Search Results (11,570)

Influenza A viruses constantly threaten the global population, with seasonal outbreaks occurring in different parts of the world, including avian influenza. Severe influenza A virus infections are strongly associated with the cytokine storm, which can contribute significantly to morbidity and even mortality. The virulence and high mutability of these viruses necessitate more effective treatment strategies and regimens to manage patients, especially those with a severe disease. Favipiravir is an antiviral agent approved in Japan for treating influenza virus strains resistant to the current antivirals. The objective of this study is to investigate the combination treatment of Favipiravir paired with selected repurposed drugs to determine the effectiveness of these combinations against influenza A virus replication as well as their effects on cytokine expression. Specific combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin were identified to be highly synergistic and effective in inhibiting live virus titers of an influenza H3N2 clinical strain by 4 log₁₀. Furthermore, combinations of Favipiravir with Doxycycline or Azithromycin also exhibited immunomodulatory effects on pro-inflammatory cytokines by strongly reducing the relative mRNA expression of IFN-γ, IL-6, TNF-α and IL-1β. Notably, monotherapy with Andrographolide also completely inhibited influenza virus titers by 4 log₁₀. Specific combinations of Favipiravir with Artesunate or Andrographolide revealed additive effects by inhibiting influenza virus titers by about 2 or 1.5 log₁₀, respectively. Our findings indicate that specific drug combinations show promising efficacy and potential in the treatment of influenza and warrant further studies using influenza models of human cell, tissue and animal infection. Full article

Background/Objectives: Perioperative neurocognitive disorders (PNDs), including delirium and postoperative cognitive dysfunction, affect 10–50% of elderly surgical patients and are associated with increased morbidity and mortality, as well as substantial healthcare costs. Despite their clinical significance, the underlying mechanisms remain incompletely understood and effective interventions are limited. This narrative review synthesizes current evidence on the pathophysiology, risk factors, and management strategies for PNDs. Methods: We conducted a comprehensive literature review of peer-reviewed publications addressing PND epidemiology, mechanisms, assessment, and interventions. Key databases were searched for studies published through 2025, with emphasis on systematic reviews, meta-analyses, and landmark clinical trials. Results: PND represents a spectrum of cognitive impairments with multifactorial etiology involving neuroinflammation, neurotransmitter imbalances, and blood–brain barrier dysfunction. Advanced age, pre-existing cognitive impairment, and surgical factors constitute major risk domains. Validated assessment tools including the Confusion Assessment Method (CAM) and 4AT enable systematic detection. Multicomponent non-pharmacological interventions demonstrate 30–40% delirium reduction, while pharmacological prevention shows limited efficacy. Emerging evidence links perioperative delirium to accelerated long-term cognitive decline and increased dementia risk. Conclusions: PND represents a significant public health challenge requiring systematic attention in aging surgical populations. Evidence-based multicomponent interventions should be integrated into routine perioperative care pathways. Future research must elucidate mechanistic pathways linking acute delirium to chronic cognitive impairment and develop targeted therapies to preserve cognitive health in surgical populations. Full article

Respiratory infections cause substantial morbidity and mortality in older adults and other at-risk adult populations. Despite the availability of effective vaccines, adult vaccination coverage remains suboptimal. This narrative review examines strategies designed to improve vaccine uptake among non-pregnant adults aged ≥18 years and inform future adult vaccination strategies. We conducted a targeted literature search using keywords for vaccination, respiratory diseases, strategy/program/implementation, and adults in PubMed database and CDC, WHO, and ECDC websites, between 2014 and 2024. A snowball search of literature reviews and key references was also performed to identify additional relevant studies. Eligible publications focused on vaccination strategies against influenza, COVID-19, and pneumococcal disease targeting non-pregnant adults (≥18 years). We categorized the strategies by intervention type to describe their influence on vaccination campaigns and vaccine uptake/coverage. We included 45 publications, encompassing strategies focused on individual decision-making, healthcare system functions, and national policy. Educational and awareness interventions (such as healthcare worker/provider recommendations during consultation, phone calls, letters, text messages, and social media outreach) reportedly raised vaccination rates. Access-related factors, including convenient vaccination sites and free or subsidized vaccines, were reported to be important factors in improving coverage in underserved communities. Within healthcare settings, strategies such as continuous vaccine provider training and workflow/process optimization were shown to enhance vaccination delivery. At the local or national policy levels, legislation governing program targets shaped immunization efforts and facilitated collaborations and partnerships to expand campaign reach. The findings may inform policymakers and public health/immunization practitioners in designing context-specific immunization initiatives that effectively reach adult populations. Full article

Introduction: Minimally invasive pancreatoduodenectomy (MIPD), including laparoscopic (LPD) and robotic approaches (RPD), has gained increasing attention as an alternative to open pancreatoduodenectomy (OPD). Despite rapid technological progress, concerns persist regarding safety, reproducibility, and oncological adequacy. The publication of randomized controlled trials (RCTs) provides essential high-level evidence to reassess the true benefits and limitations of MIPD. Methods: This narrative review synthesizes all available RCTs comparing LPD and RPD with OPD. Major domains evaluated include mortality, major morbidity, intraoperative parameters, postoperative recovery, oncological outcomes, conversion, costs, and the influence of surgeon experience and institutional volume. The objective is to contextualize RCT findings rather than perform a quantitative meta-analysis. Discussion: Across studies, LPD demonstrates comparable mortality and complication rates to OPD in high-volume centers, with consistent reductions intraoperative blood loss (IBL) and shorter recovery or length of stay (LOS). RPD shows more heterogeneous results: one large trial reported improved postoperative recovery, whereas the EUROPA trial identified higher rates of pancreatic fistula (POPF) and delayed gastric emptying (DGE) alongside significantly increased costs. Both LPD and RPD achieve oncological outcomes equivalent to OPD, and 3-year survival data confirm the long-term non-inferiority of LPD. However, operative time remains longer for all minimally invasive approaches, and conversion persists as a marker of technical difficulty and incomplete learning curve. Conclusions: Current RCT evidence indicates that MIPD is safe, feasible, and oncologically sound only when performed by surgeons who have surpassed the demanding learning curve within specialized, high-volume centers. The benefits, mainly reduced IBL and faster recovery, must be weighed against longer operative times, conversion risks, and substantially higher costs for RPD. MIPD should therefore be considered an advanced option rather than a universal standard, and its broader implementation requires structured training pathways, appropriate patient selection, and institutional readiness. Full article

Driven by rapid socioeconomic progress and changing lifestyles, the global burden of cardiovascular diseases (CVDs) continues to escalate, with surging morbidity and mortality rates imposing a severe threat to public health. Clinical treatments are focused on the alleviation of treatments, highlighting the need for a deeper understanding of CVDs pathogenesis and the development of targeted therapies. Recent studies have identified imbalances in intracellular Ca²⁺ homeostasis as a key pathological mechanism in the progression of CVDs. Notably, sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), a membrane protein encoded by the ATP2A2 gene and ranging from 97 to 115 kDa in molecular weight, plays a pivotal role in regulating intracellular Ca²⁺ levels. Extensive evidence links abnormal SERCA2 function to various CVDs, including heart failure, cardiac hypertrophy, atherosclerosis, and diabetic cardiomyopathy. This review systematically explores the regulatory mechanisms of SERCA2 expression and its functional regulation—including transcriptional regulation, post-translational modifications, and protein–protein interactions—and further investigates its pathological roles in cardiovascular diseases as well as its potential as a therapeutic target. By synthesizing current knowledge, this article aims to provide new insights for future basic research and establish a theoretical foundation for clinical applications. Full article

Cardiovascular health and depression influence each other bidirectionally and negatively, leading to high comorbidity rates, and favouring higher morbidity and mortality. Heart rate variability (HRV) has received much attention as a “biomarker” for major depressive disorder, with studies suggesting its potential both as a diagnostic and as a predictive biomarker. This narrative review offers a first orientation to the evidence base for researchers entering the field. We present and discuss the state-of-the-art evidence of cross-sectional and longitudinal studies (including observational, pharmacological interventions, and non-pharmacological interventions) linking depression and/or depressive symptoms to HRV by highlighting meta-analyses and key studies in the field. We briefly discuss the physiological context for interpretation of HRV and important confounders to consider, including the influence of genetics, age, sex, antidepressant medication, and lifestyle factors. Finally, with this information at hand, we discuss and provide guidance for factors to consider when using HRV in designing a study. Our literature review indicates that while there is potential for vagally mediated HRV to be of value in predicting future depression, more in-depth and stratified research of HRV is beneficial to the field and the understanding of what HRV can mean for depression research. Full article

Background/Objectives: Unequal access to cervical cancer screening and treatment remains a significant contributor to preventable morbidity and mortality for women in the Amazon Basin, compounded by geographic, social and infrastructural barriers. Given the fragmented nature of the existing evidence, this systematic review aims to synthesize available findings on barriers to cervical cancer screening and treatment for this region. The implications of these findings are examined to inform the development of actionable strategies to improve equity in prevention and care. Methods: This systematic review was conducted in accordance with PRISMA 2020. Searches were conducted on November 7, 2025, in PubMed/MEDLINE, Web of Science, and SciELO, utilizing combinations of MeSH terms, keywords, and free-text expressions. Studies were considered eligible if they addressed barriers to cervical cancer screening or treatment among women living in the Amazon Region. Two reviewers independently screened the studies and extracted the relevant data. The risk of bias was assessed using the JBI checklists, the Newcastle–Ottawa Scale, and the MMAT. A narrative synthesis summarized the results. Results: Of 57 studies identified, 11 were included. Organizational and health-system barriers were reported most frequently, including scheduling difficulties, long wait times, a shortage of professionals, and equipment unavailability. Socioeconomic barriers were most often related to younger age, low income, limited schooling, and care related expenses. Cultural factors were frequently linked to fear of the procedure and insufficient knowledge about cervical cancer. Geographic barriers included rural residence and travel difficulties. Conclusions: This systematic review indicates that disparities in cervical cancer screening in the Amazon region are primarily associated with organizational and health-system-related barriers, together with socioeconomic, cultural, and geographic factors. These findings highlight the need for equitable, multisectoral interventions to strengthen service organization, improve health literacy, and expand timely access to screening and treatment for underserved women. Full article

Flaviviruses are responsible for significant morbidity and mortality worldwide. Despite intensive research, the structure and oligomerization properties of non-structural (NS) proteins, like NS2 or NS4, are still uncertain because of their high hydrophobicity. Solution NMR has shown that NS2B protein has two hydrophobic domains, organized as two short α-helical hairpins that contribute to both viral RNA replication and particle formation. These are separated by a hydrophilic loop that is a cofactor of protease NS3. However, the oligomerization behavior of NS2B has not been explored in detail. Herein, we have expressed Zika virus NS2B protein (ZIKV NS2B) and characterized its oligomerization in both detergent and lipids using crosslinking in liposomes, and mass photometry and analytical ultracentrifugation in detergent. We show that, in contrast to the small oligomers proposed earlier, ZIKV NS2B protein has a very complex oligomerization behavior, forming from dimers to very large multimers (>10) in both detergent and lipids. Although AlphaFold (AF) provided a model for monomeric NS2B that is consistent with available experimental data, no oligomeric model was predicted with confidence. We suggest that the role of the two short α-helical hairpins in membrane destabilization and reshaping host ER during viral infection may be aided or triggered by multimerization. Finally, although our results report a high tendency of NS2B to oligomerize, in the context of the infected cell, a biologically relevant multimeric complex may necessitate other viral proteins like NS4A or NS4B and/or host proteins. Full article

Off-pump coronary artery bypass grafting (OPCAB) represents one of the most significant technical innovations in contemporary cardiac surgery. Developed as an alternative to conventional on-pump coronary artery bypass grafting (ONCAB), OPCAB avoids cardiopulmonary bypass and its associated systemic inflammatory response, aiming to reduce perioperative morbidity and improve recovery. Over the past three decades, advances in stabilization devices, intracoronary shunts, anesthetic management, and surgical training have refined the procedure, making it safer and more reproducible. Despite these developments, OPCAB adoption remains inconsistent worldwide, reflecting ongoing debate about its relative benefits and limitations. Evidence from randomized controlled trials, meta-analyses, and large registries suggests that OPCAB achieves comparable early mortality to ONCAB, with potential advantages in reducing renal dysfunction, neurocognitive decline, and perioperative bleeding. These benefits appear most pronounced in high-risk subgroups, including elderly patients and those with significant comorbidities. However, concerns persist regarding long-term graft patency, completeness of revascularization, and variability in outcomes depending on surgeon experience and institutional expertise. Cost-effectiveness analyses have suggested potential resource savings, but these are offset by training requirements and the technical complexity of the procedure. Global practice variation highlights the influence of surgical culture, guideline ambiguity, and institutional resources. Barriers to universal adoption include technical challenges, inconsistent long-term outcomes, and limited exposure in training programs. In the future, robotic and minimally invasive OPCAB, as well as hybrid revascularization strategies, may expand its role. This review synthesizes current evidence, explores barriers to widespread implementation, and outlines future directions for integrating OPCAB into balanced, evidence-based clinical practice. Full article

Background/Objectives: Staphylococcus aureus bloodstream infections (SABSIs) are associated with significant morbidity and mortality and are often complicated by infective endocarditis (IE). During the COVID-19 pandemic, fewer transesophageal echocardiographs (TEEs) were performed for patients diagnosed with SABSI, and this study examined the impact on clinical outcomes associated with this change in practice. Methods: This retrospective observational study included adult patients treated for SABSI who were admitted pre-COVID-19 (1 March 2018 to 11 March 2020) and during COVID-19 (12 March 2020 to 1 March 2022). Primary outcomes were rates of confirmed IE and duration of antibiotic therapy (DOT). Results: Of 333 screened patients, 214 were included (107 per group). Patients in the COVID-19 group were older (51.49 vs. 56.31 years, p = 0.013); other baseline characteristics were similar. Catheter-related infections were the most common source in the pre-COVID-19 and COVID-19 groups (30.8% vs. 18.9%, p = 0.089). Rates of TEE procedures significantly declined during COVID-19 (72% vs. 50.9%, p = 0.002); rate of confirmed IE (9.4% vs. 12.1%; p = 0.660) and median DOT (28 vs. 28 days; p = 0.596) were similar. Ninety-day mortality was higher in the COVID-19 group (10.4% vs. 22.2%, p = 0.019); other outcomes were not statistically different. Conclusions: The COVID-19 pandemic led to a notable decline in TEEs performed for SABSI, but the majority of clinical outcomes were unchanged. Mortality was significantly higher in the COVID-19 group, but it is uncertain that this was solely due to the change in practices. In a healthcare system that universally recommends TEE, scoring systems may help identify which patients are highest priority for TEE versus those that could undergo a transthoracic echocardiogram. Full article

Malignancy-related gastrointestinal bleeding (GIB) remains a significant clinical challenge, contributing substantially to morbidity, mortality, and healthcare utilization in patients with cancer. Up to 10% of individuals with advanced malignancies develop GIB during their disease, and these episodes are frequently characterized by a high risk of rebleeding and poor long-term hemostatic control. Tumor-associated bleeding typically arises from friable, infiltrative, and highly vascular lesions that respond suboptimally to conventional endoscopic techniques such as thermal coagulation or mechanical clipping. These limitations underscore the need for improved diagnostic accuracy and more reliable therapeutic options. Recent advances in imaging modalities, including contrast-enhanced CT studies, have enhanced the ability to localize and characterize bleeding sources in complex oncologic cases. Parallel developments in endoscopic hemostasis—such as over-the-scope clips and contact-free coagulation devices—have expanded the therapeutic armamentarium for managing malignant bleeding. Clinically, topical hemostatic powders—particularly TC-325—represent a highly effective option for achieving rapid endoscopic hemostasis, supported by the strongest comparative evidence and the highest rates of immediate bleeding control among currently available technologies. In this review, we synthesize contemporary diagnostic approaches to GIB and place particular emphasis on the evolving and emerging therapeutic strategies for malignancy-related bleeding. We also highlight innovative technologies that are reshaping clinical practice and improving management options in this challenging clinical domain. Full article

Disorders of thrombosis and bleeding contribute to a significant morbidity and mortality burden worldwide. Correctly identifying contributing factors towards either thrombosis or bleeding carries implications for diagnosis, prognosis and management. Although there are established and commonly used biomarkers for both circumstances, the complexity of hemostasis contributes to the wide variability in assay methodology and information provided by each individual assay. There are several emerging biomarkers of thrombosis and hemostasis, which require further evaluation of their roles in diagnosis and management in specific patient populations. This narrative review summarizes established, emerging, and exploratory biomarkers of both thrombosis and bleeding disorders, outlining their biological roles, diagnostic utility, and limitations, with a particular focus on clinical relevance, assay methodology and future directions. Full article

Type 2 diabetes mellitus (T2DM) is a major metabolic disorder characterized by chronic hyperglycemia with far-reaching morbidities. Among these, diabetes-related cerebrovascular complications such as ischemic and hemorrhagic stroke, cerebral blood vessel disease, and vascular dementia are significant contributors to morbidity and mortality. Adipose tissue is a metabolically active endocrine organ that becomes dysfunctional in T2DM and communicates with distant tissues via secreted factors, including extracellular vesicles such as exosomes (EXs), phospholipid bilayer-enclosed nanosized particles. These adipocyte-derived exosomes (Ad-EXs) carry bioactive cargo, including lipids, proteins, and microRNAs that influence the function of distant organs, including the brain. Evidence indicates that Ad-EXs in T2DM are a significant risk factor for cerebrovascular complications via neurovascular impairment either directly through the adipose tissue–brain axis or indirectly by other organs. This review provides an overview of current knowledge on how Ad-EXs from different adipocyte populations contribute to cerebrovascular complications through oxidative stress, blood–brain barrier disruption, neuroinflammation, and mitochondrial dysfunction. Particular emphasis is placed on recent findings and gaps in knowledge linking diabetic Ad-EXs with brain microvascular endothelial cells that mediate neurovascular crosstalk, contributing to stroke susceptibility and cognitive decline. We also discuss the potential of Ad-EXs as biomarkers and therapeutic targets for cerebrovascular complications of T2DM. Full article

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial morbidity and mortality due to increased risks of stroke, heart failure, and death. Catheter ablation is now firmly established as a first-line or early rhythm control strategy in selected patients with paroxysmal AF and as a Class I indication in symptomatic patients with persistent AF refractory to antiarrhythmic drug therapy. However, outcomes remain more variable in persistent and long-standing persistent AF, reflecting greater atrial substrate complexity, procedural challenges, and ongoing uncertainty regarding optimal ablation strategies. This review provides a structured, evidence-based overview of contemporary catheter ablation approaches for AF, with particular emphasis on persistent disease. We discuss the anatomical and mechanistic rationale underlying pulmonary vein isolation and adjunctive lesion sets, summarize current clinical evidence supporting various strategies, and highlight differences in efficacy, safety, and reproducibility. In addition, we address the importance of patient selection, shared decision making, procedural expertise, and comprehensive risk factor modification as integral components of successful long-term rhythm control. By integrating guideline recommendations with mechanistic insights and clinical trial data, this review aims to clarify the current best practices and identify remaining knowledge gaps in the catheter ablation of atrial fibrillation. Full article