Increased Disease Severity Research Articles

Validation of salivary proteomic biomarkers for early detection of oral cancer in the Egyptian population.

The present study evaluated the sensitivity and specificity of important proteomic salivary biomarkers; IL-6, IL-8, and sCD44 in the early detection of oral cancer, and any possible associations with risk factors of oral cancer in an Egyptian population. The present investigation was conducted on 100 individuals; 25 healthy controls, 25 patients having oral potentially malignant disorders (OPMDs) with dysplasia; 25 patients having OPMDs without dysplasia, and 25 oral cancer patients. Demographic data modified gingival index, oral hygiene level, and salivary levels of the biomarkers were assessed. Salivary levels of IL-6, IL-8, and sCD44 progressively increased with increased disease severity. Salivary IL-8 and IL-6 levels possess a discriminating potential from normal tissue through different degrees of dysplasia to oral cancer, sCD44 levels had a discriminating power between normal and dysplastic tissues with high sensitivity and specificity. A positive correlation was found between the three biomarkers and the grade of oral squamous cell carcinoma (OSCC) and with different risk factors. This is the first study that evaluated multiple salivary proteomic biomarkers in the Egyptian population, and the results validate the ability of IL-6, IL-8, and sCD44 to be used as sensitive diagnostic and prognostic biomarkers for screening and early detection of oral cancer.

Low Penetrance Sarcomere Variants Contribute to Additive Risk in Hypertrophic Cardiomyopathy.

Classically, hypertrophic cardiomyopathy (HCM) has been viewed as a single-gene (monogenic) disease caused by pathogenic variants in sarcomere genes. Pathogenic sarcomere variants are individually rare and convey high risk for developing HCM (highly penetrant). Recently, important polygenic contributions have also been characterized. Low penetrance sarcomere variants (LowSVs) at intermediate frequencies and effect sizes have not been systematically investigated. We hypothesize that LowSVs may be common in HCM with substantial influence on disease risk and severity. Among all sarcomere variants observed in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), we identified putative LowSVs defined by (1) population frequency greater than expected for highly penetrant (monogenic) HCM (allele frequency >5×10-5 in the Genome Aggregation Database, gnomAD) and (2) moderate enrichment (>2×) in patients with HCM compared with gnomAD. LowSVs were examined for their association with disease severity and clinical outcomes. Functional effects of selected LowSVs were assessed using induced pluripotent stem cell-derived cardiomyocytes. Association of LowSVs with HCM-adjacent traits in the general population was tested using UK Biobank cardiac magnetic resonance imaging data. Among 6045 patients and 1159 unique variants in sarcomere genes, 12 LowSVs were identified. LowSVs were collectively common in the general population (1:350) and moderately enriched in HCM (aggregate odds ratio, 14.9 [95% CI, 12.5-17.9]). Isolated LowSVs were associated with an older age of HCM diagnosis and fewer adverse events. However, LowSVs in combination with a pathogenic sarcomere variant conferred higher morbidity (eg, composite adverse event hazard ratio, 5.4 [95% CI, 3.0-9.8] versus single pathogenic sarcomere variant, 2.0 [95% CI, 1.8-2.2]; P<0.001). An intermediate functional impact was validated for 2 specific LowSVs-MYBPC3 c.442G>A (partial splice gain) and TNNT2 c.832C>T (intermediate effect on contractile mechanics). Cardiac magnetic resonance imaging analysis of the general population revealed 5 of 12 LowSVs were significantly associated with HCM-adjacent traits without overt HCM. This study establishes a new class of low penetrance sarcomere variants that are relatively common in the population. When penetrant, isolated LowSVs cause mild HCM. In combination with pathogenic sarcomere variants, LowSVs markedly increase disease severity, supporting a clinically significant additive effect. Last, LowSVs also contribute to age-related remodeling even in the absence of overt HCM.

Invertebrate herbivores influence seagrass wasting disease dynamics.

Although invertebrate herbivores commonly impact terrestrial plant diseases by facilitating transmission of plant pathogens and increasing host susceptibility to infection via wounding, less is known about the role of herbivores in marine plant disease dynamics. Importantly, transmission via herbivores may not be required in the ocean since saline ocean waters support pathogen survival and transmission. Through laboratory experiments with eelgrass (Zostera marina), we showed that isopods (Pentidotea wosnesenskii) and snails (Lacuna spp.) created grazing scars that increased disease severity and thus indirectly facilitated transmission of Labyrinthula zosterae (Lz), a protist that causes seagrass wasting disease. Experiments also quantified different feeding preferences among herbivores: Amphipods (Ampithoe lacertosa) selectively consumed diseased eelgrass, while isopods and snails selectively grazed asymptomatic leaves, suggesting different herbivore taxa may have contrasting impacts on disease dynamics. Our experiments show no sign that herbivores directly vector Lz from diseased to asymptomatic eelgrass. However, we isolated live Lz from isopod, amphipod, and snail feces and detected Lz with quantitative polymerase chain reactionin amphipods and snails, suggesting that herbivores eating diseased eelgrass could pass the live pathogen. Finally, field surveys demonstrated a close association between seagrass wasting disease and invertebrate grazing scars; disease prevalence was 29 ± 4.7% (95% CI) higher on eelgrass leaves with herbivore scars. Collectively, these findings show that some herbivores can increase eelgrass disease risk by facilitating the spread of an important pathogen via wounding, but not via direct transmission. Thus, herbivores may play different roles in plant disease dynamics in terrestrial versus marine ecosystems depending on the pathogen's ability to survive and transmit without a vector.

Prevalence and Incidence of Uveitis in Korean Patients with Sarcoidosis: A Population-Based Study

ABSTRACT Purpose Sarcoidosis is a systemic granulomatous inflammatory disease with varying clinical presentations, including sarcoid uveitis, which is the most prevalent ocular manifestation of sarcoidosis and differs by region and ethnicity. This study aims to determine the incidence and prevalence of sarcoidosis-related uveitis in South Korea, providing essential epidemiological data. Methods This nationwide, population-based retrospective study used the Korean Health Insurance Review and Assessment database from 2010 to 2019. It included all individuals diagnosed with sarcoidosis (ICD-10 code D86) and focused on those with newly developed uveitis. We assessed annual incidence, prevalence, gender-specific trends, age at diagnosis, treatment patterns, and recurrence. Cases were categorized as single episode or recurrent/chronic based on treatment duration and interval before recurrence. Results Among 9,485 patients with sarcoidosis, 2,730 (28.8%) had sarcoidosis-related uveitis, with 2,413 (88.4%) being recurrent/chronic. Anterior uveitis was the most common presentation (78.0%), with posterior segment involvement in 22.0% of cases. The peak age of onset was 50–59 years for both genders. The incidence rate was 0.33 and 0.64 per 100,000 for men and women, respectively. The prevalence was 0.18 and 0.35 per 100,000 for men and women, respectively. Among sarcoidosis patients, 32.9% with uveitis used three or more combinations of systemic steroids and immunosuppressants, compared to 11.1% without uveitis. Conclusion The high prevalence of sarcoid uveitis in sarcoidosis patients necessitates regular ophthalmic examinations. Our findings highlight the need for comprehensive eye care in managing sarcoidosis and suggest that uveitis may increase disease severity, warranting tailored treatment and enhanced monitoring protocols in Korea.

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Neutrophil swarming is crucial for limiting oral mucosal infection by Candida albicans.

Oral mucosal colonization by C. albicans (Ca) is benign in healthy people but progresses to deeper infection known as oropharyngeal candidiasis (OPC) that may become disseminated when combined with immunosuppression. Cortisone use and neutropenia are risk factors for invasive mucosal fungal infections, however the mechanisms are poorly understood. Here we identify in vivo neutrophil functional complexes known as swarms that are crucial for preventing Ca epithelial invasion. Anti-Ly6G antibody treatment impaired swarm formation and increased fungal infection depth confirming the role of neutrophil swarms in limiting Ca invasion. Neutrophil swarm function could be disrupted by administration of resolvins, and required leukotriene B4 receptor 1 (BLT1) expression so that administration of a leukotriene synthesis inhibitor reduced neutrophil swarm size permitting Ca invasion beyond the basement membrane. Cortisone treatment similarly reduced neutrophil swarming behavior and BLT1 expression and delayed expression of epithelial cytokines and chemokines. Thus, swarm structures have an important function in preventing deep invasion by C. albicans within the oral mucosa and represent a mechanism for increased disease severity under immune deficient clinical settings.

Risk Factors of the Severity of COVID-19 Infection in Infants

Background: The global COVID-19 crisis has profoundly affected populations worldwide. While it is widely accepted that older individuals are at greater risk of severe illness, data indicate that in newborns and infants, the disease is generally not fatal. Objectives: This cross-sectional study aimed to examine the roles of laboratory tests and clinical symptoms in determining the severity of COVID-19 infection in infants younger than three months. Methods: This study included all infants less than three months old with positive PCR tests for COVID-19 admitted to the Children's Medical Center between October 2020 and March 2022. We analyzed the association between disease severity and clinical symptoms, as well as laboratory findings. Results: Sixty-four neonates and infants under three months of age with COVID-19 participated in the study. Our findings suggest that lower birth weight and gestational age are associated with increased disease severity. Infants with underlying medical conditions were found to have a higher risk of reaching stage IIb or greater severity. Among laboratory and clinical findings, only white blood cell (WBC) count and cough symptoms showed a significant correlation with disease severity. Conclusions: Clinical evaluations, along with factors such as birth weight, gestational age, and underlying conditions, appear more effective in guiding decision-making for COVID-19 severity in infants. Further studies are necessary to explore the influence of these factors on COVID-19 severity in this age group.

Prognostic Implications of Initial Radiological Findings of Pulmonary Fibrosis in Patients with Acute SARS-CoV-2 Infection: A Prospective Multicentric Study.

Pulmonary fibrosis detected during the acute phase of SARS-CoV-2 infection may significantly influence patient prognosis. This study aimed to evaluate the prognostic value of initial high-resolution computed tomography (HRCT) findings of pulmonary fibrosis in hospitalized COVID-19 patients and to examine how these findings relate to disease severity and clinical outcomes, with a particular focus on the development and validation of predictive scoring systems. In this multicentric prospective cohort study from January 2023 to January 2024, 120 adult patients with confirmed SARS-CoV-2 infection requiring hospitalization were enrolled from two Romanian university hospitals. Patients were categorized based on the presence (n = 60) or absence (n = 60) of pulmonary fibrosis signs on admission HRCT scans, identified by reticular opacities, traction bronchiectasis, honeycombing, and architectural distortion. Biochemical analyses, severity scores (SOFA, APACHE II, NEWS 2), and novel compound scores combining clinical and radiological data were assessed. Patients with HRCT evidence of pulmonary fibrosis had significantly higher severity scores and worse clinical outcomes. The HRCT score alone was a strong predictor of severe COVID-19 (area under the ROC curve [AUC] = 0.885), with a best cutoff value of 9.72, yielding 85.7% sensitivity and 79.8% specificity. Compound Score 1, integrating SOFA, APACHE II, and HRCT scores, demonstrated excellent predictive performance with an AUC of 0.947, sensitivity of 92.5%, and specificity of 88.9%. Compound Score 2, combining systemic inflammation markers (SIRI, SII) and NEWS 2, also showed a strong predictive capability (AUC = 0.913), with 89.2% sensitivity and 85.7% specificity at the optimal cutoff. Regression analysis revealed that Compound Score 1 had the highest hazard ratio for severe COVID-19 outcomes (HR = 4.89; 95% CI: 3.40-7.05), indicating its superior prognostic value over individual markers and traditional severity scores. Initial HRCT findings of pulmonary fibrosis are significantly associated with increased disease severity in hospitalized COVID-19 patients. The HRCT score is a valuable prognostic tool, and, when combined with clinical severity scores into Compound Score 1, it enhances the prediction of severe COVID-19 outcomes with high sensitivity and specificity. These compound scores facilitate the early identification of high-risk patients, guiding clinical decision-making and optimizing patient management to improve outcomes.

Age-Associated Alterations in the Metabolome of Human Vitreous in Bacterial Endophthalmitis.

Endophthalmitis is a severe inflammatory condition due to intraocular infections that often leads to irreversible blindness. This study aimed to understand the age-dependent metabolic alterations in the vitreous of patients with bacterial endophthalmitis. The study included the vitreous metabolome of patients with bacterial endophthalmitis (group 1, n = 15) and uninfected controls (group 2, n = 14), which were further stratified into three groups according to their age: young (0-30years), middle (31-60years), and elderly (>60years). Vitreous samples were subjected to untargeted metabolomic analysis using high-resolution mass spectrometry (HRMS)m and acquired mass spectrometry data were analyzed using MetaboAnalyst 6.0. The altered metabolites with log2FC of ≥2/≤2, P < 0.05, and variable importance in projection > 1 were considered significant. In a total of 109 endogenous metabolites identified, young and elderly patients with endophthalmitis showed 52 (elevated, 25; reduced, 27; P < 0.05) and 27 (elevated, 19; reduced, 8; P < 0.05) significantly altered metabolites, respectively, compared to their age-matched controls. Additionally, 27 metabolites were differentially expressed in young patients with endophthalmitis compared to the older group. The crucial metabolic pathways dysregulated in the older infected population were de novo purine synthesis and salvage, carnitine, polyamine (spermidine), lipids (prostaglandins), and amino acid (taurine, methionine, histidine) which could possibly be attributed to the increased disease severity and inflammation observed in a clinical setting. Despite the erratic metabolic changes observed in the younger group infected with endophthalmitis when compared to age-matched controls, dysregulation in the specific pathways such as purine, carnitine, arachidonic acid, and polyamine metabolism could possibly alter the immunological exacerbation observed in the older group.

What is the spectrum of kidney pathology associated with COVID-19?

Kidney involvement occurs in almost one third of patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with increased disease severity. This review aims to outline the spectrum of kidney pathology involved in COVID-19. Literature was reviewed systematically on the databases Medline OVID and Scopus in search of case reports, case series, cohort studies and autopsy studies of patients with COVID-19 who underwent kidney biopsies. Studies were published between August 2020 and November 2021. Fourteen studies consisting of 159 patients were included in this review. Acute tubular necrosis is the most common pathology followed by collapsing glomerulopathy, occurring in 40.1% and 28.9% of patients respectively. Of the 46 patients with collapsing glomerulopathy, 44 were of African descent with high-risk apolipoprotein L1 genotypes. Less common glomerular diseases include membranous nephropathy, secondary focal segmental glomerulosclerosis, minimal change disease and primary focal segmental glomerulosclerosis occurring in 5%, 4.4%, 3.1% and 2.5% of patients respectively. Glomerulonephritis occurred in a minority of patients. Direct viral infection has not been found as a definitive aetiology. Acute kidney injury occurs frequently in hospitalised COVID-19 patients and is associated with increased morbidity and mortality. The mechanisms underpinning acute kidney injury are multifactorial. Acute tubular necrosis is the most common. Collapsing glomerulopathy is the most common glomerular injury and is strongly linked to apolipoprotein L1 genotypes. Improved understanding of COVID-19-related kidney pathologies can guide treatment to improve patient outcomes and reduce progression of chronic kidney disease. The longitudinal impact of COVID-19-related kidney disease requires further research.

PiSlope: A New CT Metric for Quantifying Airway Remodeling in Chronic Obstructive Pulmonary Disease.

Background Airway wall thickening is commonly quantified at chest CT with Pi10, the square root of the wall area of a hypothetical airway with a luminal perimeter of 10 mm. Although Pi10 has proven to be a useful construct, it assumes uniform thickening of all airways and considers only a single airway level in summarizing airway remodeling, limiting its accuracy. Purpose To evaluate PiSlope, a new metric for the quantification of airway wall thickening. Materials and Methods In this secondary analysis of data from a multicenter prospective study of individuals who currently smoke or formerly smoked as well as healthy volunteers who never smoked enrolled from January 2008 to June 2011 and followed up longitudinally until September 2022, chest CT images were analyzed section by section to quantify the luminal perimeter and airway wall thickness for each visible airway. Linear regression was used to calculate the slope of the luminal perimeter against wall thickness to determine the PiSlope. PiSlope was normalized by the individual's height squared. Multivariable regression was used to test the associations between airway metrics and respiratory outcomes. Results The mean age of the 8199 participants was 59.5 years ± 9.1 (SD), with 53% male and 67% White participants. With increasing disease severity (ie, Global Initiative for Chronic Obstructive Lung Disease stages 0-4), Pi10 increased (4.26 mm ± 0.23, 4.29 mm ± 0.21, 4.43 mm ± 0.26, 4.51 mm ± 0.28, and 4.53 mm ± 0.27, respectively) and PiSlope decreased (0.38 ± 0.10, 0.38 ± 0.10, 0.35 ± 0.11, 0.33 ± 0.10, and 0.31 ± 0.10) (trend test; both P < .001). Multivariable analyses revealed that PiSlope was associated with dyspnea, respiratory quality of life, 6-minute walk distance, exacerbations, lung function decline, and all-cause mortality, with and without Pi10 being included in the model. Conclusion The new metric PiSlope quantifies airway wall remodeling and shows associations with respiratory symptoms, quality of life, exacerbations, lung function decline, and all-cause mortality. Clinical trial registration no. NCT00608764 © RSNA, 2024 See also the editorial by Lynch in this issue.

T Regulatory Cell Subsets Do Not Restore for One Year After Acute COVID-19.

COVID-19, caused by SARS-CoV-2, triggers a complex immune response, with T regulatory cells (Tregs) playing a crucial role in maintaining immune homeostasis and preventing excessive inflammation. The current study investigates the function of T regulatory cells during COVID-19 infection and the subsequent recovery period, emphasizing their impact on immune regulation and inflammation control. We conducted a comprehensive analysis of Treg subpopulations in peripheral blood samples from COVID-19 patients at different stages: acute infection, early convalescence, and long-term recovery. Flow cytometry was employed to quantify Tregs including "naïve", central memory (CM), effector memory (EM), and terminally differentiated CD45RA+ effector cells (TEMRA). Additionally, the functional state of the Tregs was assessed by the expression of purinergic signaling molecules (CD39, CD73). Cytokine profiles were assessed through multiplex analysis. Our findings indicate a significant decrease in the number of Tregs during the acute phase of COVID-19, which correlates with heightened inflammatory markers and increased disease severity. Specifically, we found a decrease in the relative numbers of "naïve" and an increase in EM Tregs, as well as a decrease in the absolute numbers of "naïve" and CM Tregs. During the early convalescent period, the absolute counts of all Treg populations tended to increase, accompanied by a reduction in pro-inflammatory cytokines. Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors. Finally, we observed the re-establishment of CD39 expression in all Treg subsets; however, there was no change in CD73 expression among Tregs. Understanding these immunological changes across different T regulatory subsets and adenosine signaling pathways offers important insights into the disease's pathogenesis and provides a broader view of immune system dynamics during recovery.

The role of antibody-dependent enhancement in dengue vaccination

Dengue is the most rapidly spreading vector-borne disease worldwide, with over half the global population at risk for an infection. Antibody-dependent enhancement (ADE) is associated with increased disease severity and may also be attributable to the deterioration of disease in vaccinated people. Two dengue vaccines are approved momentarily, with more in development. The increasing use of vaccines against dengue, combined with the development of more, makes a thorough understanding of the processes behind ADE more important than ever. Above that, due to the lack of treatment options, this method of prevention is of great importance. This review aims to explore the impact of ADE in dengue vaccinations, with the goal of enhancing potential vaccination strategies in the fight against dengue.

Quantifying the impact of disease severity changes on the burden of blindness: A global decomposition analysis.

Despite the significant impact of blindness on the affected individuals' quality of life, its burden has not been assessed according to temporal cause-specific changes in severity, impeding our ability to evaluate the impact of blindness on population health accurately. Therefore, we aimed to comprehensively quantify the changes in cause-specific blindness burden according to changes in disease severity for 18 causes of blindness. For this cross-sectional population-based study, we derived data on prevalence, disability-adjusted life-years (DALYs), and population size between 1990 and 2019 from the Global Burden of Disease 2019 study. Using the decomposition method, we attributed changes in total DALYs to population growth, population ageing, and changes in prevalence rate and disease severity between 1990 and each subsequent year globally, regionally, nationally, and by sex, cause, and sociodemographic index (SDI). The absolute and relative contributions to the variation in blindness-related DALYs between 1990 and each year from 1991 to 2019 then served as a measure of changes in disease severity. Changes in disease severity from 1990 to 2019 were associated with 15 165.11 DALYs in men and 20 639.32 DALYs in women. We observed disease severity increases in most countries/territories, with attributable DALY proportions ranging from -0.07% to 1.30% in men and from -0.06% to 1.73% in women. Notably, both attributable proportions and DALYs were greater in women than men. The largest increases in attributable DALYs were observed for cataracts, refraction disorders, and glaucoma globally; age-related macular degeneration in high-SDI countries; and trachoma and retinopathy of prematurity in lower-SDI countries. Growth in the burden of cause-specific blindness due to increased disease severity reflects the lag of healthy vision life behind increasing life expectancy, necessitating the implementation of preventive and long-term therapeutic measures focussed on improving visual outcomes.

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

CRP Levels and Vitamin D as Predictors of Asthma Control: A Data-Driven Approach

Background: Asthma is a chronic inflammatory disease of the airways characterized by episodic exacerbations and airflow obstruction. Elevated C-reactive protein (CRP) levels indicate systemic inflammation and are associated with increased disease severity in asthma. Additionally, vitamin D is thought to modulate immune responses and inflammation, potentially influencing asthma control. This study explores the relationships between CRP levels, vitamin D levels, and asthma control, as measured by the Asthma Control Test (ACT). Objectives: The primary objective of this study was to assess the correlation between CRP levels, vitamin D levels, and asthma control in adult patients with asthma. The study aimed to determine whether CRP and vitamin D could serve as predictive markers for asthma control. Methods: This single-center, prospective observational study enrolled 40 adult patients with confirmed asthma from the outpatient pulmonary clinic of ESIC Government Hospital, Guwahati, Assam, India. Asthma control was evaluated using the ACT, with scores categorized as well-controlled (ACT ≥ 20) or poorly controlled (ACT &lt; 20). Serum CRP and vitamin D levels were measured using the ELISA method. Pearson’s correlation coefficient and ANOVA were employed to analyze the relationships between these variables. Results: The study found a moderate negative correlation between CRP levels and ACT scores (r = -0.58), indicating that higher CRP levels were associated with poorer asthma control. Patients with CRP levels greater than 10 mg/dL had significantly lower mean ACT scores compared to those with lower CRP levels. In contrast, a strong positive correlation was observed between vitamin D levels and ACT scores (r = 0.879), with higher vitamin D levels associated with better asthma control. The ANOVA test revealed significant differences in ACT scores across different vitamin D and CRP categories (p &lt; 0.05). Conclusions: The study suggests that elevated CRP levels are indicative of poorer asthma control, while higher vitamin D levels are associated with better control of asthma. CRP and vitamin D levels may serve as valuable biomarkers for assessing asthma severity and guiding treatment strategies. However, the variability in response to vitamin D supplementation highlighted the need for personalized approaches to asthma management. Further research is required to confirm these findings and explore the underlying mechanisms.

Early-Life Respiratory Syncytial Virus (RSV) Infection Triggers Immunological Changes in Gut-Associated Lymphoid Tissues in a Sex-Dependent Manner in Adulthood.

Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer's patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases.

Post-COVID-19-pandemic changes and clinical characteristics of invasive group a streptococcal infections from 2015 to 2023.

Since winter 2022, invasive GAS (iGAS) infections have re-emerged in Europe, causing severe diseases in children and adults. We aimed to examine whether this reported post-pandemic increase was associated with an increased disease severity and/or a shift in clinical disease phenotypes. We performed detailed clinical phenotyping of patients hospitalized with iGAS infections at a 1410-bed tertiary German Medical Center from 01/2015 to 09/2023. One hundred seventy-eight patients were included: 50 children (28.1%) and 128 adults (71.9%). IGAS infections of Q1/2023 exceeded the pre-pandemic average by 551% (1200% for children). The mean age of affected patients shifted significantly post-pandemically (49.5 ± 26.5 to 32.4 ± 28.2years of age, p < 0.05), mainly due to the higher percentage of children affected with iGAS infections (15.2% pre-pandemic, 44.2% post-pandemic). CFR was significantly lower for children (2%) compared to adults (11.7%) (p < 0.05) and decreased from 13% to 6.5% post-pandemically (p = 0.148). Duration of antibiotic therapy (13.5 (10 to 21) to 10 (9 to 14) days), length of hospital (10 (4 to 25) to 7 (5 to 15) days), and ICU stay (7.0 (2.5 to 18.0) to 5.0 (3.0 to 8.5) days) were shorter post-pandemically. Despite the higher post-pandemic percentage of affected children, PICU admissions (57% before to 32% after), use of catecholamines (28.6% to 11.8%), invasive ventilation (35.7% to 17.6%) and CFR (7% to 0%) were all lower after the pandemic. Children were at higher risk for iGAS infections post-pandemically. The surge of post-pandemic iGAS infections was not accompanied by increased iGAS-associated morbidity and mortality.

Potential protective association of the AA genotype and a allele of CXCR4 rs2228014 polymorphism with COVID-19 severity in adult egyptians

BackgroundBy the end of December 2019, a new coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, and the cause of the disease was named coronavirus disease 2019 (COVID-19). Several genetic factors have been implicated in diverse responses to SARS-CoV-2 infection, such as the C-X-C chemokine receptor 4 (CXCR4) rs2228014 polymorphism, which has been previously studied in various diseases but has not been explored in the context of COVID-19 severity. The current study aimed to assess the association between the rs2228014 polymorphism in the CXCR4 gene and the severity of COVID-19, which has not been previously reported.MethodThis cross-sectional study analyzed 300 adult Egyptian COVID-19 patients (156 with mild or moderate and 144 with severe or critical symptoms) admitted to Assiut University Quarantine Hospital from June to September 2022 during the omicron variant. The rs2228014 polymorphism in the CXCR4 gene was detected using real-time PCR with a TaqMan assay probe. Receiver operating characteristic (ROC) curve analysis was used to determine the best cutoff values for C-reactive protein (CRP) that can be used to estimate the severity of COVID-19. P values less than 0.05 were considered to indicate statistical significance.ResultsNo significant differences in the allelic or genotypic frequencies of CXCR4 rs2228014 were detected between the severity groups. However, the exclusive presence of the AA genotype in mild or moderate cases suggests its potential protective role. Additionally, significant differences in myalgia presentation, leukocyte counts and antibiotic use, were observed among different genotypes. Statistical data showed that the severity of COVID-19 could be predicted at a cutoff value of CRP > 30 mg/L, with a sensitivity of 74.3% and a specificity of 42.9%.ConclusionThe present findings suggest a potential protective role of the AA genotype and A allele of CXCR4 rs2228014 against severe COVID-19. Additionally, factors such as lack of vaccination and comorbidities such as hypertension, renal disease, and diabetes mellitus were associated with increased disease severity.

The Triglyceride-Glucose Index as a Marker in Idiopathic Restless Legs Syndrome.

Background and objective Restless legs syndrome (RLS) is more common in diabetic patients than in the general population. In this study, we aimed to explore the association between idiopathic RLS and the triglyceride-glucose (TyG) index, which is a simple and accessible markerof insulin resistance (IR). Materials and methods The study included 200 patients diagnosed with RLS according to the International Restless Study Group criteria, as well as 112 healthy volunteers. We interpreted the variables related to TyG and RLS by using the Pearson correlation coefficient and independent samples t-test. Multivariate linear regression analyses and receiver operating characteristic (ROC) curve analyses were employed to demonstrate the discriminatory power of the variables. Results The mean age of the patients with RLS was 44.73 ±11.29 years, and 71.5% (n=43) were female. The level of triglycerides, as well as BMIand TyG index, were significantly higher in patients with RLS compared to the control group (p=0.040, p=0.001, p=0.019, respectively). The TyG index showed a positive correlation with both disease duration (months) and BMI (r=0.281, p=0.000; r=0.507, p=0.000). The results of the multivariate regression analysis indicated a linear relationship between the TyG index and increasing RLS severity and BMI (β=0.286, t=4.199, p=0.000; β=0.041, t=6.754, p=0.000). Conclusions Our study revealed a direct correlation between the TyG index and increased disease severity, disease duration, and BMI in RLS. The findings indicate that the TyG index may serve as a valuable marker for RLS severity and high BMI.