01), with consistency across eGFR categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by UACR was .01 (<300 mg/g HR 1.17 [0.83-1.65]; ≥300 mg/g HR 0.70 [0.57-0.85]). Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with T2D.