Assessing the impact of disease incidence and immunization on the resilience of complex networks during epidemics.

Disease severity through an immunized population ensconced on a physical network topology is a key technique for preventing epidemic spreading. Its influence can be quantified by adjusting the common (basic) methodology for analyzing the percolation and connectivity of contact networks. Stochastic spreading properties are difficult to express, and physical networks significantly influence them. Visualizing physical networks is crucial for studying and intervening in disease transmission. The multi-agent simulation method is useful for measuring randomness, and this study explores stochastic characteristics of epidemic transmission in various homogeneous and heterogeneous networks. This work thoroughly explores stochastic characteristics of epidemic propagation in homogeneous and heterogeneous networks through extensive theoretical analysis (positivity and boundedness of solutions, disease-free equilibrium point, basic reproduction number, endemic equilibrium point, stability analysis) and multi-agent simulation approach using the Gilespie algorithm. Results show that Ring and Lattice networks have small stochastic variations in the ultimate epidemic size, while BA-SF networks have disease transmission starting before the threshold value. The theoretical and deterministic aftermaths strongly agree with multi-agent simulations (MAS) and could shed light on various multi-dynamic spreading process applications. The study also proposes a novel concept of void nodes, Empty nodes and disease severity, which reduces the incidence of contagious diseases through immunization and topologies.

Clinical characteristics and risk factors associated with diverse manifestations of COVID-19 in patients aged 85 years and older.

Objective: The goal of this study is to assess the clinical attributes exhibited by patients aged 85 years and older who present different manifestations of COVID-19, and to examine the factors influencing the classification of the disease severity. Method: This retrospective study was conducted at a single center, encompassing an analysis of clinical data obtained from patients with COVID-19 admitted to a general geriatric hospital in Hangzhou, Zhejiang, China, during the period from December 20, 2022, to February 1, 2023. The study focused on 91 eligible patients whose disease severity was compared based on the imaging findings. Results: A total of 91 patients aged 85 years and older, with a median age of 92, including 46 males, 10 exhibiting mild symptoms, 48 moderate cases, and 33 severe cases met the inclusion criteria. Notably, disease severity displayed a significant correlation with age (p < 0.011). All patients presented with complicated chronic underlying conditions and a history of prolonged medication use. Rheumatic immune diseases (p = 0.040) and endocrine medications, primarily hypoglycemic agents (p = 0.034), exhibited statistical significance. Additionally, markers such as lactate dehydrogenase (LDH) (p = 0.030), interleukin 6 (IL-6) (p = 0.014), and D-dimer (p = 0.007) revealed significant associations with disease severity. Chest computed tomography scans predominantly revealed inflammatory features (n = 81, 89.0%). Notably, patients classified as having mild or moderate conditions exhibited eventual improvement, while 13 patients (39.4%) among the severe cases succumbed to the disease. Conclusion: The classification of disease among patients aged 85 years or older old is correlated with advanced age, concurrent rheumatic immune diseases, and prolonged administration of endocrine medications. Furthermore, patients with elevated levels of LDH, IL-6, and D-dimer demonstrated a higher propensity for developing severe diseases.

Patient-reported data on the severity of Von Willebrand disease.

INTRODUCTION: The severity of Von Willebrand disease (VWD) is currently based on laboratory phenotype. However, little is known about the severity of the patient's experience with the disease. The most recent VWD guidelines highlight the need for patient-reported outcomes (PROs) in VWD. AIM: The study aimed to investigate the patient-perspective on VWD severity and to identify key factors that determine the severity of disease experienced by patients. MATERIALS AND METHODS: Patients participated in a nationwide cross-sectional study on VWD in the Netherlands (WiN-study). Patients filled in a questionnaire containing questions on the experienced severity of VWD (4-point scale), bleeding score (BS) and quality of life (QoL). RESULTS: We included 736 patients, median age of 41.0 years (IQR 23.0-55.0) and 59.5% were women. A total of 443 had type 1, 269 type 2 and 24 type 3 VWD. Self-reported severity of VWD was categorized as severe (n = 52), moderate (n = 171), mild (n = 393) or negligible (n = 120). Classification by historically lowest FVIII:C levels < 0.20 IU/mL as a proxy for severe VWD aligned with patient-reported severity classification with a 72% accuracy. Type 3 VWD (OR = 4.02, 95%CI: 1.72-9.45), higher BS (OR = 1.09, 95%CI: 1.06-1.11), female sex (OR = 1.36, 95%CI: 1.01-1.83), haemostatic treatment in the year preceding study inclusion (OR = 1.53, 95%CI: 1.10-2.13) and historically lowest VWF:Act levels (OR = 0.26, 95%CI: 0.07-1.00) were independent determinants of patient-reported severity. CONCLUSION: This study shows that patient-reported data provide novel insights into the determinants of experienced disease severity. Our findings highlight the need for studies on PROs with validated questionnaires to assess the burden of VWD.

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome.

Purpose: This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets. Experimental Design: Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression. Results: ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity. Conclusions: Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.

Clinical Course of Coronavirus disease 2019 C-19 in Patients with Bronchiectasis.

Objective: Coronavirus disease 2019 (COVID-19) has affected the whole world and caused the death of more than 6 million people. The disease has been observed to have a more severe course in patients with chronic lung diseases. There are limited data regarding COVID-19 in patients with bronchiectasis. The aim of this article is to investigate the course of COVID-19 and factors affecting the clinical outcome in patients with bronchiectasis. Material and Methods: This study was conducted using the Turkish Adult Bronchiectasis Database (TEBVEB) to which 25 centers in Türkiye contributed between March 2019 and January 2022. The database consisted of 1035 patients, and COVID-19-related data were recorded for 606 patients. Results: One hundred nineteen (19.6%) of the bronchiectasis patients (64 female, mean age 57.3 ± 13.9) had COVID-19. Patients with bronchiectasis who developed COVID-19 more frequently had other comorbidities (P = .034). They also more frequently had cystic bronchiectasis (P = .009) and their Bronchiectasis Severity Index was significantly higher (P = .019). Eighty-two (68.9%) of the patients who had COVID-19 were followed up in the outpatient clinic, 27 (22.7%) in the inpatient ward and 10 (8.4%) patients in the intensive care unit. There tended to be a higher percentage of males among patients admitted to the hospital (P = .073); similarly, the mean age of the patients admitted to the hospital was also higher (60.8 vs 55.8 years for the outpatients), but these differences did not reach statistical significance (P = .071). Conclusion: In conclusion, this study showed that severe bronchiectasis, presence of cystic bronchiectasis and worse Bronchiectasis Severity Index are associated with the development of COVID-19, but not with the severity of infection.

Procalcitonin serum level in patients with pemphigus vulgaris: can it be used as an inflammatory biomarker?

Procalcitonin (PCT) is a peptide precursor of calcitonin, considered as an infection marker in many settings. Recently, a few studies reported its rise in some inflammatory processes such as still's disease, anaphylactic shock and Kawasaki disease. To investigate the serum level of PCT in patients with pemphigus vulgaris (PV) and examine the relationship between serum level of PCT and the severity of disease. A cross-sectional study was conducted on 50 patients with PV, visited at a tertiary care hospital from August 2021 to May 2023. After recording the demographic and clinical characteristics of patients, PCT level as well as CRP and ESR levels were measured and analyzed. The median ESR, CRP and procalcitonin serum level for the patients was 6.40 mm/hr, 11.00 mg/dL and 0.025 ng/ml, respectively. Considering the mean serum PCT level of normal population which is reported as < 0.1 ng/ml, its level among our patients was in a normal range. A significant and positive correlation was observed between procalcitonin and ESR, as well as CRP. In opposite to PCT, CRP and ESR levels showed a significant and positive correlation with disease severity (P values: 0.002 and < 0.001, respectively). Our findings suggest that PCT might not be useful as a biomarker of inflammatory milieu or prognostic factor in patients with PV without any infection.

IgG reactivity to different desmoglein-3 ectodomains in pemphigus vulgaris: novel panels for assessing disease severity.

Introduction: Pemphigus vulgaris (PV) is an autoimmune disease characterized by IgG autoantibodies targeting desmoglein-3 (Dsg3), leading to blistering of mucous membranes and skin. Although commercial ELISA kits effectively diagnose PV, correlation with clinical phenotype remains unclear. This study assesses multiple panels for monitoring disease severity and activity by profiling IgG autoantibodies against Dsg3's various extracellular ectodomains. Method: We designed and expressed different extracellular domains of Dsg3 in HEK293T cell line and developed 15 different ELISA panels, each using a single or multi ectodomains encompassing the entire extracellular region of Dsg3 to detect specific autoantibodies against the particular part of Dsg3. Results: To validate our approach, we compared our ELISA panel for the full Dsg3 (EC1-5) against a commercial kit using 154 random serum samples from PV patients, demonstrating a strong correlation. For evaluation of IgG autoantibody profiles in our panels, 59 PV patients were included, along with 11 bullous pemphigoid patients, and 49 healthy controls. For all the included subjects, 15 predefined ELISA panels were tested. The IgG autoantibodies against EC1 were detected in 86% of patients with a positive full Dsg3 ectodomain (EC1-5) ELISA, with 26% against EC2, 14% for EC3, 29% for EC4, and 23% for EC5. Among the panels with multiple Dsg3 ectodomains, EC1-3 and EC1-4 were representative of the entire Dsg3 ectodomain in terms of ELISA positivity across all included patients. A significant correlation (P<0.05) was observed between ELISA optical density (OD) and Pemphigus Disease Area Index (PDAI) scores in five panels, EC1, EC2-3, EC2-5, and EC3-4 in addition to the full ectodomain. It suggests an association with disease severity. Interestingly, while the ELISA panel for the entire Dsg3 extracellular ectodomains did not differentiate disease phases, in three of our panels, including EC1, EC3-5, and EC2-5, ANOVA analysis showed a statistically significant difference between the groups of patients in remission, partial remission or persistent lesions, and those with active disease (new cases or relapse). Among these three panels, EC1 was the only one that showed a significant difference in the multiple comparisons analysis; patients in the active phase had higher levels of autoantibodies than those in 'partial remission or persistent lesions' and 'complete remission' groups. Conclusion: The level of autoantibodies against EC1 was not only correlated with the full ectodomain but also associated with higher disease severity and active disease phase. This study indicates that a detailed autoantibody profile against Dsg3 ectodomains could serve as a marker for PV severity and activity which may potentially enhance early treatment initiation.

Study on the predictive value of laboratory inflammatory markers and blood count-derived inflammatory markers for disease severity and prognosis in COVID-19 patients: a study conducted at a university-affiliated infectious disease hospital.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), studies have found correlations between blood cell count-derived inflammatory markers (BCDIMs) and disease severity and prognosis in COVID-19 patients. However, there is currently a lack of systematic comparisons between procalcitonin (PCT), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR) and BCDIMs for assessing the severity and prognosis of COVID-19 patients. METHODS: A total of 1040 COVID-19 patients were included in the study. Demographics, comorbidities and laboratory results were analysed. BCDIMs refer to the following ratios: neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCR), systemic inflammation response index (SIRI) and systemic inflammation index (SII). Disease severity and 28-day mortality are clinical outcomes of this study. Area under the curve (AUC) of receiver operating characteristic (ROC) curve was calculated for these markers, and DeLong's test compared their statistical differences. Cox regression analysis assessed their predictive value for the 28-day mortality rate. RESULTS: Among the 1040 patients, 35.3% were severe/critical, 49.6% were moderate and 15.1% were mild cases. Within 28 days, 15.1% died. The NLR had the highest predictive value for disease severity (AUC: 0.790, 95% CI: 0.762-0.818). NLR differed significantly from other markers, except LCR. LCR best predicted 28-day mortality (AUC: 0.798, 95% CI: 0.766-0.829). Some markers showed significant differences in AUC with LCR. Multivariable Cox regression identified BCDIMs, PCT, CRP and CAR as significant risk factors for 28-day mortality. CONCLUSIONS: PCT, CRP, CAR and BCDIMs, easily obtained in clinical settings, are valuable predictors of disease severity and the 28-day mortality in COVID-19 patients. The NLR is particularly effective for disease severity, while the LCR is highly predictive of 28-day mortality. These markers provide guidance for stratified management of COVID-19 patients.

Pain in recessive dystrophic epidermolysis bullosa (RDEB): findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES).

BACKGROUND: Pain is common in the genetic skin fragility disorder epidermolysis bullosa (EB), from skin and mucosal injury and inflammation as well as extra-mucocutaneous sites. Individuals living with EB have identified pain as a priority for better treatments. OBJECTIVES: The Prospective EB Longitudinal Evaluation Study (PEBLES) is a prospective register study exploring the natural history of RDEB across all ages from birth to death. Here, we investigated the characteristics and treatment of pain in different RDEB subtypes. METHODS: Information was collected from individuals with different RDEB subtypes over an 8-year period. Data included visual analogue scale (VAS) ratings of background and procedural pain, its location, intensity and impact on sleep, as well as pain medication. Disease severity scores and quality of life measures were correlated to pain scores. RESULTS: Sixty-one participants (13 children, 48 adults) completed a total of 361 reviews. Pain was common, experienced by 93% of participants at index review, with 80% suffering both background and procedural pain. Across all RDEB patients, the median VAS for background pain was 40 (out of 100) [interquartile range 20,60] and for those having regular dressing changes, median procedural pain was 52 [40,80]. Severe (RDEB-S) and pruriginosa (RDEB-Pru) groups had the greatest increase in procedural compared to background pain of 20 and 22 VAS points, respectively. Correlations between disease severity and quality of life impairment were observed across most groups, particularly RDEB-S. Over half of those studied experienced pain frequently or constantly, and in one third pain disturbed sleep at least 4 nights per week. Skin was the commonest source of pain in all subtypes except inversa RDEB where the mouth was the main site. Despite frequent and severe pain, one third of participants used no medication for pain and, in those that did, pain levels remained high suggesting ineffectiveness of current pain management approaches and a significant unmet need in RDEB. CONCLUSION: The frequency, severity, and impact of pain in all RDEB patients is significant, particularly in RDEB-S and RDEB-Pru. Our findings highlight that current RDEB pain management is poorly effective and that further research is needed to address this symptom.

Regional cerebral blood flow in behavioral variant of FTD: hypoperfusion patterns and clinical associations.

BACKGROUND: Findings from functional neuroimaging techniques, such as single-photon emission computed tomography (SPECT), may add useful evidence improving Frontotemporal Dementia (FTD) diagnosis. The aim of the present study was to investigate patterns of hypoperfusion in a group of patients diagnosed with the behavioral variant of FTD (bvFTD) and to explore the relationship between brain perfusion and clinical characteristics. MATERIALS AND METHODS: Brain perfusion of 23 bvFTD patients was measured with SPECT scintigraphy in lobes and Brodmann areas (BAs) and the NeurogamTM software was used for image analysis. To assess behavioral disturbances and dementia severity, patients' informants completed the Frontotempotal Behavioral Inventory and the Frontotemporal Dementia Rating Scale. Descriptive statistics were used for the detection of pathological hypoperfusion in lobes and selected BAs. Associations among patients' clinical characteristics and perfusion in lobes were explored via non-parametric correlations. RESULTS: Participants presented pathological hypoperfusion in frontal, limbic and temporal lobes. The most prominent deficit was observed in limbic lobes, where all participants showed pathological hypoperfusion. Decreased perfusion was also observed in limbic, frontal and temporal BAs. Perfusion in the left and right frontal lobe was associated with behavioral disturbances and disease severity, which was also correlated with perfusion in right limbic, left and right temporal areas. CONCLUSION: Patterns of limbic, frontal and temporal hypopefusion were reported in the present study, along with associations between brain perfusion, behavioral disturbance and severity of dementia. Perfusion patterns can help to understand further associated brain biomarkers, contributing to early diagnosis and intervention in bvFTD.

miR-132-3p downregulates FOXO1 in CD4+ T cells and is associated with disease manifestations in patients with lupus.

OBJECTIVE: This study aimed to evaluate the expression status of miR-132-3p in CD4+ T cells in patients with systemic lupus erythematosus (SLE) and explore its potential role in SLE development. METHODS: The study included 60 patients with SLE and 30 healthy controls. miR-132-3p expression in CD4+ T cells was detected by real-time quantitative reverse transcription polymerase chain. Bioinformatics analyses were employed to predict target genes and explore the potential role of miR-132-3p. The associations between miR-132-3p levels and SLE Disease Activity Index (SLEDAI) score, as well as laboratory characteristics, were analyzed. RESULTS: miR-132-3p levels in CD4+ T cells were significantly higher in patients with SLE compared with healthy controls. Bioinformatics analysis identified FOXO1 as a potential target gene of miR-132-3p, with a particular emphasis on the FOXO signaling pathway. miR-132-3p up-regulation in CD4+ T cells was associated with high SLEDAI score, high anti-double-stranded DNA levels, low C3 and C4 levels, positive anti-ribosomal P, and high 24-hour urinary protein levels in patients with SLE. CONCLUSIONS: miR-132-3p may contribute to CD4+ T cell dysregulation during SLE by targeting FOXO1 and could potentially be used to assess disease severity.

Determinant Factors of Disease Severity for Patients With Hidradenitis Suppurativa Evaluated in a Spanish Hospital Over a 5-Year Period. / [Artículo traducido] Factores determinantes de la severidad de la enfermedad en los pacientes con hidradenitis supurativa evaluados en un hospital español durante un periodo de 5 años.

It is necessary to identify which factors or comorbidities are associated with more severe hidradenitis suppurativa, aiming to identify which patients may benefit more from early systemic treatment or a more aggressive approach. A retrospective study was conducted, including patients diagnosed with HS at the dermatology department of a Spanish hospital over a 5-year period. A total of 322 patients were included. A relationship was found between diagnostic delay, the presence of acne conglobata, pilonidal sinus, cardiovascular risk factors (hypertension, dyslipidemia, and/or diabetes mellitus) and more severe HS. No significant relationship was found between psychiatric comorbidities and the severity of the HS. The presence of perianal or truncal involvement was significantly associated with severe HS. Female sex and the presence of a family history of HS were associated with an earlier onset of the disease.

Unveiling Immunological and Hematological Markers in COVID-19: Insights from a Clinical Study.

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

-AI-assisted diagnostic potential of CT in bone oncology and its impact on clinical decision-making for intensive care.

Objective: This study evaluates the AI-assisted diagnostic potential of computed tomography (CT) for bone cancer and its influence on patient care during the pre- and post-treatment phases. It compares patient management approaches based on CT severity levels and identifies distinct CT phenotypes linked to disease severity. Methodology: We retrospectively examined 50 patients diagnosed with bone cancer between December 2022 and June 2023. The CT scans were analyzed according to the Radiological Society of North America (RSNA) guidelines. This study was performed using the deep convolutional neutral network (DCNN) model to assist doctors in diagnosing bone tumors through CT scanning. Patients' management approaches were compared based on the severity levels indicated by CT scans. Results: Fifty patients participated in this study, with a median age of 67.2 years, ranging from 32 to 89 years. Of them, 38 % were female and 62 % were male. In 2022, 19 individuals (13 males and 6 females, ages 32 to 84) were assessed, with a mean age of 59.9 years. In 2023, 31 individuals, aged 54 to 89 with a mean age of 71.6 years, were assessed; among them were 18 men and 13 women. SPECT scans revealed the following key diagnostic features: 85.9 % of patients exhibited bone lesions with ground-glass opacities, 88 % had multipolar involvement, 92.8 % had bilateral involvement, and 92.8 % showed peripheral involvement. The severity scores based on CT scans were significantly higher in patients requiring intensive care, with scores above 14 being more common in this group. Conclusion: Distinct CT findings during the AI-assisted diagnosis and treatment of bone cancer provided prompt and sensitive examination capabilities. Notably, two CT phenotypes emerged, associated with large consolidation patterns and high severity scores, offering crucial insights into disease severity and aiding in clinical decision-making for intensive care requirements. The study underscores the importance of CT in the effective monitoring and management of bone cancer pre- and post-treatment.

Dynamics of Spike-Specific Neutralizing Antibodies Across Five-Year Emerging SARS-CoV-2 Variants of Concern Reveal Conserved Epitopes that Protect Against Severe COVID-19.

Since early 2020, several SARS-CoV-2 variants of concern (VOCs) continue to emerge, evading waning antibody mediated immunity produced by the current Spike-alone based COVID-19 vaccines. This caused a prolonged and persistent COVID-19 pandemic that is going to enter its fifth year. Thus, the need remains for innovative next generation vaccines that would incorporate protective Spike-derived B-cell epitopes that resist immune evasion. Towards that goal, in this study we (i) Screened the sequences of Spike among many VOCs and identified conserved and non-conserved linear B-cell epitopes; (ii) Compared titers and neutralization antibodies specific to these conserved and non-conserved B-cell epitopes from serum of symptomatic and asymptomatic COVID-19 patients that were exposed to multiple VOCs across the 5-year COVID-19 pandemic, and (iii) Compared protective efficacy of conserved versus non-conserved B-cell epitopes against the most pathogenic Delta variant in a "humanized" ACE-2/HLA transgenic mouse model. We found robust conserved B-cell epitope-specific antibody titers and neutralization in sera from asymptomatic COVID-19 patients. In contrast, sera from symptomatic patients contained weaker antibody responses specific to conserved B-cell epitopes. A multi-epitope COVID-19 vaccine that incorporated the conserved B-cell epitopes, but not the non-conserved B-cell epitopes, significantly protected the ACE2/HLA transgenic mice against infection and COVID-19 like symptoms caused by the Delta variant. These findings underscore the importance of conserved B-cell epitopes in generating robust protective immunity against severe COVID-19 symptoms caused by various VOCs, providing valuable insights for the development of broad-spectrum next generation Coronavirus vaccines capable of conferring cross-variant protective immunity.

Association between plant-based dietary index and disease severity in patients with ulcerative colitis: a cross-sectional study.

BACKGROUND: Plant foods are naturally rich in anti-inflammatory nutrients. In this cross-sectional study, we assessed the association between the plant-based dietary index (PDI) and Mayo score in patients with ulcerative colitis (UC). METHODS: This analytical cross-sectional study included 158 patients with UC. The Mayo score was used to determine disease severity. An expert nutritionist performed the anthropometric assessments. A 168-item quantitative food frequency questionnaire (FFQ) was used to calculate the PDI, healthy PDI (hPDI), and unhealthy PDI (uPDI). To assess the association between the total Mayo score (as a dependent factor) and different indices of PDI (as an independent variable), the linear regression model was used. RESULTS: The mean age of participants was 42.52 ± 12.61 years. There were significant differences in the total Mayo score between tertiles of PDI score (p = 0.02). The result of linear regression showed that in the unadjusted model, compared with the patients in the first tertile of PDI, the patients in the second (-0.21 (-1.89, -0.17)), and third tertile (-0.21 (-1.95, -0.16)) had significantly lower total mayo scores. The inverse association remained significant after adjusting for covariates. However, uPDI and hPDI tertiles were not significantly associated with total Mayo scores in the adjusted and unadjusted models. CONCLUSION: higher PDI was significantly associated with higher UC severity. However, considering the limitations of the study, more cohort studies are needed to confirm these results.

Time preference shifts in medical decision-making after serious illness.

This study explores the impact of serious illnesses, such as cancer, on patients' time preferences in medical decision-making. Specifically, we assess how patients value extending their lifespan by one year under varying survival prognoses through three experimental studies. The findings reveal that patients exhibit a higher Subjective Discount Rates (SDR) in their medical decisions after a serious illness diagnosis. Notably, this difference in individual health also affects the time preferences of their family members. Additionally, the subjective contextual setting of the illness can also increase an individual's SDR levels. The research highlights a tendency for patients and families facing a potential short life expectancy to focus more on immediate concerns, leading to potentially shortsighted and irrational medical choices. This behavior often results in regret during the end-of-life stage. These insights are vital for healthcare professionals in optimizing treatment plans and for policymakers in understanding patient behaviors more comprehensively. The study emphasizes the need for considering psychological and behavioral changes in patients grappling with severe health challenges.

Discrepancies between Coronary Artery Calcium Score and Coronary Artery Disease Severity in Computed Tomography Angiography Studies.

The aim of this paper is to demonstrate the difference in usefulness of the coronary artery calcium score (CACS) and the full assessment of the severity of coronary artery disease in coronary computed tomography angiography (CCTA) studies. The difference between the population risk of coronary artery disease (CAD) assessed by the CACS and the severity of CAD was demonstrated in images from two CCTA studies. The first image is from a patient with a CACS of 0 and significant coronary artery stenosis. In the native phase of CCTA examination, no calcified changes were detected in the topography of the coronary arteries. In the middle section of the left descending artery (LAD), at the level of the second diagonal branch (Dg2), a large non-calcified atherosclerotic plaque was visible. Mid-LAD stenosis was estimated to be approximately 70%. The second image features a patient with a high CACS but no significant coronary artery stenosis. The calcium score of individual coronary arteries calculated using the Agatston method was as follows: left main (LM) 0, LAD 403, left circumflex (LCx) 207.7, right coronary artery (RCA) 12. CACS was 622.7, representing a significant population risk of significant CAD. In the proximal and middle sections of the LAD, numerous calcified and mixed atherosclerotic plaques with positive remodeling were visible, causing stenosis of 25-50%. Similarly, in the proximal and middle sections of the LCx, numerous calcified and mixed atherosclerotic plaques with positive remodeling were visualized, causing stenoses of 25-50%. Calcified atherosclerotic plaques were found in the RCA, causing stenosis <25%. The entire CCTA image met CAD-RADS 2 (coronary artery disease reporting and data system) criteria. In summary, CACS may be applicable in population-based studies to assess the risk of significant CAD. In the evaluation of individual patients, a comprehensive assessment of CAD severity based on the angiographic phase of the CCTA examination should be used.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019.

OBJECTIVES: Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. METHODS: Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. RESULTS: We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83). DISCUSSION: PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

Systemic immune-inflammation index combined with pediatric appendicitis score in assessing the severity and prognosis for paediatric appendicitis.

BACKGROUND: Pediatric appendicitis is a common cause of abdominal pain in children and is recognized as a significant surgical emergency. A prompt and accurate diagnosis is essential to prevent complications such as perforation and peritonitis. AIM: To investigate the predictive value of the systemic immune-inflammation index (SII) combined with the pediatric appendicitis score (PAS) for the assessment of disease severity and surgical outcomes in children aged 5 years and older with appendicitis. METHODS: Clinical data of 104 children diagnosed with acute appendicitis were analyzed. The participants were categorized into the acute appendicitis group and chronic appendicitis group based on disease presentation and further stratified into the good prognosis group and poor prognosis group based on prognosis. The SII and PAS were measured, and a joint model using the combined SII and PAS was constructed to predict disease severity and surgical outcomes. RESULTS: Significant differences were observed in the SII and PAS parameters between the acute appendicitis group and chronic appendicitis group. Correlation analysis showed associations among the SII, PAS, and disease severity, with the combined SII and PAS model demonstrating significant predictive value for assessing disease severity [aera under the curve (AUC) = 0.914] and predicting surgical outcomes (AUC = 0.857) in children aged 5 years and older with appendicitis. CONCLUSION: The study findings support the potential of integrating the SII with the PAS for assessing disease severity and predicting surgical outcomes in pediatric appendicitis, indicating the clinical utility of the combined SII and PAS model in guiding clinical decision-making and optimizing surgical management strategies for pediatric patients with appendicitis.