Search Results (1,249)

Background: The end of the COVID-19 public health emergency of international concern (PHEIC) in May 2023 marked a transition from disruption to recovery and rebuilding of health systems. The WHO African Region entered this period with declining routine immunization coverage, widening inequities, and fragile surveillance systems. We conducted a critical narrative synthesis of post-PHEIC recovery and the transformation of immunization systems in the region from 2023 to 2025. Methods: We thematically analyzed publicly available data from the WHO and other sources using a systems-oriented framework covering immunization coverage, equity, vaccine introductions, disease control, governance, financing, and data systems. Results: Regional coverage for most antigens was restored to 2019 pre-pandemic levels by 2024, e.g., three doses of diphtheria-tetanus-pertussis-containing vaccines at 76%. However, progress remains insufficient to meet the Immunization Agenda 2030 (IA2030) target of 90% coverage. In addition, there were 6.7 million zero-dose children in the 2024 birth cohort (6.3% higher than the 6.3 million in 2019), concentrated in a few countries. The IA2030 target is a 50% reduction in the number of zero-dose children by 2030, compared to 2019. Recovery initiatives have restored services, while accelerated introductions (e.g., malaria vaccines introduced in 20 new countries in 2024–2025) signal renewed system momentum. Yet, progress has plateaued at pre-pandemic levels, reflecting structural constraints rather than sustained transformation. Concurrently, recurrent outbreaks of measles, yellow fever, and other vaccine-preventable diseases highlight persistent immunity gaps and surveillance limitations. Structural constraints (including financing fragility, subnational inequities, and system fragmentation) continue to limit sustained progress. Conclusion: This study offers important insights that can inform immunization policymaking in the WHO African Region and beyond. Current post-PHEIC trends reflect recovery without transformation. Achieving IA2030 targets will require a shift from broad coverage expansion to precision delivery approaches that prioritize zero-dose and underserved populations. Immunization must be positioned as a central pillar of primary health care and health security systems. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Clear cell renal cell carcinoma (ccRCC) is characterized by marked biological heterogeneity, which limits the prognostic accuracy of conventional clinicopathological models. Increasing attention has therefore focused on identification of biomarkers that can enhance risk stratification throughout all stages of the disease. Starting from the current state of the art, this narrative review summarizes and critically appraises the evidence published over the past decade regarding prognostic biomarkers in ccRCC. The analysis is structured into four overarching domains: (i) genomic biomarkers, covering somatic alterations and transcriptomic signatures; (ii) tissue-based biomarkers, including immunohistochemical surrogates and immune microenvironment features; (iii) circulating biomarkers, such as systemic inflammation parameters and indices; and (iv) integrated predictive models, represented by emerging multi-omic approaches. Going through the broad framework of potential prognostic biomarkers, emphasis is placed on their individual and integrative value in relation to classic clinical-pathological factors and survival parameters. At the tissue level, chromosome 3p-related alterations constitute a central molecular feature of ccRCC. Among these, BAP1 loss has emerged as one of the most consistently validated indicators of aggressive tumor behavior. Disruption of the SETD2/H3K36me3 axis and immune-related biomarkers, including PD-L1 expression, have demonstrated prognostic associations in selected settings, although with variable and context-dependent performance. In the circulating compartment, plasma KIM-1 has shown prognostic relevance following nephrectomy, while postoperative detection of circulating tumor DNA (ctDNA) may identify patients at increased risk of recurrence. However, limited analytical sensitivity and methodological heterogeneity currently restrict the broader clinical applicability of ctDNA-based strategies. Systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio, show reproducible associations with outcomes but largely reflect host inflammatory status rather than tumor-specific biology. However, no single biomarker currently supports routine prognostic implementation in ccRCC. Future progress will likely depend on integrative models combining genomic, tissue-based, immune, and circulating parameters with established clinical variables. Prospective validation and clear demonstration of incremental clinical utility will be essential before such strategies can meaningfully inform therapeutic decision-making. Full article

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

The skin–brain axis constitutes a complex, bidirectional network integrating cutaneous sensory, immune, and neuroendocrine systems with central neural circuits involved in emotion regulation, stress responsivity, and social cognition. Advances in psychodermatology and cosmetic science have progressively extended this framework to the emerging field of neurocosmetics, which explores how topical formulations, sensorial properties, and cutaneous neuromodulators may influence psychological well-being, affective states, and perceived stress. The aim of this narrative review is to synthesize current evidence on the biological foundations of the skin–brain axis and to critically examine the implications of these mechanisms for neurocosmetic interventions from a psychological and psychiatric perspective. It describes the biological substrates underlying skin–brain communication, including the cutaneous hypothalamic–pituitary–adrenal axis, neuropeptides, neurotrophins, transient receptor potential channels, and endocannabinoid signaling, and examines how these pathways are targeted by neurocosmetic interventions. Particular attention is devoted to neuroactive compounds, such as peptides, cannabinoids, botanicals, and aromatherapeutic molecules, as well as to sensorial strategies involving texture, temperature, and olfactory cues, which may modulate mood, anxiety, and self-perception through peripheral mechanisms. From a psychological and psychiatric perspective, the review discusses the intersection between stress-related skin conditions, body image disturbances, and emotional dysregulation, highlighting how cosmetic practices may influence subjective well-being beyond purely aesthetic outcomes. Methodological limitations of the existing literature, including the heterogeneity of study designs and outcome measures, as well as ethical considerations related to mood- and stress-related claims in cosmetic products, are critically examined. Finally, future research directions are outlined, and a translational framework is proposed to integrate dermatology, neuroscience, and mental health within next-generation cosmetic science. Full article

Background/Objectives: Hepatic diseases frequently present with ocular manifestations that aid diagnosis, provide prognostic data, and guide therapy. Despite the clear utility of the liver–eye axis, the literature lacks reviews that categorize these manifestations by etiology. This review evaluates current evidence to identify ocular findings that serve as clinical tools for diagnosis, prognosis, and therapeutic monitoring of hepatic pathologies. Methods: A narrative review was conducted using PubMed and Google Scholar to identify English-language articles addressing ocular manifestations associated with liver disease. The primary search encompassed publications from 2000 to 2025, with inclusion of select foundational works published prior to 2000 when they represented seminal studies establishing diagnostic criteria, pathophysiological mechanisms, or natural history data not superseded by subsequent research. Search terms included combinations of liver, hepatic, hepatitis, cirrhosis, cholestasis, eye, ocular, retina, cornea, sclera, conjunctiva, ophthalmic manifestations, and specific disease names. All study designs were eligible. Society guidelines, systematic reviews, and studies from high-impact journals were prioritized. The final selection comprised 59 references representing the most authoritative sources across the spectrum of hepatic conditions. Results: A spectrum of ocular findings linked to distinct hepatic conditions was identified. Manifestations with established clinicopathologic associations were categorized into congenital and acquired etiologies. Congenital liver pathologies included metabolic disorders (Wilson disease, galactosemia, lysosomal storage disorders) and syndromic/genetic causes (Alagille syndrome, hereditary hemochromatosis). Acquired liver diseases encompassed infectious (hepatitis B/C), drug-induced and iatrogenic (interferon, immune checkpoint inhibitors), nutritional (vitamin A deficiency), neoplastic (metastatic hepatocellular carcinoma), and cirrhotic causes. Conclusions: Specific ocular signs raise clinical suspicion for underlying liver disease and warrant targeted hepatic evaluation. Recognizing these associations facilitates earlier diagnosis and improves outcomes. Systematic screening for these signs is supported in at-risk populations, and prospective validation studies should establish their sensitivity and specificity. Full article

Background: Cigarette smoking exposes the human body to a complex mixture of toxic and carcinogenic compounds that can exert widespread biological effects across different organ systems. From addictive responses and consequence maladaptive neuroendocrine responses, cigarette smoke delivers a variety of reactive oxygen species, polycyclic aromatic hydrocarbons, nitrosamines, and heavy metals that collectively contribute to oxidative stress, inflammation, endothelial dysfunction, and metabolic disruption. The liver, as the primary organ responsible for xenobiotic metabolism, plays a central role in processing these harmful substances and is therefore uniquely susceptible to their effects. This narrative review will aim to provide an overview of the current evidence of cigarette smoking effects on hepatic structure and function and discuss clinical implications. Methods: This narrative review synthesizes evidence from in vitro studies, animal models, and human clinical research examining the effects of cigarette smoking on liver biology. Mechanistic pathways of injury, metabolic and vascular alterations, and clinical consequences for liver disease were considered. Results: Smoking influences hepatic function both directly—through biotransformation pathways generating reactive intermediates—and indirectly via vascular impairment, immune modulation, hormonal alterations, and changes in lipid and glucose metabolism. Emerging evidence indicates that cigarette smoking contributes to hepatic steatosis, accelerates fibrosis progression, worsens outcomes in viral and alcohol-related liver disease, and increases the risk of hepatocellular carcinoma. Conclusions: Cigarette smoking exerts multifaceted deleterious effects on the liver. Recognition of smoking as a modifiable risk factor for liver-related morbidity underscores the importance of smoking cessation in patients with or at risk for liver disease and highlights implications for research and clinical practice. Full article

Allergic asthma is a prevalent chronic inflammatory disease of the airways whose pathogenesis has traditionally been attributed to localized immune dysfunction within the lung. However, accumulating evidence from microbiome research supports a broader system-level perspective in which cross-organ interactions contribute to disease susceptibility and progression. In particular, the gut–lung axis has emerged as a key regulatory pathway linking intestinal microbial ecology, immune development, and respiratory health. This review synthesizes current epidemiological, mechanistic, and experimental evidence supporting the role of gut microbiota dysbiosis in allergic asthma. We examine how early-life environmental and nutritional exposures and gut microbiota establishment during critical developmental windows shape long-term immune tolerance and asthma susceptibility. We then summarize characteristic features of asthma-associated gut dysbiosis and discuss how microbial-derived metabolites, including short-chain fatty acids, tryptophan metabolites, pro-allergic lipid mediators such as 12,13-dihydroxy-9Z-octadecenoic acid, and bacterial-derived histamine, modulate distal airway immune responses through epigenetic, receptor-mediated, and immune trafficking mechanisms. Particular emphasis is placed on the role of diet as a key upstream regulator of gut microbiota composition and metabolic function. Finally, we evaluate experimental and translational studies targeting the gut–lung axis, including dietary modulation, microbiome-targeted interventions such as fecal microbiota transplantation, and emerging postbiotic approaches. Collectively, current evidence indicates that gut microbial composition and metabolic function are critical determinants of respiratory immune homeostasis. Targeting the gut–lung axis through nutrition- and microbiome-based strategies offers a promising avenue for the prevention and precision treatment of allergic asthma. Full article

Galectin-3 (Gal-3) is a multifunctional molecule that exerts pleiotropic effects in inflammatory responses and contributes to the pathogenesis of numerous immune-mediated diseases. Although Gal-3 has been known for more than five decades, it remains a lectin with intriguing and not yet fully elucidated properties. The existing body of evidence underscores the importance of Gal-3 in the regulation of homeostatic and inflammatory processes. Neurotrophins are traditionally recognized as key regulators of neuronal development, survival, and synaptic plasticity; nevertheless, accumulating evidence indicates that they also play important roles in immune regulation and neuroimmune communication. Importantly, neurotrophins are also produced by immune cells, including monocytes, macrophages, lymphocytes, and basophils, which express functional neurotrophin receptors including tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase A (TrkB), and p75 neurotrophin receptor (p75NTR). In this narrative review, we synthesize current evidence on neuroinflammation, neurotrophins, and Gal-3, with a particular focus on the molecular mechanisms involved in the crosstalk between neurotrophins and Gal-3 or immune cells. We further examine how this neuroimmune–neurotrophic crosstalk contributes to the pathogenesis of psychiatric and neurodegenerative disorders, as well as other neurological conditions. Finally, we discuss the emerging therapeutic potential of targeting neurotrophins and Gal-3 as modulators of neuroinflammation. Full article

Background/Objectives: Peritoneal metastasis represents the most frequent and prognostically unfavorable metastatic pattern in gastric cancer, largely due to limited sensitivity of conventional imaging, delayed diagnosis, and insufficient response assessment. The aim of this review is to provide an overview of the current evidence on the diagnosis and treatment of gastric cancer with peritoneal metastases and to address current treatment limitations and options. Methods: This review was designed as a narrative review and is based on an extensive literature search in established databases. Results: Systemic chemotherapy remains the cornerstone of palliative treatment, improving the survival and quality of life compared with the best supportive care; however, outcomes in peritoneally metastatic disease remain poor. Advances in molecularly targeted and immune-based therapies have extended survival in selected patient populations, yet favorable molecular profiles are mainly unknown in peritoneal metastases. Staging laparoscopy and semi-quantitative assessment using the Peritoneal Cancer Index (PCI) are therefore essential for accurate diagnosis, prognostication, and treatment selection. Growing evidence from retrospective studies, multi-institutional cohorts, and selected randomized trials suggests that a multimodal approach—combining systemic therapy with intraperitoneal or bidirectional chemotherapy—may improve survival and quality of life. In carefully selected patients whose primary gastric tumor and peritoneal lesions respond to systemic treatment, complete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) may further enhance outcomes and, in rare cases, achieve long-term survival. These potential benefits appear to be limited to highly selected patients with a low peritoneal tumor burden (PCI ≤ 6–7), positive cytology, good performance status, controlled extraperitoneal disease, and a high likelihood of achieving complete macroscopic cytoreduction (CC-0). Conclusions: Although the treatment intent in metastatic gastric cancer remains primarily palliative, carefully selected patients with limited peritoneal metastases may benefit from intensified multimodal treatment strategies when managed in specialized centers. Interdisciplinary evaluation, accurate staging, and individualized treatment planning are essential to optimize outcomes in this challenging disease setting. Full article

Chordoma is a rare malignant neoplasm of the axial skeleton, arising from notochordal remnants. No approved systemic therapies exist, and the 10-year overall survival is below 60%. Accurate molecular and pathological classification is a prerequisite for improved prognostication and the identification of actionable therapeutic targets; however, molecular classification of chordoma remains significantly less advanced than that of other neoplasms. This narrative review synthesizes proposed classification frameworks for chordoma across histological, radiological, surgical, genomic, epigenomic, transcriptomic, and proteomic domains. PubMed and CENTRAL were searched on 1 February 2026 using five queries: ‘chordoma classification’, ‘chordoma DNA sequencing’, ‘chordoma RNA sequencing’, ‘chordoma methylation’, and ‘chordoma copy number’. Original research articles describing more than one patient and reporting a classification or subtyping framework were included; review articles, case reports, and non-English publications were excluded. Sample size and the use of a validation dataset were identified for each study. Results were synthesized qualitatively. A total of 108 studies encompassing 6349 individuals were included. Across six domains, four cross-cutting themes with prognostic and potential theranostic value emerged: copy number alterations, particularly CDKN2A/B loss; SWI/SNF complex dysfunction; stroma–tumor ratio; and immune microenvironment heterogeneity. Full article

Research on the human microbiome, particularly the gut microbiome, has expanded rapidly as its influence on health and behavior becomes increasingly evident. Once understood primarily in terms of digestion and immune function, the microbiome is now recognized as a key contributor to brain function, mood regulation, and social behavior. Emerging evidence links microbial dysbiosis to the onset and persistence of mood disorders, opening new pathways for mental health research and intervention. This paper challenges reductionist biomedical models by advancing a biopsychosocial framework for interpreting health outcomes related to microbiome dynamics. The gut–brain axis illustrates the biological complexity of these interactions, with microbial communities shaping neurodevelopment and neurotransmitter production. Psychologically, alterations in microbial composition have been associated with depression, anxiety, and stress responsivity, while social determinants—including early-life environments, socioeconomic conditions, and relationships—structure microbial variation in ways that may reinforce existing health inequities. Focusing on women’s health, this narrative review examines how microbial states both influence and are shaped by interconnected biological, psychological, and social factors. Interdisciplinary implications of microbiome research for understanding and achieving eubiosis and holistic models care in both research and clinical practice are discussed. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with onset typically in early adulthood and the potential for long-term disability. Current therapies are initiated after symptom onset and do not address early disease triggers, highlighting the need for preventive strategies. Epstein–Barr virus (EBV) infection has emerged as the strongest candidate upstream factor in MS development. This narrative review provides a focused and critical synthesis of current evidence, with particular emphasis on the prevention perspective and the conceptual framing of MS as a potentially infection-driven disease. We integrate epidemiological, immunological, and mechanistic data while explicitly addressing key uncertainties and limitations in causal interpretation. Longitudinal studies indicate that EBV infection precedes MS onset in most cases and is associated with a markedly increased risk following seroconversion. However, EBV infection alone is not sufficient to cause MS. Proposed mechanisms include immune dysregulation and molecular mimicry, though key uncertainties remain. Based on current evidence, EBV represents a promising but unproven target for MS prevention. Future strategies may include prevention of EBV infection or infectious mononucleosis, alongside improved risk stratification and long-term studies to assess the impact of EBV-targeted interventions on MS incidence. Full article

It is well-known that immune checkpoint inhibitors (ICIs) can lead to uncommon but potentially life-threatening immune-related adverse events (irAEs) such as checkpoint-inhibitor pneumonitis (CIP). Early recognition, identification, and treatment are crucial with regard to decreasing toxicity from ICIs. However, there is a discrepancy in the incidence rates between the clinical trials and postmarketing studies. Several postmarketing studies have developed early detection methods and identified new risk factors in developing CIP. Thus, in this narrative review, we aim to review these incidence rates, early detection methods, and clinical risk factors for CIP in NSCLC patients, which could help to improve CIP diagnosis and management for enhanced NSCLC care. Major clinical trials and postmarketing studies of CIP incidence, early detection methods, and risk factors in NSCLC were reviewed. A wide array of potential risk factors has been implicated in the development of CIP in NSCLC, such as having preexisting interstitial lung disease, receiving PD-1 inhibitors, receiving combination ICI therapy instead of ICI monotherapy, lower pretreatment hemoglobin and albumin levels, increased baseline plasma IL-8 levels, and impaired baseline pulmonary function. Full article

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as potent modulators of immune responses during sepsis, yet their roles remain complex, alternating between protective and permissive depending on timing, tissue compartment, and inflammatory context. This review presents a historical assessment of VIP and PACAP in sepsis research, highlighting the evolution of conceptual advances across five decades. Starting in the 1980s, early studies revealed that VIP levels rise during endotoxemia and correlated with hypotension and mortality, suggesting a deleterious role. By the 1990s, research pivoted toward understanding gut-derived VIP and its interaction with nitric oxide, culminating in the classification of VIP and PACAP as “macrophage deactivating factors” that downregulate TNFα and IL-6. The 2000s further clarified their cell-specific actions through VPAC1/2 and PAC1 receptors, showing anti-inflammatory effects on both innate and adaptive immune cells, while illuminating delivery challenges overcome by liposomal encapsulation. The 2010s expanded this narrative by dissecting receptor dynamics, gut barrier regulation, and VIP’s role in neuroimmune crosstalk and thrombo-inflammation. Most recently, studies in the 2020s provide a nuanced view of how VIP suppresses inflammatory damage but also enables pathogen persistence during live bacterial infection, implicating VIP signaling in trade-offs between tolerance and clearance. Across this chronological framework, VIP and PACAP have oscillated between friend, foe, and frenemy, underscoring the importance of context in leveraging their therapeutic potential in sepsis. Full article