Search Results (11,530)

Background: Long-acting monoclonal antibodies have become an important strategy for preventing respiratory syncytial virus (RSV) disease in infants. Nirsevimab is the first product for which substantial post-licensure implementation data are available, whereas real-world evidence on clesrovimab remains limited. Although nirsevimab has demonstrated high efficacy, its uptake varies considerably across countries, healthcare systems, delivery settings, and population subgroups. This World Association for Infectious Diseases and Immunological Disorders (WAidid) consensus document examines the policy, organizational, economic, and equity-related determinants that shape real-world implementation of long-acting monoclonal antibodies for infant RSV prevention. Methods: This study was conducted as a structured narrative review and WAidid expert consensus document. A structured literature search was performed in PubMed and Embase for English-language publications relevant to nirsevimab uptake and implementation, complemented by targeted review of surveillance reports, policy documents, and public health guidance from the ECDC, UKHSA, and CDC, as well as reference lists of selected publications. Eligible sources included observational and real-world implementation studies, systematic reviews and meta-analyses, economic evaluations, guidelines, policy statements, surveillance reports, and relevant narrative reviews. Evidence was synthesized qualitatively according to policy frameworks, financing and reimbursement, delivery pathways, demographic and socioeconomic determinants, and healthcare-system factors influencing uptake. No statistical software was used because no quantitative re-analysis or meta-analysis was performed. Results: Nirsevimab uptake was strongly influenced by national RSV prevention policies, particularly whether countries adopted universal infant monoclonal antibody programs, maternal RSV vaccination strategies, dual maternal–infant approaches, or targeted risk-based models. Universal, publicly funded programs integrated into neonatal care achieved the highest and most homogeneous coverage, especially when administration occurred before hospital discharge and was supported by registry-based recall systems for infants born outside the RSV season. In contrast, fragmented, outpatient-only, insurance-dependent, or partially reimbursed models were associated with lower, delayed, or more variable uptake. Additional determinants included product cost, reimbursement pathways, provider practices, caregiver awareness and health literacy, insurance status, income, race and ethnicity, geographic deprivation, and access to primary pediatric care. Most available evidence comes from high-income countries, limiting generalizability to low- and middle-income settings, where RSV burden is greatest and implementation constraints may differ. Conclusions: Successful implementation of long-acting monoclonal antibodies for infant RSV prevention requires more than regulatory approval and demonstrated efficacy. Equitable uptake depends on clear national recommendations, sustainable public financing, reliable product supply, integration into neonatal and primary pediatric care, proactive identification and recall of eligible infants, and targeted strategies to reduce socioeconomic and geographic disparities. Although many determinants identified in high-income settings are likely relevant globally, their feasibility, relative importance, and impact require dedicated evaluation in low- and middle-income countries. Full article

Background: The absence of coronary artery calcium (CAC = 0) on computed tomography (CT) portends a low but not zero coronary risk. However, the frequency and prognostic significance of non-calcified plaques in CAC = 0 patients are incompletely defined, and non-coronary artery disease (CAD) causes of coronary risk have been proposed. We sought to define the ischemic burden, CAD status, and outcomes of CAC = 0 patients. Methods: The Intermountain electronic medical records were searched for CAC = 0 patients undergoing stress positron emission tomography (PET)/CT between January 2016 and July 2022. We defined definite PET abnormality as ischemic burden (IB) ≥ 10%. Patients were followed for angiographic findings, interventions, and major adverse cardiovascular events (MACE) over 3.1 ± 1.3 years. Results: Of 22,542 PET/CT studies in primary prevention patients, 5054 (22.4%) had CAC = 0. Of these, 59 (1.2%) had IB ≥ 10% on PET. Selective coronary angiography was performed within 90 days in 25 (42%) of IB ≥ 10% patients. Severe CAD was present in 11, but findings were not explained by CAD in 14. Revascularization was indicated in 10 (16.9%) of 59 with IB ≥ 10% vs. 0.04% of IB = 0% (p < 0.0001); 3-year outcomes also were lower with IB = 0%. Conclusions: In this large series of stress PET/CT study data, IB ≥ 10% in patients with CAC = 0 was rare. Most positive PET tests were not explained by obstructive CAD. While CAC does not perfectly predict an absence of coronary ischemia or obstructive CAD, it is a strong marker of prognosis. Here, we show that IB by PET supplements CAC score to importantly refine risk assessment. Full article

Heritability in Parkinson’s disease (PD) may be driven by rare variants (RVs), but genetic data for Chinese cohorts remain limited. We investigated the relationship between RVs and the risk and phenotype of PD by performing targeted exome sequencing of 29 PD candidate genes in 311 late-onset, sporadic Chinese PD patients and 699 local controls. A total of 174 RVs (that were likely deleterious using in silico prediction tools) were identified in 27 of the 29 genes sequenced. Mean RV burden was higher (1.178 vs. 0.478, p = 1.26 × 10⁻²⁴) and HLA-DRB5 p.Val104ArgfsTer26 was enriched in PD patients (0.207 vs. 0.000, p < 0.0003) compared with controls. Gene-based RV carrier status in PD patients was then examined for correlation with phenotypic characteristics. The RV carrier status of LRRK2 and HLA-DRB5 was associated with tremor, SREBF1 with gait disturbance, and SYNJ1 and SCARB2 with motor fluctuations. Earlier onset age and neuropsychiatric symptoms were associated with GBA1 variants. Olfactory deficit, autonomic disturbance, anxiety and depression were associated with variants in SLC44A1, HLA-DRB5, and SCARB2 respectively. Our results demonstrated a prominent RV burden in Chinese PD and illustrated the importance of genetic influence on the risk and phenotype of sporadic PD. Further studies are warranted to correlate these genes with putative pathogenic pathways. Full article

Coffee is deeply embedded in Saudi culture and is among the most consumed beverages worldwide. However, contamination by toxic heavy metals may represent an underrecognized public health concern, particularly in regions already burdened by diabetes mellitus and cardiovascular disease. This study evaluated concentrations of lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr), and nickel (Ni) in 21 commercial coffee samples representing seven product categories marketed in Saudi Arabia. Samples were prepared using EPA Method 3050B acid digestion and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Health risks were assessed through estimated daily intake (EDI), hazard quotient (HQ), hazard index (HI), and incremental lifetime cancer risk (ILCR) using USEPA exposure parameters and Saudi-specific coffee consumption data. All metals were detected in every sample. Mean concentrations (mg/kg dry weight) were 1.638 for Pb, 0.560 for Cd, 0.622 for Cr, 0.536 for Ni, and 0.034 for As. Cadmium exceeded the European Union maximum limit for roasted coffee in all samples, while elevated Pb levels were observed in dark roast and Yemeni coffees. Although the overall non-carcinogenic risk remained below the accepted threshold (HI = 0.438), the combined ILCR for As, Cd, and Pb was 5.84 × 10⁻⁵. Inclusion of a conservative screening-level chromium contribution, calculated by assuming that all measured total Cr was present as Cr(VI), increased the upper-bound total ILCR to 9.38 × 10⁻⁵. This value remained within, but approached the upper boundary of, the risk-management range applied in this study. These findings highlight the need for strengthened monitoring and regulatory control of coffee products in Saudi Arabia. Full article

Background/Objective: Albumin has emerged as a prognostic marker across cardiovascular disease, but its independent association with heart failure (HF) in different clinical settings remains scarce. This study investigated the prognostic impact of baseline albumin levels in patients undergoing coronary angiography (CA) for different indications. Methods: Consecutive inpatients undergoing CA from 2016 to 2022 were retrospectively included at one institution and stratified into quartiles according to baseline albumin levels (Q1: <30, Q2: 30–34, Q3: 34–37, Q4: >37 g/L). The primary endpoint was rehospitalization for HF at 36 months; secondary endpoints were coronary revascularization and acute myocardial infarction (AMI). Statistical analyses included Kaplan–Meier and Cox regression analyses. Results: A total of 7520 patients were included (median albumin: 34.3 g/L; IQR: 30.5–37.2 g/L). Lower albumin levels were associated with a higher comorbidity burden and more extensive coronary artery disease (three-vessel disease: Q1: 36.1% vs. Q4: 21.4%; p = 0.001). HF-related rehospitalization at 36 months increased progressively with lower albumin (Q1: 28.4% vs. Q2: 25.1% vs. Q3: 21.0% vs. Q4: 13.9%; p = 0.001). After multivariable adjustments, the lowest albumin group (<30 g/L) remained independently associated with HF-related rehospitalization (HR = 1.381; 95% CI: 1.105–1.727; p = 0.005), whereas no independent association with coronary revascularization or AMI was demonstrated. The association was most evident in patients ≥70 years of age and in those with left ventricular ejection fraction (LVEF) ≥ 35%. Conclusions: In unselected patients undergoing CA, lower albumin levels independently predicted the HF-related rehospitalization at 36 months, but not coronary revascularization or AMI. Routine albumin measurement may provide meaningful prognostic information in patients undergoing CA. Full article

Background/Objectives: Anal squamous cell carcinoma (SCCA) is a rare Human Papillomavirus (HPV)-related disease in the general population but its incidence is increasing among high-risk populations, i.e., men who have sex with men (MSM), HIV+ patients and women with a history of cervical/vulvar dysplasia. The objectives of this study were: (i) to investigate the prevalence of high-risk (HR) and low-risk (LR) anal HPV infections in a high-risk cohort; (ii) to correlate specific HPV genotypes with cytological and histological outcomes; and (iii) to assess the impact of cumulative HPV genotype burden. Methods: A retrospective study (2017–2022) was conducted on 550 high-risk patients. All patients underwent anal Pap tests (ThinPrep, Hologic) and HPV genotyping (Anyplex II HPV 28, Seegene), according to our screening protocol. High-Resolution Anoscopy (HRA) was performed on 430 patients; biopsy was performed in all cases with suspicious lesions. Results: The overall HR-HPV prevalence was 57.3%. Men showed a significantly higher prevalence of HR-HPV (59.9% vs. 47.4%) and cytological abnormalities (35.8% vs. 20.2%) compared to women. Notably, HPV 16, 58 and 45 accounted for 79% of AIN2+ (Anal Intraepithelial Neoplasia of grade 2 or higher) lesions. A significant cumulative HPV genotype burden effect, i.e., the number of HPV genotypes detected, was observed: patients with ≥3 HR-HPV types showed an increased risk of AIN2+ lesions (aOR 34.72; 95% CI 4.07–296.10) and AIN1+ lesions (aOR 16.26; 95% CI 4.54–58.30) respectively. The presence of ≥3 LR-HPV genotypes in HR-HPV-positive patients is associated with an increased risk of AIN1 lesions. Conclusions: HPV 16, 58 and 45 positivity and the cumulative HPV genotype burden could represent new potential indicators for risk stratification in high-risk populations. Future larger-scale prospective studies are needed to validate these preliminary results. Full article

Women of reproductive age diagnosed with thyroid cancer face a distinctive psychological burden arising from the concurrent demands of disease management and primary caregiving, yet the mechanisms linking parenting stress to diminished well-being in this group remain poorly characterized. The present study applied a stress-buffering framework to examine whether psychological distress (anxiety and depressive symptoms) statistically mediated the association between parenting stress and well-being, and whether social support attenuates these pathways. We recruited a convenience sample of 400 consecutive eligible mothers between July and December 2025 at a tertiary cancer center in China. All were of reproductive age (18–49 years), had cytologically confirmed papillary thyroid carcinoma and at least one child aged ≤12 years, and completed the survey during their initial hospitalization, before surgery. Validated instruments assessed parenting stress, anxiety and depression, social support, and well-being; analyses included bivariate correlations, mediation, and moderated mediation models. Well-being correlated inversely with parenting stress (r = −0.447, p < 0.01) and anxiety and depression (r = −0.573, p < 0.01), and positively with social support (r = 0.515, p < 0.01). Psychological distress partially mediated the parenting stress–well-being association, with the indirect effect constituting 44.32% of the total effect (−0.210, 95% CI: −0.321 to −0.125). Parenting stress was positively associated with HADS scores (β = 0.322, p < 0.001), though this association was weaker at higher levels of social support (interaction β = −0.106, p = 0.006). Both parenting stress (β = −0.148, p = 0.001) and HADS scores (β = −0.367, p < 0.001) were independently associated with lower well-being, while social support moderated the parenting stress–well-being association (interaction β = 0.098, p = 0.003). In conclusion, parenting stress and psychological distress were jointly associated with diminished well-being in this population, but social support emerged as a modifiable protective correlate. Psychosocial interventions targeting stress reduction, emotional regulation, and support mobilization may thus hold particular promise for improving outcomes among young women with thyroid cancer. Full article

Malaria pathogenesis results from a complex interplay among parasite burden, inflammation, and oxidative stress, all of which contribute to disease severity. This study evaluated the antimalarial, immunomodulatory, and antioxidant effects of a suspension of powdered aerial parts of Artemisia mexicana (A. mexicana) suspended in 0.5% carboxymethylcellulose (CMC), using a murine model of cerebral malaria. Male CBA/Ca mice were infected with Plasmodium berghei ANKA and treated with A. mexicana. Disease progression was evaluated through parasitemia, haemoglobin levels, body weight and temperature. Immunomodulatory effects were assessed by analysing splenic immune cell populations and pro- and anti-inflammatory cytokines, while antioxidant activity was determined in brain and spleen tissues. Treatment reduced parasitemia in a dose-dependent manner, with the highest efficacy observed at 1600 mg/kg, and also prevented haemoglobin loss and body weight decline. A. mexicana preserved CD4⁺ (T-helper) and CD8⁺ (T-cytotoxic) T-cell populations and modulated cytokine responses, increasing IFN-γ, IL-17, and IL-10 levels. Additionally, treatment increased glutathione peroxidase activity in the brain and spleen without affecting lipid peroxidation. These findings demonstrate that A. mexicana exerts antimalarial and immunomodulatory effects and modulates antioxidant responses, suggesting that the regulation of inflammation and redox balance contributes to improved outcomes during malaria infection. Full article

Asthma is one of the most prevalent chronic respiratory diseases worldwide, and environmental pollutants such as desert dust play a significant role in triggering respiratory sensitization and aggravating asthma symptoms. In this study, a mathematical model is proposed to investigate the dynamics of dust-induced asthma progression. The population is divided into unaware susceptible individuals, aware susceptible individuals, dust-sensitized individuals, and asthmatic individuals, while two additional variables describe dust concentration in the human population and the environment. Fundamental qualitative properties of the model, including positivity, boundedness, existence of equilibria, and stability conditions, are established. It is shown that the asthma-free equilibrium is locally and globally asymptotically stable whenever the dust-induced asthma threshold is below unity, whereas a unique asthma-persistent equilibrium exists when the dust-induced asthma threshold exceeds unity. To reduce the burden of asthma, an optimal control problem is formulated by incorporating three time-dependent interventions: awareness campaigns, medical intervention for dust-sensitized individuals, and environmental dust reduction. Pontryagin’s Maximum Principle is employed to characterize the optimal controls and derive the corresponding adjoint system. Numerical simulations, performed using the forward–backward sweep method, demonstrate that the proposed interventions significantly reduce the number of asthmatic individuals compared with the uncontrolled case. Furthermore, a cost-effectiveness analysis based on the Average Cost-Effectiveness Ratio (ACER) and Incremental Cost-Effectiveness Ratio (ICER) is conducted to compare seven intervention strategies. The results indicate that the medical intervention strategy is the most economically attractive option, while the combined strategy involving all controls achieves the largest reduction in asthma burden. Full article

Strongyloidiasis is a neglected, potentially lifelong disease caused by Strongyloides stercoralis that can lead to a high mortality rate in immunocompromised hosts; therefore, it is necessary to increase the accuracy of infection diagnosis. In the current study, we used Wistar rats experimentally infected with different burdens of Strongyloides venezuelensis to characterize circulating leukocytes and IgM, IgG, IgG1, IgG2a, and IgA reactivity before and after anthelmintic treatment or immunosuppression. Infection, especially with 500 L3, induced an increase in circulating leukocytes, particularly during the acute phase. Animals treated with ivermectin showed complete elimination of the parasite and an early reduction in circulating eosinophils. The production of IgM, IgG, and IgG1 anti-L3 (infective larvae) and anti-Sv (adult worm) antigens was significantly elevated in all infected groups but did not allow differentiation between cured and infected animals. Treatment with dexamethasone delayed worm elimination and temporarily reduced cellular response and parasite-specific IgG production but did not alter IgM reactivity. IgG2a anti-L3 and anti-Sv reactivity showed a progressive reduction, returning to baseline levels in ivermectin-treated rats. IgA anti-ES/L3 (excretory and secretory larval antigens) reactivity significantly decreased in intestinal wash after parasitological cure. These data would help the development of more efficient immunodiagnostic alternatives for human strongyloidiasis based on antibody isotype reactivity. Full article

Osteonecrosis can cause significant and chronic musculoskeletal morbidity in children and adolescents with sickle cell disease (SCD). Although the femoral head is most frequently affected, lesions can also occur in the humeral head, vertebral bodies, knees, and other joints. Progressive joint damage can result in chronic pain, impaired mobility, loss of function, and the need for surgical intervention at a young age. As survival continues to improve in SCD, the long-term burden of osteonecrosis is becoming increasingly important. This narrative review summarizes the current understanding of osteonecrosis in pediatric and adolescent SCD. We review its epidemiology, pathophysiology, clinical presentation, imaging findings, and management. Disease burden increases with age and is closely linked to markers of severe SCD, including frequent vaso-occlusive crises and acute chest syndrome. Full article

Background/Objectives: Immune-mediated inflammatory skin diseases (IMSDs), including psoriasis, atopic dermatitis, and systemic sclerosis, are chronic relapsing disorders that impose substantial physical, psychological, and economic burdens. Current assessment relies largely on subjective clinical scoring and conventional imaging modalities that provide limited functional information. This structured narrative review evaluates photoacoustic imaging (PAI) as a non-invasive optical-ultrasound technique for morphological and functional assessment in IMSDs. Methods: We searched PubMed studies published from January 2017 to December 2025 using terms related to photoacoustic imaging, optoacoustic mesoscopy, psoriasis, atopic dermatitis, systemic sclerosis, contact dermatitis, and immune-mediated inflammatory skin disease. Studies were narratively synthesized by disease, PAI modality, comparator, outcome, and translational limitation. Main Findings: PAI can map vascular and pigment-related optical absorption and estimate oxygenation, blood volume, and selected structural biomarkers. In psoriasis, atopic dermatitis, and systemic sclerosis, PAI-derived measures have been associated with clinical severity, subclinical vascular or epidermal changes, and treatment response. However, most available studies are small, single-center, heterogeneous, or based on prototype systems, and several biomarkers still require histopathological and external validation. Conclusions: Current evidence supports PAI as a feasible research and potential adjunctive assessment tool for IMSDs rather than an established replacement for standard clinical, histopathological, or imaging methods. Standardized protocols, validation across skin phototypes, cost-effective devices, and prospective multicenter studies are required before routine clinical adoption. Full article

Chronic illness burden is unevenly distributed across US counties, with some counties experiencing overlapping challenges related to healthcare access, socioeconomic disadvantage, environmental exposure, and chronic disease burden. Several multidimensional frameworks, including the Social Vulnerability Index, Environmental Justice Index, and Pandemic Vulnerability Index, have highlighted the importance of integrating multiple determinants of vulnerability. This study presents an interpretable machine learning-based multi-model framework for constructing and characterizing a county-level chronic illness vulnerability index. The framework integrates five domains: health burden, social conditions, environmental exposure, behavioral factors, and COVID-19-related measures. Four publicly available 2023 datasets were merged into a 12-feature dataset covering 2911 US counties, and a weighted domain score was used to classify counties into low-, medium-, and high-vulnerability categories. Because the class labels were constructed directly from these variables, the resulting categories should be interpreted as an author-defined composite index rather than an independent health outcome. Four machine-learning models, including Random Forest, XGBoost, MLP (Multilayer Perceptron), and TabNet, were evaluated individually and as a majority-vote ensemble. SHAP and LIME were independently applied to interpret model behavior, and the explainability analyses were restricted to model interpretation rather than causal inference. The ensemble reproduced the three-tier classification with an accuracy of 94.68% and an ROC-AUC (Receiver Operating Characteristic–Area Under the Curve) of 0.9974 on 583 held-out counties. Because the class label is a deterministic function of the same 12 features, these results should be interpreted as measures of index reconstruction rather than prediction of an independent outcome; a penalized multinomial logistic regression achieved 98.97% reconstruction accuracy, further indicating the largely linear structure of the index. COPD prevalence ranked first according to both SHAP and LIME across all four models, reflecting the weighting structure of the index rather than an independent causal effect. Six of the twelve features received identical rankings from both methods, and no feature moved more than three positions. The framework relies entirely on publicly available data and provides a reproducible approach for county-level characterization of chronic illness vulnerability. Full article

Chronic hepatitis C virus (HCV) infection is an established risk factor for B-cell lymphoproliferative disorders and represents a paradigmatic model of infection-driven lymphomagenesis. Although direct-acting antivirals have markedly reduced the burden of HCV-related disease, HCV-associated lymphomas continue to occur. Moreover, HCV screening remains incomplete in some geographical areas and healthcare settings, leaving a substantial proportion of infected individuals unaware of their status. This narrative review integrates current evidence on the mechanisms linking chronic HCV infection to mixed cryoglobulinemia and overt B-cell non-Hodgkin lymphoma. HCV lymphotropism and persistent antigenic stimulation could initially promote the selection and expansion of autoreactive B-cell clones, while mixed cryoglobulinemia represents the most informative pre-lymphomatous risk condition. Cytokine-mediated survival signals, particularly those involving B-cell activating factor, reinforce clonal persistence and cooperate with host genetic susceptibility, impaired apoptotic control, and activation-induced cytidine deaminase-mediated genomic instability. The progressive acquisition of somatic driver mutations, copy-number alterations, and epigenetic and transcriptomic changes may enable selected clones to escape functional anergy and become increasingly independent of the original viral stimulus that, in turn, represents an initial trigger of the lymphoproliferative process. Recurrent abnormalities converge on NF-κB, NOTCH, chromatin-regulatory, apoptotic, and cell-cycle pathways, although HCV-associated lymphomas remain molecularly heterogeneous. Emerging microRNA profiles further contribute to the molecular characterization of the transition from chronic infection and cryoglobulinemia to lymphoma. Despite the availability of highly effective antiviral therapies, HCV-associated lymphomagenesis remains clinically relevant and continues to provide an especially informative model for understanding how chronic viral infection can drive human cancer development. Full article

Background/Objectives: Metabolic syndrome (MetS) and low socioeconomic status (SES) are each established drivers of coronary artery disease (CAD), a leading cause of acute cardiovascular presentations to emergency and acute care services. Whether SES modifies the long-term association between MetS and CAD in a universal health coverage setting is unclear. We examined the independent and joint associations of MetS and income-based SES with 20-year incident CAD. Methods: In this nationwide retrospective cohort study using the Korean National Health Insurance Service database, 489,521 adults aged 40–79 years who underwent a national health examination in 2005 and were free of CAD at baseline were followed through 31 December 2024 (up to 20 years). At baseline, the mean age was 54.1 ± 9.2 years, and 252,818 participants (51.6%) were men. MetS was defined by modified harmonized criteria, with body mass index (BMI) ≥ 25 kg/m² substituted for waist circumference. SES was measured by health insurance premium deciles and classified as high (deciles 8–10), middle (4–7), low income (1–3), and Medical Aid (decile 0). The outcome was incident CAD (myocardial infarction or angina pectoris). Multivariable Cox proportional hazards models were adjusted for age, sex, smoking, alcohol consumption, regular exercise, BMI, chronic kidney disease, alternate exposure, and estimated adjusted hazard ratios (aHRs); joint exposure and additive interaction (relative excess risk due to interaction, RERI) were assessed. Results: MetS prevalence was 30.6%. During follow-up, 48,428 participants (9.9%) developed CAD. MetS was independently associated with CAD (aHR 1.84; 95% CI 1.78–1.91), as was a graded socioeconomic gradient (Medical Aid vs. high SES aHR 1.62; 1.54–1.70). Incidence rates ranged from 3.13 (high-SES without MetS) to 11.40 (Medical Aid with MetS) per 1000 person-years. In the joint analysis, Medical Aid beneficiaries with MetS had the highest risk (aHR 2.92; 2.78–3.08 vs. high-SES without MetS; p for interaction < 0.001), with positive additive interaction (RERI 0.68). Conclusions: Over two decades, low SES amplified the CAD burden associated with MetS. Adults living in the most severe material deprivation who also had MetS constituted the highest risk group, of direct relevance to risk stratification and disparities in emergency and acute cardiovascular care. Full article