Search Results (2,405)

Background: Advances in molecular pathology have transformed NSCLC (Non-Small Cell Lung Cancer) diagnosis, prognosis, and treatment by enabling precise tumor characterization and targeted therapeutic strategies. We review key genomic alterations in NSCLC, including EGFR (epidermal growth factor receptor) mutations, ALK (anaplastic lymphoma kinase) and ROS1 (ROS proto-oncogene 1) rearrangements, BRAF (B-Raf proto-oncogene serine/threonine kinase) mutations, MET (mesenchymal–epithelial transition factor) alterations, KRAS (Kirsten rat sarcoma) mutations, HER2 (human epidermal growth factor receptor 2) alterations and emerging NTRK (neurotrophic receptor tyrosine kinase) fusions and AXL-related pathways. Methods: A total of 48 patients with NSCLC was analyzed, including 22 women and 26 men (mean age 70 years, range 44–86). Tumor specimens were classified histologically as adenocarcinomas (n = 81%) or squamous cell carcinomas (n = 19%). Smoking history, PD-L1 (programmed death-ligand 1) expression, and genetic alterations were assessed. NGS (Next-generation sequencing) identified genomic variants, which were classified according to ACMG (American College of Medical Genetics and Genomics) guidelines. Results: The cohort consisted of 29 former smokers, 13 current smokers, and 5 non-smokers (12%), with a mean smoking burden of 33 pack years. PD-L1 TPS (tumor proportion score) was ≥50% in 10 patients, ≥1–<50% in 22, and <1% in 15 patients. In total, 120 genomic variants were detected (allele frequency ≥ 5%). Of these, 52 (43%) were classified as likely pathogenic or pathogenic, 48 (40%) as variants of unknown significance, and 20 (17%) as benign or likely benign. The most frequently altered genes were TP53 (tumor protein p53) (31%), KRAS and EGFR (15% each), and STK11 (serine/threonine kinase 11) (12%). Adenocarcinomas accounted for 89% of all alterations, with TP53 (21%) and KRAS (15%) being most common, while squamous cell carcinomas predominantly harbored TP53 (38%) and MET (15%) mutations. In patients with PD-L1 TPS ≥ 50%, KRAS mutations were enriched (50%), particularly KRAS G12C and G12D, with frequent co-occurrence of TP53 mutations (20%). No pathogenic EGFR mutations were detected in this subgroup. Conclusions: Comprehensive genomic profiling in NSCLC revealed a high prevalence of clinically relevant mutations, with TP53, KRAS and EGFR as the dominant drivers. The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients. Full article

Objective: To evaluate the diagnostic utility of antepartum amnioinfusion in cases of severe oligo- and anhydramnios and to descriptively report perinatal outcomes. Methods: This retrospective single-center study analyzed all antepartum amnioinfusions performed between 2009 and 2024 in pregnancies between 16 + 0 and 34 + 0 weeks of gestation. The primary endpoint was diagnostic impact following amnioinfusion. Secondary endpoints were descriptive perinatal outcomes. No inferential statistical analyses were performed. Results: A total of 37 amnioinfusions were performed in 31 patients. Median gestational age at first amnioinfusion was 22 ± 4.3 weeks, with a mean infusion volume of 259 ± 59.4 mL. The most frequent etiologies were preterm prelabor rupture of membranes (PROM, 29%), fetal growth restriction (FGR, 25.8%), and urogenital malformations (22.6%). Amnioinfusion improved sonographic visualization and diagnostic assessment in the majority of cases. Pregnancy prolongation was observed in selected subgroups; however, causal inference regarding therapeutic efficacy cannot be drawn. Conclusions: Antepartum amnioinfusion represents a valuable adjunct for prenatal diagnostic evaluation in severe oligo- and anhydramnios. Observed perinatal outcomes should be interpreted descriptively. Further prospective, controlled studies are required to define the role of amnioinfusion beyond diagnostic feasibility. Full article

Peters-Plus syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the B3GLCT gene and characterized by multisystem involvement. Fewer than 100 cases have been reported to date, and only a limited number have been diagnosed prenatally. Prenatal identification is challenging due to the variable and non-specific nature of fetal findings and the frequent absence of detectable ocular anomalies during routine ultrasound. We report a prenatal diagnosis of Peters-Plus syndrome in a monochorionic diamniotic twin pregnancy, based on the progressive identification of early-onset intrauterine growth restriction, rhizomelic limb shortening, craniofacial dysmorphism, and mild central nervous system abnormalities. Standard cytogenetic and chromosomal microarray analyses were normal, prompting extended genetic testing. Prenatal exome sequencing identified a homozygous pathogenic splice-site variant (c.660+1G>A) in B3GLCT in both fetuses, confirming the diagnosis. This case highlights the importance of recognizing suggestive multisystem prenatal findings and the crucial role of advanced genetic testing in achieving an accurate prenatal diagnosis. Early molecular confirmation enables appropriate parental counseling regarding prognosis, recurrence risk, and future reproductive options. Full article

Many emerging and re-emerging infectious diseases have been observed over the last few decades around the globe due to population growth, international travel, environmental changes, and microbial adaptation and evolution, despite advances in the medical field. The spread of these diseases is related to complex interactions between pathogens and their hosts. Accordingly, this review summarises current knowledge on infection development and discusses methods used for detection and modeling. Recent studies have revealed the limitations of two-dimensional models and increasingly rely on 3D systems, including spheroids, organoids, and organ-on-a-chip systems, that offer more realistic tissue environments, allowing researchers to more effectively study host–pathogen interactions. Overall, the integration of complementary approaches and the development of 3D models are crucial for enhancing diagnosis, developing new therapeutic approaches, and strengthening control strategies of emerging outbreaks. Full article

Mass spectrometry-based metabolomics is a valuable tool for advancing pediatric health research. Along with nuclear magnetic resonance, it enables detailed biochemical analysis from minimal sample volumes, a critical feature for pediatric diagnosis. Metabolomics supports early detection of inherited metabolic disorders, monitors metabolic changes during growth, and identifies disease markers for a range of conditions, including metabolic, neurodevelopmental, oncological, and infectious diseases. Integrating metabolomic data with genomic, proteomic (i.e., multi-omics approaches), and clinical information enables more precise and preventive care by enhancing risk assessment and informing targeted treatments. However, routine clinical use faces several challenges, including establishing age- and sex-specific reference ranges, standardizing sample collection and processing, ensuring consistency across platforms and laboratories, expanding reference databases, and improving data comparability. Ethical and regulatory issues, including informed consent, data privacy, and equitable access, also require careful consideration. Advances in high-resolution and single-cell metabolomics, artificial intelligence for data analysis, and cost-effective testing are expected to address these barriers and support broader clinical adoption. As standards and data-sharing initiatives grow, metabolomics will play an increasingly important role in pediatric diagnostics and personalized care, enabling earlier disease detection, improved treatment monitoring, and better long-term outcomes for children. Full article

The increasing prevalence of obesity-related primary arterial hypertension (PAH) in the pediatric population emphasizes the need to develop new biomarkers that can aid in clinical practice for prevention or early diagnosis of the cardiovascular disease. The objective of the present study was to evaluate the relationship between selected adipokines, cytokines, and blood pressure (BP) values in children with obesity. A total of 78 children participated in the study: 60 children with obesity (study group) and 18 children with normal weight (control group). Blood pressure was measured according to guidelines. Serum levels of metabolic and inflammatory markers, including leptin, adiponectin, resistin, ghrelin, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α), vascular endothelial growth factor (VEGF), and insulin were determined using multiplex immunoassays. Statistical analysis included correlation and ROC tests to identify potential predictors of PAH. The study group had significantly higher systolic and diastolic BP compared to the control group (p < 0.0001). Serum levels of leptin, IL-6, VEGF, insulin, and resistin were increased in the study group. Leptin, IL-6 and resistin correlated positively with BP values (p < 0.05), while ghrelin and adiponectin correlated negatively. ROC analysis identified leptin, IL-6, and VEGF as the most promising biomarkers for predicting PAH. The results confirm the role of adipokines and cytokines in the pathogenesis of PAH. The assessment of adipokine and cytokine profiles complements traditional anthropometric parameters such as BMI in assessing cardiovascular risk. Leptin, IL-6, and VEGF presented the strongest correlation with hypertension, suggesting their potential in future diagnostic and preventive strategies. Full article

Objective: To investigate the impact of proteinuria severity on obstetric and neonatal outcomes and to assess the predictive value of 24 h urinary protein excretion, both alone and within a multivariable model, for adverse pregnancy outcomes. Methods: This retrospective cohort study included 203 pregnant women with proteinuria who were classified into mild (≥0.3 g/day and <3.0 g/day, n = 50), severe (≥3.0 g/day and <5.0 g/day, n = 67), and massive (≥5.0 g/day; n = 86) groups based on 24 h urine protein levels. Maternal and neonatal outcomes were compared between these groups. Correlation analysis, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression were used to evaluate the predictive value of proteinuria for obstetric complications and identification of increased risk of early delivery. The AUC values of the proteinuria-only model and the multivariable model were compared using the DeLong test, as both models were derived from the same dataset and therefore represented correlated ROC curves. Results: The incidence of obstetric complications was significantly higher in the severe (68.7%) and massive (81.4%) proteinuria groups compared with the mild group (32.0%; p < 0.001). Increasing proteinuria severity was associated with earlier gestational age at delivery, lower birth weight, and higher rates of fetal growth restriction (all p < 0.001). The 24 h proteinuria level demonstrated moderate predictive ability for obstetric complications (AUC 0.73; 95% CI 0.66–0.80). A multivariable model including nephrotic-range proteinuria (≥3 g/day) and gestational age at diagnosis showed improved discriminatory performance compared with proteinuria alone (AUC 0.81; 95% CI 0.75–0.88). The model based on continuous 24 h proteinuria yielded an AUC of 0.73 (95% CI, 0.66–0.80) for identifying pregnancies at increased risk of obstetric complications. The multivariable model showed a numerically higher AUC of 0.81 (95% CI, 0.73–0.86); however, the difference between the two AUCs was not statistically significant according to the DeLong test (z = 0.82, p = 0.41). Conclusions: The severity of maternal proteinuria is associated with a higher likelihood of adverse maternal and neonatal outcomes, and higher proteinuria levels appear to show a graded association with increasing risk. A multivariable model integrating proteinuria with key clinical parameters demonstrated moderate discriminatory ability for obstetric complications, may support a more holistic approach to risk stratification in clinical practice. Full article

The insulin-like growth factor (IGF) axis orchestrates hepatic development, regeneration, and metabolism, yet the roles of individual IGF-binding proteins (IGFBPs) remain incompletely defined. IGFBP-6, a high-affinity, IGF-II-preferring binding protein, has emerged as a context-dependent modulator of IGF bioavailability and cell signaling with additional IGF-independent actions. This review synthesizes current evidence on IGFBP-6 in liver biology and disease. We first outline hepatic expression, regulation, and post-translational processing of IGFBP-6 across development, homeostasis, and injury, and summarize its effects on canonical IGF-II/IGF1R signaling and downstream phosphatidylinositol 3-kinase—protein kinase B (PI3K–AKT) and rat sarcoma—mitogen-activated protein kinase (RAS–MAPK) pathways. We then evaluate experimental and clinical data linking IGFBP-6 to steatotic liver disease, inflammation, and fibrogenesis, including putative roles in hepatocyte stress responses, stellate cell activation, and extracellular matrix remodeling. Finally, we examine IGFBP-6 in primary liver cancers—hepatocellular carcinoma and cholangiocarcinoma—highlighting evidence for tumor-suppressive versus pro-migratory activities, potential crosstalk with hypoxia, Wnt/β-catenin and TGF-β signaling, and interactions with the tumor immune microenvironment. Across conditions, we assess the translational potential of IGFBP-6 as a circulating or tissue biomarker, its utility for patient stratification, and prospects for therapeutic targeting—either by modulating IGF-II sequestration or exploiting IGF-independent mechanisms. We conclude by identifying key knowledge gaps, methodological limitations, and priorities for future studies, including standardized measurement, cell-type-resolved profiling, and in vivo perturbation in clinically relevant models. Collectively, the review positions IGFBP-6 as a nuanced regulator of liver pathophysiology and a promising, yet underexplored, lever for diagnosis and therapy. Full article

Feingold syndrome (FS) is a rare congenital disorder with an autosomal dominant inheritance pattern. Two distinct subtypes are recognized based on their molecular pathology: FS type 1 (FS1) and FS type 2 (FS2). Both types share skeletal anomalies such as microcephaly, brachymesophalangia, and clinodactyly; however, gastrointestinal atresia is unique to FS1. Herein, we report a rare prenatal diagnosis of FS1 in a female fetus. The second-trimester ultrasound revealed bilateral clinodactyly and fetal microcephaly, and the subsequent molecular karyotyping identified a ~342 kb deletion at 2p24.3 encompassing the MYCN gene, confirming the diagnosis. The same deletion was detected in the father, verifying the hereditary pattern. The pregnancy was also complicated by preeclampsia and fetal growth restriction, leading to preterm caesarean delivery at 33 + 3 weeks of gestation. The neonate had microcephaly and clinodactyly but no gastrointestinal defects. In conclusion, high clinical suspicion aroused by identifying ultrasound features of FS can lead to early prenatal diagnosis via molecular karyotyping. Detecting accompanying gastrointestinal disorders that require early operation is crucial for the prognosis, genetic counseling, and prenatal management of the affected families. Full article

Background/Objectives: Combined chromosome 7 gain and chromosome 10 loss (+7/−10) is the most frequent cytogenetic alteration and a defining diagnostic criterion for isocitrate dehydrogenase wild-type (IDHwt) glioblastoma. Despite the association with poor prognosis, its clinical and therapeutic significance remains unclear. We aim to systematically review its clinical significance, focusing on prevalence, prognostic value, and potential association with therapeutic resistance in adult patients. Methods: PubMed, Embase, CENTRAL, Scopus, EBSCOhost, and Web of Science were searched from inception to April 2025, using controlled vocabulary and free-text terms. Eligible studies included adult glioblastoma with molecular confirmation of combined chromosome 7 gain and chromosome 10 loss and reported survival or treatment response. Quality was assessed qualitatively, and findings were synthesized descriptively. Results: Of 3249 records, 5 observational studies (523 patients) were included. The signature was present in 60% to 70% of glioblastoma cases and frequently co-occurred with epidermal growth factor receptor amplification and telomerase reverse transcriptase promoter mutations. This alteration was consistently associated with shorter survival (mean, 8–70 weeks) compared with tumors lacking the alteration (19–170 weeks). In one study, the signature was more common in radioresistant tumors (9/20 vs. 1/10). Molecular evidence suggests that this alteration arises early in tumorigenesis. Conclusions: The +7/−10 cytogenetic alteration, common in glioblastoma, is frequently associated with aggressive clinical behavior. While exploratory data suggest a possible association with radiotherapy response, current evidence is insufficient to establish a predictive or therapeutic role. Its principal clinical value lies in diagnosis, molecular classification, and risk stratification. Incorporating cytogenetic testing for this alteration into routine glioblastoma workup may improve risk stratification and guide individualized management. Full article

Pulpitis is the inflammatory response of the dental pulp to microbial challenge and can range from mild to severe in nature, with severe pulpitis traditionally resulting in pulp removal and root canal treatment (RCT). In the pursuit of more conservative treatments, recent clinical practice guidelines have recommended strategies that preserve the vitality of the dental pulp, rather than RCT, when possible. This has increased the focus on improving the accuracy of pulp diagnosis, which will direct treatment and improve management outcomes. Unfortunately, current point-of-care (PoC) tools are subjective, lack discrimination and rely on the stimulation of pulpal neurons, limiting dentists’ ability to objectively identify the level of inflammation. Molecular biomarker assessment has the potential to dynamically analyse pulpitis and correlate this with inflammatory thresholds and treatment outcomes. Numerous chemokines, cytokines, proteases and growth factors exhibit altered expression during pulpitis and can be collected intraoperatively as part of routine dental treatment. Although current data indicate several markers that could be used as next-generation diagnostic chairside tools for pulpitis, there are currently no commercial kits. Considering the interest in vital pulp treatment, there is an urgent need to engage researchers, industry, dentists and other stakeholders in the development of PoC diagnostic assays for pulpitis. Full article

Background/Objectives: Basal cell carcinoma (BCC) is the most common form of skin cancer, typically exhibiting slow growth and limited metastatic potential. However, in rare, long-standing cases, particularly in high-risk facial regions, deep infiltration into structures such as bone may occur. This study aimed to evaluate whether BCC with bone involvement remains a relevant clinical issue, based on three decades of clinical experience, supplemented by a review of the existing literature. Methods: Medical records of patients treated for facial BCC between 1994 and 2025 at a dermatologic surgery department in Lower Silesia were retrospectively reviewed. Among more than 10,000 cases, eight instances of histologically confirmed bone invasion were identified. Clinical and surgical parameters were analyzed, including patient age, tumor size and location, prior treatment and reconstruction method. Relevant literature was incorporated to provide broader clinical context. Results: Patients with bone-invasive BCC were elderly (mean age: 75.3 years, SD: 10.94 years) and lesions were typically large (mean diameter 38.9 mm), most frequently located on the nose and forehead. Many cases lacked previous treatment. Smaller nasal tumors were managed with local flaps, while larger lesions on the forehead and temple required skin grafts. Findings from the literature confirm that bone invasion is rare and usually associated with long-standing tumors in anatomically high-risk areas. Conclusions: Although rare, BCC with bone infiltration remains a clinically relevant phenomenon, particularly in elderly patients with advanced or recurrent tumors. Early diagnosis, complete excision with histologically clear margins, and individualized surgical planning are essential to prevent deep tissue involvement. Imaging should be reserved for cases in which advanced local invasion is clinically suspected. Full article

Background: To identify the radiomics features of both granulomas and tumorlets (TL) and to assess the potential role of radiomics in differentiating these two diseases. Methods: From 2013 to 2021, ninety patients who had undergone lung surgery and pre-operative chest CT evaluation, with pathologically proven granulomas or TL, were retrospectively enrolled. Two radiologists, in consensus, manually segmented the lesions on CT images. Radiomic features were then automatically extracted from these segmentations using dedicated software. The performance of CT radiomics features in differentiating TL from granulomas was tested by receiver operating characteristic curves and the areas under the curve (AUCs), calculating sensitivity and specificity. Results: The final population consisted of 55 patients (38 female; mean age 64 ± 14 years), 32 with TL and 23 with granulomas. Significant differences were found in 16/107 radiomic features: 3 Shape, 1 First Order, 2 Grey Level Co-occurrence Matrix (GLCM), 2 Gray Level Dependence Matrix (GLDM), 4 Grey Level Run Length Matrix (GLRLM), and 4 Gray Level Size Zone Matrix (GLSZM). Flatness and Long Run High Gray Level Emphasis showed the best performances in discriminating TL from granulomas (AUC: 0.903; sensitivity: 100%; specificity: 80%; and AUC: 0.896; sensitivity: 92.3%; specificity: 76.5%; respectively; both p < 0.001). Conclusions: Radiomics may be a non-invasive imaging tool for characterization of small lung nodules, differentiating granulomas from TL, and may play a role in preventing TL growth and its possible malignant evolution, avoiding delayed diagnosis. Full article

Background and Clinical Significance: The crista terminalis (CT) is a fibromuscular ridge located on the posterolateral wall of the right atrium, formed by the junction of the sinus venosus and the primitive right atrium. A hypertrophic or prominent CT (HCT) refers to a thickened or conspicuous configuration of this normal anatomical structure. In prenatal ultrasound (US) and/or echocardiographic assessments, HCT can mimic a right atrial mass, such as a tumor or a thrombus. Case Presentation: Herein, we describe a case of a fetal right atrial echogenic mass detected at 32 weeks, which remained stable through gestation and was confirmed postnatally as a likely HCT. No hemodynamic compromise, growth, or pathological sequelae were observed. Conclusions: Our case reinforces the importance of including atrial structural variants in the differential diagnosis of intracardiac masses, particularly when features favor stability and low risk. Serial imaging, avoidance of premature invasive measures, and careful counseling are key to appropriate management. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with progressive evolution and high mortality. Magnesium, copper and zinc are essential biometals involved in numerous biological processes in all organs of the human body. A lower level of zinc and magnesium and a higher cooper/zinc ratio are frequently encountered in patients with idiopathic pulmonary fibrosis but also in other forms of pulmonary fibrosis. These imbalances are involved in the main pathogenic mechanisms of idiopathic pulmonary fibrosis: alveolar epithelial cell lesions, oxidative stress, inflammation, fibroblast and myofibroblast proliferation, mitochondrial activity, excessive extracellular matrix accumulation, high collagen production, alveolar macrophage dysfunctions, and apoptosis. A multitude of experimental and clinical studies have shown the importance of these bivalent cations for the synthesis or activity of some important endogenous active substances (fatty acids, eicosanoids, sirtuin1, p53 protein, interleukins, growth factors, some enzymes, and others) involved in one form or another in the pathogenesis of IPF. There are no randomized clinical trials yet, but some clinical and experimental results suggest that the association of zinc and magnesium with pirfenidone and nintedanib could be beneficial and should be assessed as soon as possible after the onset of this disease. The correction of hypomagnesemia and hypozincemia, whenever they exist, must be performed as soon as possible after the diagnosis of fibrosis. Full article