Search Results (5,208)

Background: Periprosthetic joint infections (PJIs), a significant complication of total knee replacement surgery, are influenced by patient, surgeon, and healthcare system factors. Natural disasters can disrupt healthcare services and alter microbiological factors in the hospital environment. The impact of natural disasters on pathogen distribution in periprosthetic joint infection (PJI) is unclear. Therefore, this study investigated the association between the 2023 Kahramanmaraş-centered earthquakes in Türkiye and changes in microbiological patterns of PJI after knee arthroplasty. Methods: This retrospective cohort study included patients who developed PJI following total knee arthroplasty at the study center. The patients were divided into two groups based on the timing of their PJI diagnosis: pre-earthquake and post-earthquake. The demographic characteristics, comorbid diseases, and perioperative characteristics of each patient were recorded, and their microbiological profiles were analyzed. Logistic regression analysis examined the relationships between patient-related factors and causative agents. Results: 56 patients were studied and divided into two groups: 26 patients in the pre-earthquake group and 30 in the post-earthquake group. Furthermore, 79 bacterial isolates were obtained from these patients. Demographic, metabolic, and preoperative characteristics were similar between the two groups. No significant difference was found in the overall distribution of bacterial isolates. However, Gram-negative organisms, primarily Acinetobacter baumannii and Pseudomonas aeruginosa, increased in the isolate distribution after the earthquake. Patient analysis revealed that polymicrobial PJIs were significantly more frequent after the earthquake (56.7% vs. 23.1%; p = 0.011). Diabetes mellitus (DM) and smoking were associated with an increased risk of polymicrobial infection; the association was not statistically significant. Conclusions: In the post-earthquake period, patients who had undergone total knee arthroplasty and developed PJI showed a higher proportion of polymicrobial infections and a numerical increase in Gram-negative pathogens, along with more complex infection patterns compared to the pre-earthquake period. Although both patient groups demonstrated similar characteristics regarding patient-related and surgical factors, the observed changes indicate that the pressure on the healthcare system after a natural disaster can affect a hospital’s microbiological ecology. Identifying these indirect effects is crucial for guiding microbiological surveillance and infection control during post-disaster recovery periods, even for elective patients. Full article

Background: Wastewater-based surveillance (WBS) has emerged as a valuable tool for population-level monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission, yet the interplay between sampling strategies and disease prevalence in shaping detection performance remains ambiguous. We investigated how grab and composite sampling influence SARS-CoV-2 ribonucleic acid (RNA) detection dynamics and predictive lag times across high- and low-prevalence communities in Selangor, Malaysia. Methods: A 28-week longitudinal study was conducted in Selangor, Malaysia, comparing grab and composite wastewater sampling in communities with high and low Coronavirus disease 2019 (COVID-19) prevalence. SARS-CoV-2 RNA in 348 samples was quantified using digital Reverse Transcription Polymerase Chain Reaction (RT-dPCR), and viral lineages were characterized by Nanopore sequencing. Detection sensitivity and lead times relative to reported cases were evaluated. Results: In low-prevalence settings, grab sampling showed higher detection sensitivity than composite sampling (92.0% vs. 70.0%), whereas both methods achieved similarly high detection in high-prevalence areas (>97.0%). Lag-time analysis indicated that grab sampling in high-prevalence settings was significantly associated with case trends at potential two-week lead (p = 0.024), while composite sampling in low-prevalence settings showed the strongest association at a potential one-week lead (p = 0.0022). Overall, lag structures varied by both sampling strategy and prevalence context. Both sampling approaches captured the replacement of Omicron sublineages (XBB.1.5, XBB.1.9.1, XBB.1.16) and identified additional circulating variants, including EG.5, that were not captured in the available clinical sequencing dataset during the same period. Conclusions: These findings reveal that local transmission intensity is associated with the utility of different sampling designs. Context-specific optimization of WBS sampling strategies enhances sensitivity, reduces detection lag, and strengthens early warning and genomic-tracking capacity in public health surveillance frameworks. Full article

Background and Objectives: New Caledonia, an archipelago in the South Pacific, experienced an unprecedented conjunction of prolonged border closure during the COVID-19 pandemic (2020 to 2022) and marked influence of the El Niño/Southern Oscillation (ENSO). This context provided a unique opportunity to explore how environmental drivers, island isolation, and socio-demographic factors interact to shape infectious disease dynamics. This study aimed to assess the respective and combined effects of climatic variability, travel restrictions, and socio-demographic factors on the dynamics of four priority infectious diseases. Materials and Methods: We retrospectively analysed data from 2017 to 2023 on four infectious diseases: leptospirosis, dengue, influenza, and hepatitis A (HAV). Satellite precipitation data and the Multivariate El Niño/Southern Oscillation Index (MEI) were used. Socio-demographic and economic variables were gathered. Statistical analyses employed descriptive analysis and Generalized Additive Mixed Models to evaluate the associations between climatic events, travel restrictions, and disease circulation using the communal level as a random effect and time (daily) as a spline effect. Results: We analysed 878 cases of leptospirosis, 165 of HAV, 6607 of influenza, and 7377 dengue cases. Influenza was associated with rainfall before lockdown (Odds Ratio (OR) 0.7, Confidence interval 95%, (CI95%), (0.6–0.8)) and disappeared during lockdown but resurged post-reopening losing its meteorological association. Dengue epidemics declined, coinciding with the Wolbachia program and border closure, and were associated with lower MEI (OR 0.78, CI95% (0.6–1) during the 2017 to 2020 period. HAV cases were correlated with the MEI (OR: 1.8, CI95% (1–3.3)). Leptospirosis cases were associated with cumulative rainfall (OR 1.12 (1.1–1.2)) and lower education (OR 1.04, CI95% (1–1.1)) and decreased with water supply (OR 0.7, CI95% (0.5–0.8)). Conclusions: Our findings highlight how climatic conditions, mobility restrictions, and socio-environmental inequities differentially shape infectious disease risks in island ecosystems. These results reinforce the need for integrated One Health surveillance that jointly addresses environmental change, social vulnerability, and infectious disease prevention. Full article

Background/Objectives: The hepatitis A virus (HAV) infection continues to represent a considerable public health issue in Eastern Europe, particularly in Bulgaria, where incidence rates exceed the EU average. This study sought to investigate the epidemiological and clinical aspects of acute hepatitis A in Southern Bulgaria between 2015 and 2023 and to assess changes during the COVID-19 pandemic period. Methods: A retrospective descriptive-analytic study was conducted among 1810 hospitalized patients with confirmed acute HAV infection at a tertiary infectious diseases center from 2015 to 2023. Demographic, clinical, laboratory, and temporal data were analyzed, comparing the pre-pandemic period (2015–2019) with the pandemic phase (2020–2023). Results: Most hospitalized cases occurred during the pre-pandemic period (88.0%), with epidemic peaks observed in 2016–2017. Individuals under 18 years comprised 69.9% of cases, with a median age of 9 years and a slight male predominance of 54.9%. A notable seasonal pattern was identified, characterized by peaks in autumn and early winter. Patients hospitalized during the pandemic period were significantly older compared with the pre-pandemic period (median age 14 vs. 8 years, p < 0.001). Adults experienced significantly longer hospitalization and higher ALT, AST, total bilirubin, and direct bilirubin levels compared with pediatric patients (all p < 0.001). The median duration of hospitalization was 7 days (IQR 6–10). Two in-hospital deaths were recorded, corresponding to a case fatality rate of 0.11%. Conclusions: Hepatitis A in Southern Bulgaria mostly impacts children but exhibits changing epidemiological trends, underscoring the necessity for focused preventative methods, such as vaccination and enhanced surveillance. Full article

Prostate cancer (PCa) is the second most frequently diagnosed solid malignancy in men and a major cause of cancer-related mortality worldwide. While localized disease is associated with excellent long-term survival, advanced and castration-resistant PCa continues to represent a major therapeutic challenge. Current management ranges from active surveillance for indolent tumors to multimodal systemic approaches for metastatic disease. In this context, natural compounds are attracting increasing interest as adjunctive or novel therapeutic agents. Among these, silymarin, a Silybum marianum-derived flavonolignan complex, has shown promising antineoplastic activity in preclinical PCa models. In vitro, silymarin compounds consistently inhibit PCa cell proliferation by inducing G1 and G2/M cell cycle arrest, upregulating cyclin-dependent kinase inhibitors, and activating caspase-dependent apoptotic pathways. They also modulate key oncogenic signaling pathways involved in cell survival, proliferation, invasion, and metastasis. In vivo xenograft and transgenic models further show reduced tumor growth, angiogenesis, and metastatic spread with limited systemic toxicity. Emerging clinical evidence, including systematic reviews and meta-analyses, suggests translational potential; however, robust randomized trials are needed to define optimal formulations, dosing strategies, and therapeutic efficacy in PCa patients. This review provides a comprehensive overview of the molecular mechanisms, preclinical efficacy, and emerging clinical evidence supporting silymarin as a candidate for future PCa research. Full article

Respiratory disease remains one of the mostly costly challenges in the U.S. swine industry and is frequently associated with polymicrobial infections. Routine qPCR assays are highly sensitive but are limited in multiplexing capacity and generally do not provide sequencing information for pathogen characterization. We hypothesized that a target next-generation sequencing (tNGS) panel could provide the broad, simultaneous detection of swine respiratory pathogens while preserving clinically relevant sensitivity. A multiplex Ion Torrent tNGS panel was developed and analytically validated using 20 serially diluted qPCR-positive clinical samples and synthetic gBlock controls, followed by diagnostic validation with 25 qPCR positive and 25 qPCR negative respiratory samples. Most targets were detected across clinically relevant pathogens concentrations. Actinobacillus suis primers showed nonspecific amplification, streptococcus suis serotyping was not consistently achievable in clinical samples, and porcine reproductive and respiratory syndrome virus typing was limited to distinguishing North American and European genotypes. Diagnostic agreement with routine qPCR was high (Cohen’s κ = 0.84), although sensitivity decreased for low-abundance targets. The assay detected mixed infections and additional organisms outside routine qPCR panels. These findings support tNGS as a complementary diagnostic and surveillance tool for swine respiratory disease. Full article

Sickle cell disease (SCD) is a monogenic disorder responsible for recurrent vaso-occlusive crises, progressive organ damage, and shortened life expectancy. For decades, allogeneic hematopoietic stem cell transplantation from a matched sibling donor has been the only established cure, but its reach remains limited by donor availability and transplant-related toxicity. The approval of two autologous gene therapy products in 2023, exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel), marked a turning point for the SCD population and the gene therapy field in general. This review proposes a molecular rationale for fetal hemoglobin reactivation and β-globin gene addition, describes the engineering of lentiviral and CRISPR-based platforms, and highlights the clinical evidence accumulated to date that demonstrated durable disease modification with acceptable short-term toxicity. We then assess the clinical positioning of gene therapy within the broader spectrum of curative options compared to current available treatments and address the financial, ethical and psychosocial barriers that limit access to gene therapy both within high-income countries and globally. Critical research priorities include long-term safety surveillance, comparative effectiveness studies, pediatric trials below 12 years, and validated patient-reported outcome instruments. Base editing, non-genotoxic conditioning, and in vivo delivery represent the most promising avenues to broaden access and reduce treatment burden. Full article

Background/Objectives: Artificial intelligence (AI) is rapidly transforming healthcare. Its integration into community health nursing—a discipline centered on population-level prevention, health promotion, and primary care in community settings—remains insufficiently explored. This narrative review examines the opportunities, ethical challenges, and future directions for integrating AI into community health nursing education and practice. Methods: A literature search was conducted across PubMed, CINAHL, Scopus, Web of Science, and IEEE Xplore for publications between January 2017 and March 2026. The initial search yielded 612 records; after the removal of duplicates and screening of titles, abstracts, and full texts against predefined criteria, 58 sources were retained for thematic synthesis, comprising empirical studies, systematic and umbrella reviews, scoping reviews, meta-analyses, and authoritative policy documents. Screening and data extraction were performed by two reviewers, with disagreements resolved by discussion. Results: AI offers opportunities for community health nursing across four interconnected domains: clinical decision support for community-based assessments, predictive analytics for population health management, enhanced disease surveillance and outbreak detection, and personalized health education delivery. Significant challenges persist, including algorithmic bias, data privacy concerns, threats to the therapeutic nurse–client relationship, inadequate AI literacy among nursing faculty, and regulatory gaps. Most empirical evidence originates from hospital or general nursing settings; transferability to community contexts is therefore inferred rather than directly demonstrated. Conclusions: Responsible integration of AI into community health nursing requires curriculum reform, ethical governance frameworks, faculty development, equitable access, and interdisciplinary collaboration. AI should augment, not replace, the relational and culturally sensitive care that defines this discipline. Given the narrative nature of the review and the limited community-specific evidence, conclusions are framed as a vision of the AI–community health nursing interface rather than a definitive synthesis. Full article

Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective. Full article

Background: Hypertension is one of the most prevalent comorbidities in patients with COVID-19 and a major contributor to chronic kidney disease (CKD). Traditional kidney injury markers, including creatinine, estimated glomerular filtration rate (eGFR) and microalbuminuria, reflect renal injury only after substantial nephron loss has already occurred. Urinary podocyte proteins, such as nephrin (nephrinuria), have been suggested as early markers of glomerular barrier dysfunction; however, their clinical behavior and diagnostic value in hypertensive patients with previous SARS-CoV-2 infection are unknown. Aim: To assess urinary nephrinuria, microalbuminuria, transforming growth factor β1 (TGF-β1), aldosterone, vascular endothelial growth factor A (VEGF-A) and renal hemodynamics across different stages of hypertension in patients with and without a history of COVID-19 and to assess the response to conventional antihypertensive and nephroprotective treatment. Methods: In a prospective comparative cohort study, 120 patients (aged 30–60 years) with stage I–III essential hypertension were stratified by COVID-19 history into a post-COVID-19 group (n = 60) and a non-COVID-19 group (n = 60); within each group, 20 patients were assigned to each hypertension stage. Comparisons were performed between the post-COVID-19 and non-COVID-19 subgroups at the same hypertension stage. Serum creatinine, cystatin-C, aldosterone, TGF-β1 and VEGF-A, urinary microalbumin and nephrin and intrarenal Doppler hemodynamics were measured at baseline and after six months of guideline-based treatment. Results: Nephrinuria was markedly increased in post-COVID-19 patients in all stages of hypertension, including stage I, where serum creatinine, cystatin-C and eGFR were within the normal range (126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01). Nephrinuria was strongly correlated with renal functional reserve (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001), microalbuminuria (r = 0.758, p < 0.001), aldosterone (r = 0.613, p < 0.001) and VEGF-A (r = 0.589, p < 0.001). Antihypertensive and nephroprotective treatment for six months decreased nephrinuria, blood pressure and TGF-β1, with more limited effects in stage III disease. Conclusions: Nephrinuria was found to be an early marker of renal involvement in COVID-19, occurring before microalbuminuria and conventional functional markers and with a greater relative difference than these markers in stage I disease, suggesting podocyte injury as an early and potentially reversible mechanism of post-COVID renal involvement in hypertensive patients. Nephrinuria seems to be a potential biomarker for early renal surveillance in this population and its prognostic role for incident CKD needs to be validated in longitudinal outcome studies. Full article

Environmental health services play a critical role in communicable disease outbreaks by addressing environmental determinants of disease transmission. However, the scope, impact, and challenges of Environmental Health Practitioner (EHP)-led interventions remain insufficiently documented. Aim and objectives: This systematic review objectively assessed the role, impacts, and challenges of municipal environmental health services in outbreak response, with a focus on South Africa, to inform the standardisation and strengthening of disease surveillance and prevention. Methods: The PICO framework guided the development of search terms and research questions. PubMed, Scopus, Google Scholar, and Web of Science were searched for English-language, full-text studies published between 2010 and 2024. Studies not meeting these inclusion criteria were excluded. Screening and reporting followed PRISMA guidelines, and data were synthesised using a standardised extraction tool. Results: A total of 58 studies were included. The key EHP functions identified were water quality monitoring, vector control, food safety, waste management, and outbreak response. While South Africa demonstrated comparatively advanced systems, persistent implementation challenges remain, including the integration of environmental monitoring with disease surveillance. The findings emphasised the need for integrating environmental monitoring with disease surveillance systems and integrating WASH and climate-responsive strategies. Conclusions and recommendation: The review recommends strengthening guidelines and advancing evidence-based practice. Enhancing EHP roles within surveillance frameworks is essential for improving outbreak preparedness and public health resilience. Full article

Background/Objectives: Vaccine development pipelines are forward-looking indicators of public health preparedness, reflecting the capacity to address unmet medical needs and emerging threats. This descriptive analysis aims to characterise the 2025 clinical-stage pipeline of infectious disease vaccines and prophylactic monoclonal antibody candidates developed by Vaccines Europe member companies, and to describe how pipeline characteristics address evolving public health priorities. Methods: A descriptive analysis was conducted using publicly available data compiled in the Vaccines Europe Pipeline Review 2025, with validation by participating companies. Candidates in clinical development or regulatory review were classified using a standardised framework by pathogen/disease, target population, public health priority, and technologies. Results: The Vaccines Europe member company pipeline comprises 91 candidates across clinical development phases, 19% of which are in Phase III and 7% undergoing regulatory review. This pipeline is predominantly targeting respiratory pathogens (75%), with a strong life-course focus (85% evaluated in adults and/or older adults), and sustained activity in bacterial pathogens relevant to antimicrobial resistance. Notably, 41% of candidates were classified as addressing diseases, disease combinations, or indications for which no licenced preventive product exists. This category includes candidates targeting diseases without a preventive solution, as well as novel combination vaccines and therapeutic approaches in areas where individual components or preventive vaccines are already available. This captures vaccines candidates in different stages of development, not necessarily first-in-disease innovation. The pipeline shows broad technological diversity (12 technologies), dominated by RNA approaches and multivalent candidates, with growing focus on climate-sensitive, zoonotic, and pandemic-prone pathogens. Conclusions: Within the pipeline of Vaccines Europe member companies, this analysis describes development activity oriented toward broader prevention, platform-based approaches, and preparedness-relevant targets. As a structured and recurring annual assessment, the Vaccines Europe Pipeline Review supports horizon scanning and evidence-based dialogue between industry and vaccine ecosystem stakeholders. In order to maximise the impact of vaccine development pipelines to public health, predictable investment, streamlined trial and regulatory pathways, strong surveillance, and real-world data systems, coordinated decision-making is required to enable timely and equitable access, and complementary incentive and procurement reforms. Full article

Heritable thoracic aortic diseases (HTAD) are inherited conditions that increase the risk of thoracic aortic aneurysms, dissections, and premature aortic rupture. Advances in human genetics and experimental models have transformed our understanding of these disorders from a phenotype-based classification system to a mechanism-based view involving extracellular matrix (ECM) architecture, transforming growth factor-β (TGFβ) signaling, and vascular smooth muscle cell contractility. Marfan syndrome, Loeys–Dietz syndrome, and nonsyndromic HTAD demonstrate how genetic mutations can disrupt the components that stabilize the aortic wall. These pathogenic mechanisms influence matrix organization, intracellular signaling, and the contractile machinery within the mechanically stressed proximal aorta. In this review, we summarize current mechanistic insights into the major forms of HTAD and discuss how new molecular and cellular concepts could influence surveillance, genetic counseling, and genotype-guided therapeutic strategies. Full article

Background: Streptococcus pneumoniae may asymptomatically colonize the human nasopharynx and remains a leading cause of invasive and noninvasive disease in children, accounting for an estimated 294,000 global deaths in those aged under five years. Nationally representative serotype data from Indonesia remain limited despite national PCV13 rollout in 2022. This study aims to evaluate the distribution of Streptococcus pneumoniae serotypes and estimate the coverage of pneumococcal conjugate vaccines (PCVs) among children aged 0–18 years in Indonesia. Methods: Systematic search of PubMed, Scopus, ScienceDirect, Google Scholar, and Paediatrica Indonesiana (to December 2025) for observational studies (PROSPERO CRD420251239935). The extracted data included the study period, setting, population, specimen type, serotypes, sample size, and nasopharyngeal carriage. Pooled serotype prevalence is calculated; vaccine coverage estimated for pneumococcal conjugate vaccines containing 10 (PCV10), 13 (PCV13), 15 (PCV15), and 20 (PCV20) serotypes assuming vaccine-type priority in multicolonization. Risk of bias assessed using the Joanna Briggs Institute’s checklist for prevalence studies. Results: Nineteen studies across 13 regions of Indonesia involving children aged 0–18 years included. Nasopharyngeal carriage ranged from 21.0% to 87.6% in healthy children and 9.2% to 73% in children with illnesses. The most common serotypes were 19F, 23F, 6B, 14, 19A, and 34. Non-typeable isolates accounted for more than 20% of all isolates in several studies. The pooled coverage for PCV10, PCV13, PCV15, and PCV20 was 40.3%, 50.2%, 50.8%, and 57.0% respectively. Low-moderate RoB (63% low). Conclusions: The dominant serotypes largely included in PCV13. Active surveillance is required to monitor serotype shifts and ensure the long-term effectiveness of the national vaccination program. Full article

Background: Orbital rhabdomyosarcoma (RMS) is the most common primary pediatric malignant orbital tumor, typically curable with chemotherapy and radiation. Data regarding MRI chemotherapy response and long-term ophthalmologic outcomes remain limited in non-cooperative-group settings. Methods: We retrospectively reviewed children with primary orbital RMS treated at King Hussein Cancer Center (2002–2025) with vincristine, actinomycin-D, and cyclophosphamide (VAC). Pre-local-control MRI responses were classified as complete (CR), partial (PR), stable/minor (SD/MR), or progressive disease (PD). Survival and ophthalmologic outcomes were analyzed. Results: Twenty-two patients (median age 5.6 years) were included. All had localized disease (77% low-risk). All received VAC; 20 (91%) received radiotherapy (median 45 Gy). Pre-radiotherapy MRI showed 8 (36%) CR and 11 (50%) PR. Four patients (18%) died. Five-year event-free survival (EFS) and overall survival (OS) were 73% and 84%, respectively. Cataracts developed in 45% of the cohort (50% of irradiated patients) at a median of 39.1 months (range 9.4–95.1). At last assessment, visual acuity was good in 60%, moderate in 25%, and severely impaired in 15%. Conclusions: Excellent survival in orbital RMS is achievable in resource-stratified settings. Induction MRI progressive disease (PD) was associated with poor outcomes in this cohort and may represent an early prognostic signal warranting further validation in larger studies. Furthermore, the documented maximum cataract latency of 95 months suggests that the standard 5-year surveillance window is insufficient. These findings support extending ophthalmologic surveillance beyond the standard 5-year window. We propose, based on our retrospective institutional data, a 10-year functional survivorship framework. Full article