• Heterologous ORFV-Ad26 vaccination broadens antibody breadth and amplifies cellular immunity against SARS-CoV-2 spike.
    3 weeks ago
    The durability of vaccine-induced immunity is often limited by waning responses, antigenic drift, and anti-vector immunity, highlighting the need for innovative vaccination strategies. Heterologous prime-boost approaches can help overcome these barriers by exploiting the complementary strengths of distinct platforms. Here, we evaluated a replication-deficient Orf virus-based spike vaccine (ORFV-S) in combination with the licensed Ad26 vector vaccine Jcovden (Ad26.COV2.S), using SARS-CoV-2 model. In a clinically aligned intramuscular immunogenicity screen in mice, Jcovden induced strong early anti-spike antibody responses but showed limited boostability, whereas ORFV-S was highly boost-responsive. Mixed regimens outperformed both homologous schedules. ORFV-S prime followed by Jcovden boost elicited the highest spike-binding antibody titers and vigorous CD4+ and CD8+ T-cell responses with a dominant Th1 profile. In the reverse regimen, ORFV-S boost improved inhibition across multiple SARS-CoV-2 variants, including immune-evasive strains and indicated qualitative improvements in the response breadth. Together, these findings suggest that sequence-dependent effects allow heterologous schedules to emphasize either cellular or humoral arms of the adaptive response.
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  • Diagnostic potential of WNT signaling gene methylation in pulmonary tuberculosis.
    3 weeks ago
    The WNT signaling pathway plays important roles in the pathophysiology of pulmonary tuberculosis (PTB). This study aimed to assess the association of the DNA methylation levels of WNT signaling pathway genes and PTB susceptibility, and determine whether the methylation levels might serve as valuable biomarkers for PTB diagnosis.

    We collected blood samples from 98 PTB patients and 96 normal controls, and extracted DNA samples. The methylation levels of promoter region in WNT signaling pathway genes (SFRP1, WNT3A, CTNNB1, WIF-1, DKK-1, LRP5, LRP6) were detected by MethylTarget technique.

    We found that the methylation levels of SFRP1, WNT3A, CTNNB1, DKK-1, LRP6 genes were significantly decreased in the peripheral blood of PTB patients when compared to normal controls, while WIF-1, LRP5 genes methylation levels showed no significant difference between PTB patients and controls. In PTB patients, the increased SFRP1 methylation level was significantly correlated with drug-induced liver injury, pulmonary infection, and the decreased WNT3A, CTNNB1 methylation levels were respectively significantly associated with drug resistance, fever. For diagnosing PTB, the CTNNB1 methylation level demonstrated a relatively higher diagnostic value, achieving an AUC of 0.706. Subsequently, the AUC of WNT3A, DKK-1, LRP6 was 0.660, 0.628, 0.621. The diagnostic value was slightly enhanced when CTNNB1 combined with WNT3A, DKK-1, LRP6, with an AUC of 0.710.

    The methylation levels of SFRP1, WNT3A, CTNNB1, DKK-1, LRP6 genes were significantly decreased in PTB patients, and single gene or multiple genes methylation panels might serve as potential diagnostic biomarkers for PTB.
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  • Global burden of pulmonary arterial hypertension and health inequality in women of childbearing age from 1990 to 2021, with projections up to 2040: the global burden of disease 2021 study.
    3 weeks ago
    To assess the global burden, trends, and inequalities of pulmonary arterial hypertension (PAH) among women of childbearing age (WCBA) from 1990 to 2021, projecting future trends to 2040.

    Using Global Burden of Disease (GBD) 2021 data, we analyzed PAH mortality, incidence, prevalence, and disability-adjusted life years (DALYs) among WCBA aged 15 to 49. Trends were assessed via age-standardized rates (ASR), estimated annual percentage change (EAPC), joinpoint regression, decomposition, and inequality analyses. Future burden was projected using Bayesian age-period-cohort, auto-regressive moving average, and exponential smoothing models.

    The absolute number of PAH cases among WCBA increased globally from 1990 to 2021. Critically, the global age-standardized incidence rate (ASIR) showed a neglected upward trend (EAPC = 0.12), while mortality and DALY rates declined. Significant inequalities were observed, with the ASIR highest in low-middle SDI regions and prevalence highest in high SDI regions. Decomposition analysis identified population growth as the primary driver of increasing burden in low-resource settings. Projections indicate a continued rise in incidence by 2040, alongside declining mortality.

    This study demonstrated a persistent and growing PAH burden among WCBA, marked by significant inequalities. The rising incidence, particularly in low-resource settings, coupled with the cumulative prevalence in high-income regions, underscores an urgent need for targeted public health actions. Region-specific interventions are vital, including integrating PAH screening into maternal health programs in resource-poor settings and optimizing long-term management in high-income countries.
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  • Navigating distrust and competing priorities during the COVID-19 pandemic: insights from Florida to strengthen cooperation.
    3 weeks ago
    Stopping an infectious disease outbreak relies on a coordinated set of actions across public and private institutions and the wider public. However, cooperation with public health recommendations was notably hindered during the pandemic by widespread distrust in science and government and the notion that public health competed with other priorities. This study aims to examine the factors driving distrust and competing priorities in Florida, and potential pathways to overcome these issues.

    We conducted an additional analyses of qualitative data from our original study involving 25 semi-structured interviews with Florida stakeholders from government, academia, and the private sector. We employed a deductive-inductive approach to qualitative content analysis, using themes from the initial study as a guiding framework while allowing for the emergence of additional insights.

    Interviews revealed that inadequate transparency and data availability, politicization, and poor communication were perceived as undermining public trust in science and decision-makers during COVID-19. The economy and individual rights were discussed as priorities competing against public health during the pandemic. Objectives for building trust and balancing priorities included five essential areas: transparency, representation, communication, education, and balance.

    These challenges and objectives reflect the need for a reimagined approach to public health policy and practice-one that is rooted in trust and respect for diverse value systems. By leveraging core collective values that cut across political ideologies, we may mitigate polarization and perceived stigmatization to build a more culturally resonant public health practice.
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  • Psychological wellbeing and social emotional competence of Chinese children and adolescents in the post-pandemic era: patterns, determinants, and interrelations.
    3 weeks ago
    The COVID-19 pandemic has presented distinct challenges to the psychological wellbeing (PWB) and social emotional competence (SEC) of Chinese children and adolescents due to prolonged prevention measures, but knowledge of their PWB and SEC status in the post-pandemic era-including distinctive patterns, essential determinants, and interrelationships-remains limited.

    This study employed a self-report questionnaire with three sections (baseline characteristics, PWB scale, and SEC scale) to survey the PWB and SEC levels of Chinese children and adolescents in Gong'an County, central China. A total of 3,420 participants aged 8-16 from different areas in the district were surveyed and 2,848 valid responses were collected. Additionally, we identified 24 participants with low PWB and SEC scores and conducted follow-up interviews and family visits with them and their parents. Quantitative statistical analyses included descriptive analyses, analysis of variance (ANOVA), logistical regressions, and correlational analyses. Qualitative analyses were conducted to explain the statistical results as well as reveal emerging themed findings.

    The quantitative data revealed moderate PWB and SEC levels among the participants, with significant variations based on baseline characteristics such as grade level, school location, academic rank, parent marital status, household economic condition, and left-behind status. Determinants influencing both PWB and SEC included academic rank, parent marital status, and household economic condition. The interrelationships between PWB and SEC dimensions also highlighted the importance of self-management for the wellbeing of Chinese youths. Furthermore, three theme findings were identified that are aligned with the quantitative results, focusing on PWB and SEC challenges, the impact of economic conditions on family dynamics, and the influence of grade obsession and self-esteem issues in the post-pandemic era.

    Teachers should monitor students' psychological and emotional wellbeing, especially those with poor academic performance, disadvantaged backgrounds, and unstable parental relationships. Non-left-behind children with high social awareness require equal attention. Effective interventions are needed to develop students' self-management and self-awareness, thus promoting their PWB.
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  • The role of telemedicine in the context of the COVID-19 pandemic in Colombia.
    3 weeks ago
    With the onset of the COVID-19 pandemic in Colombia, telemedicine (TM) became a key strategy to sustain healthcare delivery for both acute and chronic conditions. This study aimed to describe the utilization and characteristics of TM during the pandemic in Colombia.

    We conducted a retrospective, descriptive study using administrative and clinical records from a major Colombian health insurance provider covering approximately 15% of the national population. We analyzed all TM consultations between March 2020 and June 2021, assessing sociodemographic, geographic, and clinical characteristics. TM users and the overall insured population were described, and primary care unit (PCU) locations were georeferenced.

    A total of 10,016,931 individuals were enrolled in the health insurance plan, of whom 2,633,564 used TM services during the study period. TM users were predominantly female (62.8%) and aged 19-45 years (55.3%). Most belonged to low-income groups (64.9%) and were affiliated with the subsidized income level group. The most frequent diagnosis was COVID-19 (28.3%), followed by general symptoms and unspecified conditions (19.4%). Telemedicine was used nationwide, with higher concentrations in central and northern departments such as Antioquia and Bogotá.

    During the pandemic, telemedicine was widely adopted across Colombia and reached large segments of low-income populations, suggesting its potential to support healthcare access in diverse settings. While our descriptive design does not allow for causal claims about effectiveness or equity, these findings highlight the value of TM as a complementary healthcare delivery model. Continued investment in digital infrastructure, workforce training, and primary care networks will be essential for its long-term integration into Colombia's health system.
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  • Surgical and Endovascular Management of Aortic Thrombosis in COVID-19 and Vaccine-Induced Immune Thrombotic Thrombocytopenia.
    3 weeks ago
    COVID-19 has been associated with a hypercoagulable state, leading to various thrombotic complications, including aortic thrombosis, a rare but severe manifestation requiring surgical intervention. Additionally, vaccine-induced immune thrombotic thrombocytopenia (VITT), linked to adenoviral vector vaccines, presents unique surgical challenges due to a heightened risk of thrombosis and bleeding. This review focuses on the surgical management of COVID-19-associated aortic thrombosis and VITT-related large-vessel occlusions.

    Surgical intervention in COVID-19-associated aortic thrombosis depends on thrombus burden, patient stability, and associated comorbidities. Open thrombectomy, aortic bypass, and hybrid endovascular techniques have been employed, with perioperative anticoagulation being critical to prevent recurrence. High thrombus burden cases often require open repair, while endovascular approaches are preferred in high-risk patients. Mortality rates remain elevated (up to 30%), with post-surgical complications including recurrent thrombosis and limb loss. In VITT cases, surgical revascularization is complicated by thrombocytopenia and a prothrombotic state, necessitating non-heparin anticoagulation and close hematologic monitoring. Delayed diagnosis and inappropriate anticoagulation significantly worsen outcomes.

    The surgical management of aortic thrombosis in COVID-19 and VITT patients requires a multidisciplinary approach, incorporating vascular surgery, hematology, and intensive care. Early intervention with individualized surgical and anticoagulation strategies is crucial in optimizing outcomes. Further research is needed to refine surgical decision-making, improve postoperative anticoagulation protocols, and enhance patient survival in these complex thrombotic conditions.
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  • EFFICACY OF NASAL IRRIGATION WITH ISOTONIC AND HYPERTONIC SOLUTIONS AFTER ENDOSCOPIC SINUS SURGERY FOR CHRONIC RHINOSINUSITIS WITH NASAL POLYPOSIS.
    3 weeks ago
    Endoscopic sinus surgery (ESS) is often involved in the treatment of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Nasal irrigation after ESS is recommended to improve healing and nasal symptoms in these patients. This study compared the efficacy of nasal irrigation with either an isotonic solution of 0.9% NaCl or a hypertonic solution of 2.3% NaCl comprising algal extracts. This was a randomized cohort study that included patients with CRSwNP after ESS who used isotonic solution and hypertonic 2.3% solution enriched with algal extracts (Undaria pinnatifida and Spir- ulina platensis). Patients filled out the total nasal symptom score (TNSS) questionnaire on visual analog scale of five symptoms, i.e., nasal obstruction, nasal secretion and/or postnasal discharge, sense of pressure in the face, headache, loss of the sense of smell preoperatively, and on postoperative days 7 and 14. Endo- scopic Lund-Kennedy (LK) score was also recorded. The study included 54 patients with CRSwNP that had undergone ESS, mean age 49.5 years. There were 53.7% of male patients. Thirty (55.56%) patients had other comorbidities such as allergic rhinitis, allergy to food, or/and asthma. Five (9.25%) patients had CRSwNP, asthma and allergy to nonsteroidal anti-inflammatory drugs. TNSS improved after 7 and 14 days in both groups; greater improvement of TNSS and LK score was observed in the group of patients that used hypertonic solution with algae, but it did not reach statistical significance. Improvement in particular symptoms was also recorded in the hypertonic solution group both on postoperative days 7 and 14, especially of sneezing and itching. The results of this study confirmed therapeutic benefits of nasal ir- rigation in CRSwNP patients following ESS. Patients who used hypertonic solution enriched with algae experienced greater improvement in sneezing and itching over the 14-day period.
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  • FACTORS ASSOCIATED WITH COVID-19 RELATED DEATH IN 2020 IN CROATIA: A NATIONWIDE OBSERVATIONAL COHORT STUDY.
    3 weeks ago
    The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has had a global effect on mortality. Many attempts were made to identify those at the highest risk of death if infected with SARS-CoV-2, yet the relative importance and global generalizability of individual risk factors remain unclear. At the Croatian Institute of Public Health, electronic health data from multiple databases were combined to examine factors associated with COVID-19 related death. Data on 212 615 patients confir med to have COVID-19 by a positive RT-PCR in 2020 were pseudonymously linked to hospital records and 16 150 hospitalized patients were identified. Apart from older age and male sex, major factors associated with an increased rate of mortality among patients hospitalized with COVID-19 were cardiovascular diseases (adjusted HR: 1.20; 95% CI 1.12-1.28); diabetes (adjusted HR: 1.17; 95% CI 1.09-1.25); and chronic lower respiratory diseases (adjusted HR: 1.10; 95% CI 1.02-1.18). This Croatian study used primary care and hospital data to establish factors associated with COVID-19 related death among patients hospitalized with COVID-19. The results of this study provide rigorous evaluation of the previously defined risk factors and offer guidance for further studies that will create prognostic models based on empirical data from 2020.
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  • TELEDERMATOLOGY AS A TRIAGE METHOD DURING THE COVID-19 PANDEMIC AND EARTHQUAKE AFTERMATH IN ZAGREB.
    3 weeks ago
    The COVID-19 pandemic has put a tremendous burden on the medical community and brought a great number of accompanying issues, as well as other closely associated diseases. The response to this public health and medical challenge was outstanding. However, dealing with the COVID-19 pandemic and various issues brought on by the earthquake was successfully facilitated by the use of teledermatology. This innovative technology enabled dermatovenereologists to stay in continuous touch with their patients and provide much needed care and assistance in difficult circumstances caused by several crises.
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