Disease Severity Research Articles

Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis.

In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI). Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity. Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy. These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.

Fractional CO2 Laser-Assisted Delivery of Botulinum Toxin-A Versus Aluminum Chloride in Treatment of Primary Palmar Hyperhidrosis.

Primary palmar hyperhidrosis (PPH) constitutes a distressing dermatologic condition that greatly affects patients' quality of life. Its management still needs to be addressed to find a suitable therapeutic modality that is readily available, cost effective, and gives patients a quite long disease-free period. To assess the efficacy of fractional CO2 laser as a delivery method for botulinum toxin-A (BTX-A) and aluminum chloride in treating PPH. Twenty-four subjects with PPH were treated on both hands with fractional CO2 laser followed on the right hand with topical BTX-A and on the left hand with topical aluminum chloride. Minor's starch-iodine test and Hyperhidrosis Disease Severity Scale (HDSS) were used for evaluation of treatment response and for follow-up. There was a significant improvement in HDSS in both groups, but there was no statistically significant difference in the therapeutic response for both modalities. There was a statistically significant longer disease-free period in the BTX-A-treated hands. Fractional CO2 laser-assisted drug delivery (LADD) represents a safe, minimally invasive procedure that enhances the delivery of BTX-A and aluminum chloride, the two most widely used agents for treating PPH, with a comparable anhidrotic response.

Genetic variations in Interferon-Induced with Helicase C Domain 1: Impact on COVID-19 risk and severity in the Moroccan population

BackgroundThe clinical spectrum of COVID-19 varies considerably, ranging from asymptomatic cases to severe disease and even death. This variability can partly be attributed to genetic differences in genes associated with inflammation and immune responses. Among these genes, Interferon Induced with Helicase C Domain 1 (IFIH1), which codes for a cytoplasmic sensor, plays a crucial role in detecting SARS-CoV-2 viral RNA and initiating the antiviral interferon (IFN) response, thereby constituting a key element of innate immune defense. AimThis study aims to examine the association between genetic variants in the IFIH1 gene and susceptibility to, as well as the severity of, COVID-19 in the Moroccan population. Materials and MethodsWe conducted a case-control study involving 299 COVID-19 positive patients (149 severe, 150 benign) and 145 uninfected-SARS-CoV-2 controls. We determined the genotypes of two functional variants, rs1990760 (Ala946Thr) and rs3747517 (His843Arg), in the IFIH1 gene using predesigned TaqMan real-time allelic discrimination assay. ResultsOur results indicated that the TT genotype of rs1990760 was associated with increased susceptibility to SARS-CoV-2 under a recessive model (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.28–3.84, P=0.003). Conversely, the CT genotype appeared to confer protection against SARS-CoV-2 infection (OR=0.58, 95 % CI 0.38–0.91, P=0.016) and COVID-19 severity (OR=0.56, 95 % CI 0.34–0.91, P=0.019). No significant association was found between rs3747517 and the risk of hospitalization or infection susceptibility. ConclusionThese findings underscore the significance of genetic variability in the IFIH1 gene in shaping individual responses to SARS-CoV-2 in the Moroccan population.

At-home wearable-based monitoring predicts clinical measures and biological biomarkers of disease severity in Friedreich’s Ataxia

BackgroundFriedreich ataxia (FRDA) results in progressive impairment in gait, upper extremity coordination, and speech. Currently, these symptoms are assessed through expert examination at clinical visits. Such in-clinic assessments are time-consuming, subjective, of limited sensitivity, and provide only a limited perspective of the daily disability of patients.MethodsIn this study, we recruited 39 FRDA patients and remotely monitored their physical activity and upper extremity function using a set of wearable sensors for 7 consecutive days. We compared the sensor-derived metrics of lower and upper extremity function as measured during activities of daily living with FRDA clinical measures (e.g., mFARS and FA-ADL) and biological biomarkers of disease severity (guanine-adenine-adenine (GAA) and frataxin (FXN) levels), using Spearman correlation analyses.ResultsThe results show significant correlations with moderate to high effect sizes between multiple sensor-derived metrics and the FRDA clinical and biological outcomes. In addition, we develop multiple machine learning-based models to predict disease severity in FRDA using demographic, biological, and sensor-derived metrics. When sensor-derived metrics are included, the model performance enhances 1.5-fold and 2-fold in terms of explained variance, R², for predicting FRDA clinical measures and biological biomarkers of disease severity, respectively.ConclusionsOur results establish the initial clinical validity of using wearable sensors in assessing disease severity and monitoring motor dysfunction in FRDA.

Combi-Elastography versus Transient Elastography for Assessing the Histological Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH. Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis. A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792). The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Novel TBC1D8B variant causes neonatal nephrotic syndrome combined with acute kidney injury

BackgroundNephrotic syndrome (NPHS), characterized by proteinuria, hypoalbuminemia, and edema, can be caused by genetic variations. TBC1D8B was recently discovered as a novel disease-causing gene for X-linked NPHS. With only a few reported cases, the clinical manifestations associated with variants of this gene need to be further examined.MethodsWe recruited a newborn with NPHS complicated by acute kidney injury (AKI) and his parents and tested the potential genetic cause of the disease through trio-whole exome sequencing and Sanger sequencing. Western blotting (WB) was performed using a mutant plasmid to evaluate mutant protein expression levels. Since the TBC1D8B protein interacts with RAB proteins to catalyze the GTPase hydrolysis process, immunofluorescence (IF) can be used to verify the interaction between the TBC1D8B mutant protein and RAB11A/RAB11B, and thus to confirm its effect on the endocytosis and vesicle recycling functions of RAB proteins within the cell.ResultsThe child, at 1 month, showed severe edema and proteinuria and unexplained coma with epilepsy. Ultrasound examination revealed multiple organ enlargement, and MRI showed nonspecific high diffusion-weighted imaging signal characteristics in the splenium of the corpus callosum. Hematoxylin and eosin staining showed diffuse inflammatory cell infiltration in the renal interstitium and multifocal renal tubule lumen expansion. Diffuse fusion of podocyte foot processes was observed under electron microscopy, indicating glomerular podocyte lesions. Genetic testing revealed a maternally inherited novel hemizygous variant, NM_017752: c.628 A > T, p.Lys210Ter, in TBC1D8B. In vitro functional experiments showed that this variant may lead to TBC1D8B protein degradation. IF results showed disrupted interaction with RAB11A/RAB11B, that then affects the biological function of RAB proteins in the process of cell intimal vesicle formation and intracellular transport.ConclusionThis study will enrich the mutational and phenotypic spectra of TBC1D8B and demonstrate the potential of this gene variants to cause early-onset NPHS leading to severe kidney disease.

Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD). In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial. Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II. FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

Protein phosphatase 1 suppresses PKR/EIF2α signaling during human cytomegalovirus infection.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects the majority of the world's population. Lytic HCMV replication in immunocompromised individuals or neonates can lead to severe disease in multiple organ systems and even death. The establishment of lytic replication is driven by the first viral proteins expressed upon infection, the immediate early proteins, which play a key role in creating an intracellular environment conducive to virus replication. Two immediate early proteins, the functional orthologs pTRS1 and pIRS1, stimulate immediate early gene expression by suppressing antiviral PKR/eIF2α signaling and enhance the translation of viral mRNAs independent of PKR antagonism. To better understand the molecular functions of pTRS1, we used proximity labeling proteomics to identify proteins that interact with pTRS1 in infected cells. Multiple novel host and viral interactors were identified, including the catalytic subunits of the protein phosphatase 1 (PP1) holoenzyme. Mutations to a PP1 catalytic subunit known to disrupt binding to PP1 regulatory subunits decreased binding to pTRS1. pTRS1 immune complexes contained phosphatase activity, and inhibition of phosphatase activity in transfected or infected cells reversed the ability of pTRS1 to inhibit the antiviral kinase PKR. Depletion of individual PP1 catalytic subunits decreased virus replication and increased the phosphorylation of the PKR substrate eIF2α. Taken together, our data suggest potential novel functions for pTRS1 and define a novel role for PP1 as an antagonist of the antiviral PKR/eIF2α signaling axis during HCMV infection.IMPORTANCEThe human cytomegalovirus (HCMV) pTRS1 and pIRS1 proteins are critical regulators of HCMV replication, both during primary infection and during reactivation from viral latency. Thus, defining the molecular functions of pTRS1/pIRS1 is important for understanding the molecular events controlling HCMV replication and viral disease. These data provide new insights into potential pTRS1 functional roles, providing a starting point for others to understand new features of infected cell biology. Another important result of this study is the finding that specific protein phosphatase 1 (PP1) regulatory subunits are required to suppress PKR/eIF2α signaling, a critical cellular innate immune defense to viral infection. These data lay the groundwork for future efforts to discover therapeutics that disrupt pTRS1 interaction with PP1 allowing cellular defenses to limit HCMV replication and disease.

The role of angiotensin II and endothelin receptor antibodies in COVID19 patients with HFpEF

Abstract Background The infection caused by the coronavirus SARS-COV-2, is associated with an unusual pattern of organ damage in comparison to other viral-induced pathologies. A theory of autoimmunity induced by ACE-2/SARS-COV-2 spike protein complex or its degradation products, was proposed as a possible explanation for the versatile and multiorgan damage in COVID-19. Aim The aim of the study is to determine whether antibodies against angiotensin II receptor type 1 (AT1R) or endothelin-1 receptor type A (ETAR) do exist in plasma of COVID -19 patients with heart failure with preserved ejection fraction and whether they correlate to the severity of the disease. Methods A total of 61 patients with COVID-19 and heart failure with preserved ejection fraction and 48 controls (free of COVID19) with heart failure with preserved ejection fraction were included. Patients were divided into two groups: patients with severe disease (admitted at the intensive care (n=30)), patients with milder clinical presentation that remained in the general therapeutical department (n=31). The plasma levels of IL-6 and auto-antibodies against AT1R or ETAR in peripheral blood were measured and compared between COVID19 patients with severe and milder disease and age matched controls. Clinical and standard laboratory parameters were also collected and their association with the research biomarkers was analysed. Results Auto-antibodies against AT1R were significantly increased in severe disease course (median 19.60 U/mL, IQR 4.8-34.75) compared to milder disease (median 10.95 U/mL, IQR 7.69 – 17.67, p=0.017) and the control group (median 6.79 U/mL, IQR 5.10 – 14.05, p&amp;lt; 0.001). ETAR antibody titers were also significantly increased in severe disease (median 14.52, IQR 6.76-32.94), compared to milder disease course (median 8.73 U/mL, IQR 6.59 –13.45, p=0.023) and to the control group (median 6.64, IQR 6.79 – 17.92, p &amp;lt;0.001). The same was the trend regarding IL-6 antibodies. Severe disease (median 12.11 U/mL, IQR 5.59–19.38); milder disease disease (median 8.64U/mL, IQR 1.84 – 14.13, p=0.039); control group (median 4.28U/mL, IQR 0.11–1.43, p&amp;lt;0.001).Both AT1R and ETAR correlated to IL-6 plasma levels. The results did not show association with the concomitant therapy. Conclusion In conclusion, we establishеd the presence of AT1R and ETAR autoantibodies in COVID-19 patients with heart failure with preserved ejection fraction. They correlated to IL-6 plasma levels (systemic inflammation) and are associated with severe form of the disease.

The association between mammographic breast density, epicardial adipose tissue volume and coronary artery disease

Abstract Background Dysfunctional adipose tissue is strongly linked to cardiometabolic disease. Epicardial adipose tissue (EAT) which is measurable on cardiac computed tomography (CT) is well correlated with cardiovascular disease (CVD), however it is not reported clinically. Breast mammography mandates reporting of breast density (BD), which is also a marker of breast adipose tissue quantity with less dense breasts indicating greater adipose tissue volume. Given the widespread use of screening mammography, this presents an opportunity to employ BD as a possible surrogate for CVD risk. Purpose To evaluate the correlation between BD, EAT and coronary artery disease (CAD). Methods Single-centre, retrospective, cross-sectional study, including women who had both clinically indicated coronary computed tomography angiogram (CCTA) and mammography. Epicardial adipose tissue volume (EATv) was quantified using semi-automated software (QFAT 2.0). BD was visually assessed by standard 4-level Breast Imaging-Reporting and Data System (BI-RADS) grade with grade A-B representing low density, and C-D representing high density. CAD was categorised as presence/absence of any coronary artery plaque, and CAD severity was quantified using the Coronary Artery Disease Reporting and Data Systems (CAD-RADS) score, with CAD-RADS 1-2 representing mild disease, CAD-RADS 3 moderate disease and CAD-RADS 4 severe disease. CAD analyses were adjusted for modifiable (hypertension, dyslipidaemia, diabetes, body mass index) and non-modifiable (age, past smoking, family history, breast cancer) risk factors. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Results Among 153 patients (mean age 62±10), 103 (67.3%) had low BD (high breast adiposity). Compared with high BD, low BD patients were older, had greater rates of hypertension, had significantly higher mean EAT (106.6 ± 43.0 vs 81.0 ± 31.6ml, p&amp;lt;0.001) (Figure 1), and body mass index (30.5 ± 6.3 vs 26.4 ± 5.4kg/m², p&amp;lt;0.001). Adjusted for age and hypertension, EATv remained independently predictive of low BD (OR:1.02 [1.01-1.03], p=0.006). Low BD made up a higher proportion of mild (76.5%), moderate (73.9%) and severe (80.0%) disease. Low BD was strongly associated with presence of CAD (prevalence 75% vs 48%, OR 3.21 [1.58-6.53], p=0.001) independent of EATv (p=0.25), and independent of modifiable (OR: 2.69 [1.24-5.92], p=0.012) and non-modifiable (OR: 2.42 [1.04-5.85], p=0.047) risk factors (Figure 2). Conclusions Low breast density is associated with higher EATv and independently associated with CAD presence beyond EATv and other risk factors. Consequently, mammographic breast density may act as an early risk identification tool for CAD in women.

Risk of long COVID in migrants and the contribution of vaccinations, disease severity, social inequalities and preexisting health: A nationwide register study in Sweden

Abstract Background and aim A number of studies have found higher COVID-19 infection rates, hospitalizations and deaths in migrants and ethnic minorities throughout the Corona Pandemic. Some recent evidence also suggests higher risk of long COVID in migrants although less is known about the risk factors for long COVID in this population. The objective of our study is to examine the risk of long COVID in migrants and to examine whether preexisting health conditions, disease severity, social inequalities and vaccinations contribute to the association. Methods We used linked Swedish administrative registers to estimate the risk of a long COVID diagnosis in the population that had a confirmed COVID-19 infection. Poisson regressions were used to calculate incidence rate ratios between the Swedish born and migrant groups. Adjustments for preexisting health conditions, disease severity, vaccinations and social inequalities were separately introduced. Results Higher risks of long COVID were found among migrants from Africa, Asia, Eastern Europe, Finland, Middle-East and South America. While the contribution of vaccinations and social inequalities were modest, we found that disease severity (i.e. whether the person was hospitalized or treated in an intensive care unit) primarily contributed to the higher risk of long COVID found in migrants. Conclusions The greater exposure and impact of the COVID-19 virus among migrants during the pandemic also affected the longer-term consequences of infection in this at-risk population.

Predicting the severity of valvular heart diseases using ai integrated with ECG and anthropometric data

Abstract Background AI has been used in studies to predict the severity of aortic stenosis (AS) from electrocardiography (ECG), but the application of AI to predict the severity of aortic regurgitation (AR), mitral regurgitation (MR) and tricuspid regurgitation (TR) has not been widely explored. This study aimed to determine whether deep learning can predict the severity of valvular heart disease (AS, AR, MR and TR) assessed by echocardiography using ECG data. Methods and Results We analyzed data from 31,787 adult patients who underwent ECG and echocardiography within three days of each other between 2014 and 2019 at two hospitals. Valvular heart diseases, including AS, AR, MR, and TR, were classified into categories; normal, mild, moderate, and severe; according to guidelines. ECGs, along with patient age, gender, height, and weight, were inputs to a LightGBM machine learning model. The model was trained on 80.6% of the data, with the remaining 19.4% used for validation. The sensitivity for predicting moderate or severe valvular heart disease was 85% for AS, 88% for AR, 85% for MR, and 85% for TR. The negative predictive values for AS, AR, MR, and TR were all 100%. Prediction accuracies for the severity of each disease were AS at 0.857, AR at 0.871, MR at 0.855, and TR at 0.890. Predictions based on AS diagnostic parameters; mean pressure gradient, valve area, and maximum blood flow velocity also showed favorable accuracies at 0.891, 0.821, and 0.877, respectively. Conclusion Integrating AI with standard clinical parameters, including ECG data, height, and weight, showed potential in accurately predicting the severity of various valvular heart diseases. Further researches across diverse populations and settings are necessary to validate the approach's effectiveness and explore its impact on patient care.

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p &amp;lt; 0.001), hs-Troponin T (β = 3.391, p &amp;lt; 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p &amp;lt; 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.

Iron status in children with acute COVID-19 and paediatric inflammatory multisystem syndrome during infection and after recovery

BackgroundCOVID-19 has significant effects on organ function, particularly on lung function and iron metabolism. Studies have shown increased levels of ferritin, an iron storage protein, in COVID-19 patients, indicating potential changes in iron utilization. Research has focused primarily on adults, with limited studies on paediatric patients and a lack of comparisons with MIS-C patients. This study aimed to assess iron status in paediatric COVID-19 patients using traditional and new biomarkers, soluble transferrin receptors (sTfR) and Reticulocyte hemoglobin equivalent (RET-He), to improve diagnosis and prognosis. Additionally, we sought to compare iron status between acute COVID-19 patients and MIS-C patients and evaluate the relationships among iron dysmetabolism, disease severity, and prognosis in paediatric patients. The study also involved monitoring iron status during and after infection to understand its impact on patient severity and prognosis.MethodsA cohort study involving 49 patients aged 1 month to 18 years was conducted at the isolation department of Mansoura University Children's Hospital. The study included 36 patients with acute COVID-19 and 13 with multisystem inflammatory syndrome of childhood (MIS-C). Diagnosis was based on PCR from a deep nasopharyngeal swab or a positive antibody test. Follow-up of survivors was conducted 3 months after recovery. Blood samples were obtained during infection and at follow-up for CBC, Ret-He, iron kinetics, and sTfR analyses.ResultsSignificant iron deficiency anaemia was observed in all patients during infection, with improvement after 3 months of recovery in survivors. The improvement was more obvious in MIS-C patients, with Hb and iron kinetics not significantly affected by disease severity. The STfR was significantly lower in nonsurvivors than in survivors. The ROC curve showed that a baseline sTfR ≤ 18 nmol/L was a statistically significant difference between nonsurvivors and survivors (area under the curve (AUC) = 0.810, p < .001), with 66.7% sensitivity and 82.5% specificity. Regression analysis revealed that patients with baseline sTfRs ≤ 18 nmol/L were 5.9 times more susceptible to death.ConclusionThis study revealed that COVID-19 in children caused iron deficiency anaemia, which improved within 3 months after recovery. Haemoglobin and sTfRs were identified as reliable indicators of IDA in these patients, unlike iron kinetics and RET-He.

Quality of life measures with etripamil self-administration for acute episodes of paroxysmal supraventricular tachycardia in a medically unsupervised setting: patient-reported outcomes from NODE-303

Abstract Background Etripamil nasal spray (NS) is a fast-acting, self-administered calcium-channel blocker in development for the conversion of AV-nodal dependent paroxysmal supraventricular tachycardia (PSVT) in a medically unsupervised setting. Prior studies show favorable safety and efficacy in converting single episodes of PSVT to sinus rhythm (SR). Purpose In NODE-303, patient-reported outcome (PRO) instruments assessed quality of life (QoL) over multiple etripamil-treated episodes of PSVT. Methods NODE-303 was an event-driven, multi-center, open-label Phase 3 study in North and South American patients with documented PSVT that evaluated the safety and efficacy of etripamil in PSVT termination, over multiple episodes and without the need for prior test dosing. Enrolled patients who perceived PSVT symptoms applied an ambulatory ECG cardiac monitoring system (CMS), performed a pre-trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. A study amendment allowed a repeat dose (etripamil NS, 70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes. Safety was assessed through adverse events, clinical data, and ECG CMS recordings. The Treatment Satisfaction Questionnaire for Medication (TSQM; validated for acute episodic assessments) and other PROs were administered, and healthcare utilization data were acquired. Patients completed PROs at baseline (BL), monthly, and per PSVT episode, which collected information on symptoms, episode characteristics, rescue medications, and emergency room visits. Additional PROs were the Brief Illness Perception Questionnaire (BIPQ), Cardiac Anxiety Questionnaire (CAQ), and 36-Item Short Form Health Survey (SF-36). Results There were higher proportions of patients reporting mild, minimal or no disease severity, every 6 months, than at BL; extremely severe, severe, and moderate disease severity was reported by smaller proportions of patients than at BL, though incomplete surveys at later visits may limit this analysis. Anxiety and stress about future PSVT episodes were consistently reduced from BL. Measures of treatment satisfaction, effectiveness, and convenience were consistent across multiple episodes, and were at levels considered favorable for the TSQM instrument (Table 1). Rates of emergency-room visits and hospital admissions across multiple, treated PSVT episodes were similar to those observed in trials assessing single episodes (Table 2). The BIPQ, CAQ or SF-36 had no notable changes from BL. Conclusions Etripamil self-administration was associated with patient-reported improvements in degree of disease severity, decreased anxiety and stress over future PSVT episodes, and levels of treatment satisfaction, effectiveness, and convenience considered favorable for respective PRO instrument. Using a symptom-prompted, self-administered treatment for PSVT could potentially improve QoL measures and reduce healthcare resource utilization.

Developing survey instruments for low back and neck pain to improve disease severity estimates for burden of disease assessment

Abstract Two people living with the same disease can have very different experiences; one has little consequence, whilst the other struggles with much more debilitating consequences that impacts how they live their lives day-to-day. A growing body of research highlights the need for better estimates of disease severity to facilitate better estimation of the non-fatal burden of disease (BOD). Routine data does not always offer solutions because it’s often not coded at a granular enough level to map to individual health states. Data offering solutions are scarce and therefore not available across time or space. Most commentators have quantified the problem of assuming the same proportional severity splits to fill data gaps; a problem common to the Global Burden of Disease (GBD) study and independent BOD studies. However, whilst the need for highlighting the problems associated with this assumption remains, there are other positive steps that can be taken to overcome it. We propose how reproducible approaches can be developed, and present how they can be used to develop disease severity estimates. This involves developing a survey instrument to estimate the overall and health state prevalence of back pain and neck pain, basing health state definitions from the GBD non-fatal disease models, where the classification of cases by severity is based on the combination of respondent’s answers. Furthermore, we discuss how self-assessed severity estimates allow for internal validity checks, but also more widely offer opportunities to appraise the appropriateness of GBD non-fatal disease models. The development, and publication, of survey instruments can assist both independent studies and the GBD study to improve estimates of disease severity, as well as retaining important opportunities for cross-country comparability. Understanding the spectrum of severity is important for understanding how disease impacts populations and can inform healthcare provision and expenditure strategies.

A recent shift in the Puccinia striiformis f. sp. tritici population in Serbia coincides with changes in yield losses of commercial winter wheat varieties

Wheat yellow (stripe) rust, caused by the fungus Puccinia striiformis f.sp. tritici (Pst), is a devastating disease of wheat worldwide. The success of Pst is largely due to the pathogens ability to rapidly overcome host resistance, generating new races that are easily dispersed between territories through wind-borne transmission of Pst urediniospores. Thus, first signs of entry of new Pst races into a region is usually captured by changes in disease severity. To examine any alterations of winter wheat variety response to Pst infection in Serbia, we analyzed yield and Pst disease severity in field trials conducted in 2014, 2021, and 2023. We specifically focused on analyzing Pst disease severity at growth stages related to yield. Associations between qualitative variables (variety, year) and quantitative variables (yield in untreated plots, yield loss, and disease index (DI) of Pst infection) were analyzed using Principal Component Analysis with mixed data. A General Linear Model was used to investigate the most influential factors on yield, yield loss, and Pst infection. The results indicated that yellow rust disease severity increased over the past decade, suggesting a potential recent change in the Pst population in Serbia. Comparative population genetic analysis of Pst samples from the 2023 wheat season and those collected in Serbia in 2014 confirmed a potential change in the Pst population. In addition, we found that yield losses across wheat varieties varied independently of Pst infection levels, indicating that wheat varieties differ in their ability to overcome damage caused by high levels of Pst infection. Given that the level of pathogen pressure triggering susceptibility reactions is cultivar-specific, our study highlights the need for a deeper focus on the mechanisms underlying these differences. Expanding our understanding of the interactions between pathogens, plant defense responses, and the ability of cultivars to mitigate yield losses will better equip us to predict and prevent potential yield losses in commercial wheat varieties due to yellow rust in the future.

Patients vaccinated against COVID-19 present better coronary flow, myocardial work and NTproNP levels than non-vaccinated at 4 months post COVID infection

Abstract Introduction COVID-19 affected patients present impaired subclinical markers of cardiovascular and endothelial function post resolution of infection. Whether vaccination impedes impairment of myocardial and vascular function has not been clarified. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function in vaccinated and non-vaccinated subjects at four months after the infection. Methods We recruited 60 vaccinated and 60 non-vaccinated patients with similar clinical characteristics, who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four months after a confirmed COVID-19 infection. We measured (i) perfused boundary region (PBR) of the sublingual arterial (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) NTproBNP blood levels. Results Among vaccinated patients 54,2% had mild disease, 33,3% had moderate disease and 12,5% had severe disease, while among non-vaccinated 29,1% had mild disease, 32,9% had moderate disease and 38% had severe disease(p&amp;lt;0.05). At four months, vaccinated patients presented with higher LVGLS, GCW values and CFR compared to non-vaccinated (p&amp;gt;0.05 table), while GWI, GWW and GWE were similar between the two groups(p&amp;gt;0.5). Moreover, in vaccinated patients RVGLS and RV FWLS were significantly higher than in non-vaccinated patients (p&amp;gt;0.05). Also, NTproBNP leves were significantly lower in vaccinated than in non-vaccinated patients (p&amp;lt;0.05). At four months, in vaccinated patients , we observed a marginally lower brachial and central systolic blood pressure compared with non-vaccinated (p=0.045, p=0.048 respectively.) Vaccinated patients displayed similar FMD and PWV values compared to non-vaccinated (p&amp;gt;0.05 for all the comparisons). Conclusion Patients vaccinated against COVID-19 suffered from milder disease resulting to better cardiac function and lower NTproNP levels than non-vaccinated 4 months post COVID infection.

Diabetes, chronic respiratory and cardiovascular diseases in Germany and Europe (EHIS-3 Survey)

Abstract Background We examined the prevalence of major NCD groups (diabetes, chronic respiratory diseases (CRD) and cardiovascular diseases (CVD)) as well as self-rated health (SRH) and health-related limitation in everyday activities among those with one of these NCD in Germany and Europe (average of 28 European countries (EU-28)). Methods Data was derived from the European Health Interview Survey (EHIS-3, 2019/20). Health indicators were: self-reported diabetes, CRD and CVD in the past 12 months; SRH (very good/good vs. fair, bad, very bad) and health-related limitations in usual everyday activities for at least 6 months (severe/moderate vs. no limitation). Educational level was operationalized via ISCED-11. Analyses are age-standardized to the European Standard Population 2013. Results Prevalence of major NCD in Germany were statistically significantly higher than in the EU-28: diabetes 8.1% vs. 7.1%, CRD 11.2% vs. 7.9% and CVD 6.6% vs. 5.4%. Highest prevalence was observed in the lowest educational group and lowest prevalence in the highest educational group for all of these NCD in Germany as well as in the EU-28. The proportion of a very good/good SRH among people having one of these NCD was higher in Germany compared to the EU-28: for people with diabetes 35.8% vs. 31.0%, with CRD 45.6% vs. 42.9% and with CVD 25.3% vs.19.1%. The proportion of health-related limitations among those having at least one of these NCD varied according to educational level in Germany as well as in the EU-28 with a higher prevalence among people with low educational level compared to high. Conclusions Even though prevalence of these NCD were higher in Germany, a higher proportion of very good/good SRH for people with one of these NCD was observed compared to the EU-28. Many factors such as severity of disease, disease management and care could explain this difference. Social inequalities were present not only in the prevalence of NCD but also in health-related limitations in Germany and Europe. Key messages • Prevalence of self-reported major NCD were higher in Germany while self-rated health among people having NCD was better than in Europe. • Health equity interventions in Germany and Europe are necessary.

Assessment of surgical revascularization completeness with quantitative myocardial blood flow distribution derived from CCTA in severe coronary artery disease

Abstract Background Complete revascularization remained the "holy grail" in the treatment of patients with severe coronary artery disease (CAD). However, there is no universally accepted definition of complete revascularization after coronary bypass graft surgery (CABG). The current assessment methods are visual, categorical, and biased by the operator's intention. Moreover, no method to date provides an individualized quantification of residual ischemia burden. Purpose We aim to provide an individualized method to assess the completeness of surgical revascularization through quantitative myocardial blood flow distribution derived from coronary computed tomography angiography (CCTA) that could reflect the actual functional ischemia burden after CABG. Methods Patients with 3VD and/or left main CAD were enrolled in the first-in-human FAST TRACK CABG trial for surgical revascularization guided solely by CCTA and fractional flow reserve derived from CCTA (FFRCT). Following CABG, the study protocol mandated a 30-day follow-up CCTA, which provides graft patency and topographical adequacy of the bypass graft anastomoses. The pre- and post-CABG CCTA were analyzed. The FFRCT value and percent myocardial blood flow distribution (%MBF) were computed for all 16 SYNTAX score segments using the validated method of Keulards et al(1). On pre-CABG CCTA, the myocardium located distal to the site where the FFRCT value dropped below 0.80 on the vessel centerline was considered ischemic, and the %MBF of the subtended myocardium was summed into the total percent ischemic myocardium (Figure 1). Following CABG, the segment was considered adequately revascularized when a non-narrowed graft was anastomosed distally to the site of FFRCT≤0.8 on the pre-operative CCTA. The change in percent ischemic myocardium and the residual ischemic burden were calculated for each patient (Figure 2). Results CCTA, FFRCT, and %MBF were obtained pre- and post-CABG in 96 patients, and the percent ischemic myocardium was computed per patient. At baseline, the average percent ischemic myocardium was 72.0(19.1)%. Post-CABG, the residual percent ischemic myocardium was 13.6(15.1)%. Residual percent ischemic myocardium &amp;lt;10% was achieved in 44 patients (44.8%). The first diagonal branch(n=13), distal LCX(n=12), and the first obtuse marginal branch(n=10) were the most frequent segments not revascularized, which subtended an average MBF of 12.2(3.5)%, 16.7(8.4)%, and 11.3(7.3)%, respectively. The main reason for inadequate revascularization was surgical deferral, with graft occlusion accounting for only 13.6% of the residual ischemic segments. Conclusion Percent ischemic myocardium and the completeness of surgical revascularization can be assessed with CCTA-derived %MBF. This novel method allows clinicians to assess the individualized ischemia burden and the completeness of revascularization that could be incorporated into personalized CABG planning.Figure 1Figure 2