Search Results (7,127)

Background: The etiological diagnosis of chronic thrombocytopenia in children remains challenging and is often established by exclusion. In this article, we present the case of a patient in whom we used whole-exome sequencing (WES) to help identify the underlying cause and determine the appropriate treatment. Methods: Whole-exome sequencing was performed to clarify the genetic background of the disease. Based on the results, transmission electron microscopy (TEM) was also carried out to confirm or exclude the pathogenic role of the identified NBEAL2 gene variant and to assess the presence of gray platelet syndrome. Results: In this patient, despite the presence of the NBEAL2 gene variant, neither gray platelet syndrome nor a pathogenic role of the variant could be confirmed. However, the genetic findings identified by WES led to numerous additional investigations, causing a considerable burden on both the patient and the family. Conclusions: Our case highlights that WES testing, which is emerging in pediatric hematology practice, offers not only diagnostic advantages but also pitfalls. Whole-exome sequencing has recently emerged as a new diagnostic tool and has been available nationwide in pediatric hematology-oncology care in Hungary for just over two years. While personalized treatment strategies for benign hematologic diseases increasingly rely on high-throughput genetic testing, the clinical application of WES requires a cautious, critical evaluation of results. Despite the method’s promise, the heterogeneity of the findings underscores the need to interpret WES results carefully and to place them in a clinical context in every case. Full article

Background/Objectives: Adolescents admitted for emergency psychiatric hospitalization frequently present with severe and heterogeneous psychopathology. In clinical practice, some adolescent inpatients appear to present a broader symptom pattern suggestive of emotional dysregulation. However, it remains unclear whether they can truly be distinguished in this population and whether they differ meaningfully from adolescents with predominantly depressive presentations. Methods: We conducted a retrospective cross-sectional chart review with subgroup analysis based on the medical records of patients aged 11–17 years hospitalized on an emergency basis at the Department of Child and Adolescent Psychiatry in Poznań, Poland, between January and December 2024. Patients were assigned either to an emotional dysregulation group, defined by affective dysregulation and behavioral dyscontrol, or to a depressive presentations group, comprising adolescents with depressive presentations who did not meet criteria for the emotional dysregulation profile. Broader clinical characteristics, adverse childhood experiences, and prior treatment history were compared between groups. Results: A total of 139 adolescents were included (85 in the emotional dysregulation group and 54 in the depressive presentations group). The median age was 13 years [Q1–Q3: 13–14] in the emotional dysregulation group and 14 years [Q1–Q3: 12.25–14] in the depressive presentations group; girls comprised 77.6% and 83.3% of the groups, respectively. The emotional dysregulation group more often presented with conflict-ridden relationships, a more frequent history of suicide attempts (72.9% vs. 50.0%, p = 0.006), and a higher number of suicide attempts (median 1 [Q1–Q3: 0–2] vs. 0.5 [Q1–Q3: 0–1], p = 0.012), as well as more frequent exposure to adversity-related experiences. Furthermore, this group had a higher number of previous psychiatric hospitalizations (median 1 [Q1–Q3: 1–2] vs. 1 [Q1–Q3: 1–1], p = 0.001) and a longer history of psychiatric treatment. In contrast, social withdrawal was more characteristic of the depressive presentations group. Conclusions: Routinely collected clinical records may capture a clinically meaningful subgroup of adolescents with a symptom profile suggestive of emotional dysregulation. Compared with the depressive presentations group, these adolescents showed greater interpersonal difficulties, more recurrent suicide attempts, greater adversity burden, and a longer history of psychiatric treatment. Further prospective studies using standardized measures are needed. Full article

Background: CD56 expression has been proposed as a prognostic and predictive biomarker in multiple myeloma. However, its clinical relevance in the context of modern induction therapy and autologous stem cell transplantation (ASCT) remains controversial. Methods: The researchers studied individuals with newly diagnosed multiple myeloma. CD56 expression was assessed by flow cytometry at diagnosis. Assessment was performed to determine patients’ responses to induction therapy and to measure their progression-free and overall survival rates. Results: The study included 88 participants, of whom 68 (77%) were CD56-positive, and 20 (23%) were CD56-negative. The study results showed that CD56(−) patients developed plasmacytomas at a 70% rate, while CD56(+) patients had a 46% rate (p = 0.055). A similar pattern was observed for extramedullary lesions (p = 0.006). The induction response rate was lower in CD56-negative patients than in CD56-positive patients (65% vs. 85%, p = 0.043). Patients who did not experience relapse received more CD34⁺ cells (11.9 ± 5.71 vs. 9.29 ± 2.57 × 10⁶/kg, p = 0.012) and had higher post-transplant response rates (91% vs. 63%, p = 0.002). The patients who received induction treatment before their disease showed better survival outcomes than patients who did not respond to treatment (90.2% vs. 87.1%, p = 0.029) and patients who did not experience relapse (92.7% vs. 85.0%, p = 0.022). CD56 status did not affect survival outcomes. Conclusions: CD56 expression is associated with disease burden and response to induction therapy in multiple myeloma, supporting its role as an early disease-modifying factor. However, its prognostic value appears limited in patients receiving high-dose chemotherapy with ASCT, suggesting that intensive treatment may mitigate the adverse impact of CD56 negativity. Full article

Cardiovascular diseases have high mortality rates and present a high burden on society and the global healthcare system. A large quantity of drugs have been developed, such as aspirin, ACE inhibitors, beta-blockers, and statins. Although these traditional drugs have decreased the morbidity and mortality of cardiovascular diseases, they still have multiple limitations. Due to their shortcomings, researchers have continued to search for novel targets for drug treatment. The tripartite motif (TRIM) protein family is a superfamily with E3 ubiquitin ligase activity and involves diversified processes including proliferation, development, signal transduction, and immune regulation. The latest research has shown that TRIM proteins participate in the progression of cardiovascular diseases, such as cardiac hypertrophy, cardiac ischemia–reperfusion injury, heart failure, hypertension, atherosclerosis, and so on. In this review, we summarize the structure and function of TRIM proteins, as well as the mechanisms of their involvement in various cardiovascular diseases, aiming to raise awareness of the importance of TRIM proteins in cardiovascular disease research and treatment. Advancing our understanding of mechanisms mediated by TRIM proteins may emphasize their contributions to cardiovascular diseases and provide the opportunity to develop novel and targeted therapeutic strategies to combat cardiovascular diseases. Full article

Background: Tuberculosis (TB) remains a major public health challenge globally, particularly in high-burden countries such as South Africa. Treatment interruption is a critical barrier to effective TB control, contributing to poor treatment outcomes, increased risk of multidrug-resistant tuberculosis (MDR-TB), and continued community transmission. Understanding the determinants of treatment interruption in rural healthcare settings is essential for strengthening TB programme implementation. Methods: This qualitative study explored the factors influencing TB treatment interruption from the perspectives of professional nurses working in primary healthcare facilities in the Nyandeni Subdistrict, Eastern Cape, South Africa. Semi-structured interviews were conducted with nurses involved in TB programme implementation. Data were analysed using thematic analysis following the six-phase approach described by Braun and Clarke. Descriptive statistical analyses were also used to summarize participant characteristics, including age and years of nursing experience. Conceptual frameworks were developed to illustrate the multilevel determinants of TB treatment interruption. Results: Participants had a mean age of 40.6 years and an average of 14.2 years of nursing experience, reflecting a workforce with substantial clinical exposure to TB management. Thematic analysis identified multiple interconnected determinants of treatment interruption. Key barriers included poverty, food insecurity, transport costs, long distances to healthcare facilities, limited family support, and challenges related to patient tracing. These factors interact across structural, community, health system, and interpersonal levels to influence patient adherence behaviour. Conceptual models developed from the findings illustrate the complex pathways through which these determinants contribute to treatment interruption and programme-level consequences such as reduced treatment success and increased risk of MDR-TB. Conclusions: TB treatment interruption in rural settings is driven by multilevel socioeconomic and health system determinants rather than individual patient behaviour alone. Strengthening community health worker programmes, improving patient tracing systems, addressing socioeconomic barriers, and enhancing community-based support mechanisms are essential for improving treatment adherence. Integrated, multisectoral interventions are required to strengthen TB programme outcomes in rural high-burden settings. Full article

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC. Full article

Background: Tuberculosis (TB) remains a major cause of morbidity and mortality among children worldwide, with approximately one million new pediatric cases annually. The conventional treatment for drug-susceptible TB has long relied on a 6-month multidrug regimen, which is highly effective but associated with challenges in adherence, toxicity, and healthcare burden. Objectives: To evaluate whether short-course therapy is an appropriate regimen for children and young adolescents with drug-susceptible TB, with particular focus on its efficacy, safety, and applicability in different clinical contexts. Methods: A structured narrative review of the literature was conducted, including randomized controlled trials, observational studies, and international guidelines addressing treatment duration in children and young adolescents with drug-susceptible TB. Evidence was synthesized focusing on children and young adolescents <16 years with drug-susceptible TB treated with short-course regimens compared to standard therapy. Results: A shorter treatment regimen, particularly 4-month courses, has been investigated as an alternative to standard therapy in the pediatric population with drug-susceptible TB. Children often present with paucibacillary and non-severe forms of TB, providing a biological rationale for treatment shortening. Evidence from a randomized controlled trial has demonstrated that a 4-month regimen is non-inferior to the standard 6-month therapy in children and young adolescents with non-severe, drug-susceptible TB. These findings have informed recent international guideline updates, which now recommend short therapy in carefully selected patients. However, a short regimen is not appropriate for infants younger than 3 months, children with severe or complicated TB, extrapulmonary disease such as central nervous system involvement, or those with drug-resistant TB. The overall quality of evidence remains moderate, and long-term relapse data are still emerging. Conclusions: Short-course therapy represents a promising but selective strategy in pediatric drug-susceptible TB management. It offers potential advantages, including improved adherence, reduced drug toxicity, and lower healthcare costs. However, its safe implementation requires accurate patient selection, access to appropriate diagnostic tools, and structured follow-up. Careful application within clearly defined clinical criteria is essential to ensure optimal outcomes. Full article

American Indian and Alaska Native (AI/AN) populations experience disproportionately high kidney cancer incidence and mortality compared to other groups in the United States. Literature was reviewed to explore the factors contributing to the unequally higher kidney cancer burden in AI/AN communities and to develop recommendations to reduce these disparities. The incidence of kidney cancer has been rising over the past few decades, and this increase has been especially steep among AI/AN populations. Death rates in AI/AN populations are roughly twice those of the non-Hispanic White population. The elevated kidney cancer burden in AI/AN populations may be driven by both clinical and behavioral risk factors (obesity, diabetes, hypertension, chronic kidney disease, smoking, and environmental factors) and structural drivers of health, which can critically shape these disparities. Systemic inequalities limit AI/AN patients and community members’ access to chronic disease management, smoking cessation programs, primary and specialty care for early detection, and ultimately, treatment. AI/AN patients may have mistrust or other cultural barriers to engaging with the healthcare system and providers, while implicit bias in healthcare providers may lead to undertreatment. Therefore, key interventions and tailored programs aimed at reducing kidney cancer incidence and mortality are needed. Here we highlight some current interventions, including access to disease management and smoking cessation programs, facilitating healthcare access and quality, adopting patient navigation and culturally competent education, and developing strategies for early detection. In partnership with AI/AN communities, a combination of prevention, early detection, and healthcare system improvements is needed to close the kidney cancer gap. Full article

There is a well-documented gap between the prescription of adrenaline auto-injectors (AAIs) and their real-world use during anaphylaxis. Although several aspects of AAI underuse have been investigated, the potential role of shelf life in influencing patient adherence has not been quantified. This study assessed the real-world remaining shelf life of AAIs available at pharmacies in Denmark, Finland, Sweden, and Norway, using pharmacy-level stock data and pharmacy employee-reported perceptions. Across Denmark, Finland, and Sweden, the average remaining shelf life was 9.6 months, and in Norway it was 10.5 months at the point of dispensing. In Denmark, Finland and Sweden, 100%, 91%, and 94% of employees, respectively, considered shelf life an important or very important factor when dispensing AAIs to patients. Our findings suggest that patients and caregivers filling prescriptions for AAIs frequently receive devices with limited remaining shelf life, which may necessitate multiple renewals per year. This has potential implications in terms of adherence to clinical guidelines, dependence of expired devices during emergencies, patient cost, caregiver burden, and overall societal expenditure. These results highlight an unmet need for emergency treatment options with longer shelf life to better support continuous access to life-saving medicine during anaphylaxis. Full article

Retinopathy of Prematurity (ROP) affects preterm infants worldwide, involving abnormal development of retinal blood vessels associated with supplemental oxygen use in neonatal care. Although there have been strides in identifying at-risk infants, implementing early screening, updating disease criteria through the International Classification of Retinopathy of Prematurity (ICROP), and developing new therapies, ROP remains a leading cause of preventable blindness. As preterm birth survival rates rise, the incidence of ROP continues to increase and is projected to rise even in countries with abundant resources and well-established care programs. Improving ROP care requires global standardization of screening, diagnosis, and management to prevent missed diagnoses and minimize outcome variability. Intravitreal anti-vascular endothelial growth factor (VEGF) injections are changing the landscape of ROP management, but longitudinal research is needed to determine their long-term safety in preterm infants. Effective ROP management relies on teamwork across disciplines and open communication with parents. Given that parents are lifelong caregivers of a child who may be affected by ROP-related vision impairment, including them in the care team and encouraging psychosocial support is vital. Socioeconomic disparities and limited access to ROP-trained ophthalmologists exacerbate disease burden, underscoring the need for innovative solutions to improve access to care. This perspective emphasizes the importance of globally standardizing ROP prevention and care, noting that efforts are still incomplete, equitable access has not been realized, and the long-term role of anti-VEGF agents in ROP treatment remains unclear. Full article

Background/Objectives: Childhood non-cystic fibrosis (non-CF) bronchiectasis is clinically heterogeneous. We aimed to describe fractional exhaled nitric oxide (FeNO) levels in affected children and examine associations with etiology, spirometry, and CT-defined disease extent. Methods: This single-center prospective observational study included 100 clinically stable children aged 6–18 years with CT-confirmed non-CF bronchiectasis evaluated between September 2014 and December 2015. FeNO was measured before spirometry using an online single-breath electrochemical technique. Chest CT was reviewed at the lobar level, with the lingula counted separately, and disease extent was summarized by the number of involved lobar regions. Associations were assessed using Spearman correlation and non-parametric tests. Results: Mean age was 14.9 ± 2.0 years, 55% were male, and mean FeNO was 20.9 ± 14.0 ppb. FeNO correlated positively with FEV1 (% predicted), FVC (% predicted), and FEF25–75 (% predicted) (all p < 0.01). FeNO was higher in males and adolescents than in females and younger children, respectively. FeNO did not differ by CT-defined lobar extent. It was lower in primary ciliary dyskinesia than in asthma overlap. Overall, 82% of the cohort received an ICS-containing maintenance regimen and household tobacco smoke exposure was present in 58%. Conclusions: FeNO was associated with selected functional indices and etiologic subgroups, but not with CT-defined structural extent, suggesting a greater role in clinical phenotyping than in reflecting radiologic burden. Rather than reflecting overall disease severity, FeNO may be more relevant as a marker of T2-leaning airway inflammatory phenotype in selected children with non-CF bronchiectasis. These findings should be interpreted as exploratory and hypothesis-generating, particularly for etiologic subgroup comparisons and for FeNO interpretation in the setting of treatment and environmental confounding. Full article

Life cycle assessment (LCA) is an important analytical method used to evaluate the environmental impacts of products, services, or processes throughout their entire life cycles—from the extraction of raw materials and production to use and end-of-life treatment. LCA enables the identification of stages with the highest environmental impact burden (hotspots) and supports strategic environmental initiatives, the circular economy, standards, and policies aimed at improving sustainability. This paper analyses the application of LCA in metallurgy, with a focus on primary aluminium production. It outlines the principles of life cycle thinking and explores decarbonisation opportunities within the aluminium industry. This study includes a life cycle impact assessment case study comparing the most significant environmental impacts of primary aluminium production in different regions of the world, including Europe and Asia. The analysis was performed using openLCA software 2.5 with the OzLCI2019 database. Environmental impacts were calculated using the ReCiPe 2016 Midpoint (H) method. The results indicate that primary aluminium production mainly affects impact categories related to high energy consumption, the use of carbon anodes, and associated emissions. The highest impacts were identified in ecotoxicity, followed by global warming, land use, ozone formation, and fossil resource scarcity. No significant regional differences were observed. Full article

Background/Objectives: Camellia bee pollen refers to pollen pellets collected by bees from plant stamens and mixed with salivary secretions. Alcoholic fatty liver disease (AFLD), as the initial phase within the spectrum of alcohol-induced liver diseases, has resulted in a rising global incidence rate and treatment burden of such liver ailments. Methods: This study employs acute zebrafish juvenile and adult zebrafish chronic alcoholic liver models to explore the protective effects of camellia bee pollen as well as its ethanol and water extracts on zebrafish alcoholic fatty liver. Results: The research findings indicate that the intervention group treated with camellia bee pollen significantly mitigated the accumulation of lipid droplets in zebrafish larvae and notably improved the liver lobule structure of adult zebrafish, bringing it close to normal conditions. The camellia pollen intervention group could significantly decrease the levels of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), while increasing the levels of glutathione (GSH) and total superoxide dismutase (T-SOD). Conclusions: This experiment indicates that the pollen of tea flowers has a significant protective effect against alcoholic liver damage. Full article

Hepatitis C virus (HCV) infection is still a major worldwide health concern. It is distinguished by a high degree of genetic variation that affects the course of the illness and the effectiveness of treatment. The epidemiological profile of HCV is prone to rapid change in areas where there is significant human migration, like Turkey. The purpose of this study was to evaluate the impact of long-term migration on local viral diversity by analyzing the distribution and temporal trends of HCV genotypes among Turkish citizens and asylum seekers in Kayseri, Turkey, over an eight-year period. From January 2014 to December 2021. 1173 HCV RNA-positive patients at Kayseri City Training and Research Hospital were the subject of a retrospective analysis. Genotypes were determined using the Abbott RealTime HCV Genotype II assay and Montania 4896 assay (Anatolia Geneworks, Türkiye). The most prevalent genotypes were Genotype 1b (48.3%, 95% CI: 45.5–51.2%), Genotype 4 (25.0%, 95% CI: 22.5–27.5%), and Genotype 1a (10.3%, 95% CI: 8.6–12.1%). Turkish patients exhibited the highest prevalence of Genotype 1b (98.2%), while asylum seekers demonstrated greater relative burdens of Genotype 4 (8.5% of total GT4) and Genotype 5 (83.3% of total GT5). Genotype 3a emerged in 2018, with a predominance in males (73.9%). The Cochran–Armitage trend test revealed statistically significant increasing trends for Genotype 3 (Z = 3.572, p = 0.0004) and Genotype 3a (Z = 2.600, p = 0.009). This eight-year retrospective study demonstrates that the HCV genotype distribution in Kayseri has undergone significant changes in the context of migration and demographic shifts. The statistically significant increasing trends of Genotypes 3 and 3a, particularly among younger male populations, suggest evolving transmission dynamics. These findings underscore the necessity of demographically targeted and culturally appropriate screening and treatment strategies for both resident and migrant populations to achieve HCV elimination goals. Full article

Silver diamine fluoride (SDF) is a key preservation-based intervention in pediatric dentistry. It can arrest many cavitated lesions, reduce treatment burden, and expand access for children who cannot receive conventional restorative care. This viewpoint article offers a reasoned, heuristic framework for calibrating SDF guidance to the strength of the underlying evidence. It does not present a systematic review or formal policy standards. Foundational trials support the clinical usefulness of 38% SDF. The 2017 AAPD guidelines provided conditional recommendations based on low-quality evidence. The current challenge is no longer whether to endorse SDF but how to calibrate guidance on its implementation. Later studies addressing intervals and implementation often have open-label designs, small samples, single centers, or overlapping data sources. Mechanistic and microbiome studies support biological plausibility, but policy should not treat them as definitive evidence. We propose a hypothesis-generating framework that separates claims about the existence of an effect (for which there is stronger directional support) from claims about its optimal conditions (which remain more uncertain), highlights dataset overlap, and matches recommendation strength to study quality. The framework supplements GRADE and provides illustrative upgrade pathways. The goal is to preserve SDF access while making guidelines more transparent, credible, and precise. Full article