Search Results (45,629)

Background and Objectives: Chronic kidney disease (CKD) is associated with severe coronary calcification and increased procedural risks. We aimed to evaluate the impact of CKD on contrast-induced nephropathy (CIN), bleeding, and clinical outcomes in patients undergoing rotational atherectomy (RA). Materials and Methods: This study retrospectively analyzed 652 patients who underwent RA for calcified coronary lesions from the multicenter ROCK registry and a single-center extension between 2010 and 2025. Patients were classified into CKD (eGFR < 60 mL/min/1.73 m², n = 66) and non-CKD (n = 586) groups, excluding those on dialysis. The primary endpoint was a composite of CIN and in-hospital bleeding. Secondary endpoints included 3-year target vessel failure (TVF), myocardial infarction (MI), and total bleeding. Results: The primary composite outcome occurred more frequently in the CKD group (16.7% vs. 5.1%, p = 0.001). Specifically, CIN was significantly higher in CKD patients (15.2% vs. 1.7%, p < 0.001), while in-hospital bleeding did not differ significantly. In multivariate analysis, CKD was an independent predictor of the primary outcome (adjusted OR 3.02; 95% CI 1.36–6.69; p = 0.006). At 3-year follow-up, total bleeding (10.6% vs. 3.9%, p = 0.008) and MI (6.1% vs. 2.1%, p = 0.024) were higher in the CKD group, whereas TVF and cardiac death showed no significant difference. Conclusions: CKD is a robust independent risk factor for CIN and long-term bleeding in patients undergoing RA. However, comparable clinical efficacy outcomes suggest that RA remains a feasible strategy in CKD patients when early complications are carefully managed with contrast-minimizing strategies. Full article

Background and Objectives: Although carotid endarterectomy (CEA) is the gold standard in the treatment of carotid disease, a higher frequency of adverse outcomes can reduce its benefit. The aim of the present study is to identify factors related to myocardial infarction, stroke, death and restenosis as the late adverse outcomes of CEA. Materials and Methods: The retrospective cohort study included 1597 CEAs that were performed in 1533 consecutive patients at the Vascular Surgery Clinic in Belgrade from 2012 to 2017. Late adverse outcomes within 4 years after CEA were available for the majority of them. Data for myocardial infarction and stroke were available for 1223 CEAs, data for death for 1305 CEAs, and data for restenosis for 1162 CEAs. The association between possible risk factors and late adverse outcomes of CEA was analyzed using univariate and multivariate Cox and logistic regression analyses. Results: During follow-up, myocardial infarction occurred after 55, stroke after 68, death after 103 and restenosis after 121 CEAs. Two factors were the most frequent predictors of late adverse outcomes, i.e., the patient’s age and diabetes mellitus (DM). Age predicted all late adverse outcomes except restenosis, and DM predicted all of them. A predictor of myocardial infarction, besides age (HR 1.08, 95% CI 1.05–1.11) and DM (HR 1.60, 95% CI 1.11–2.29), was peripheral arterial disease (HR 1.81, 95% CI 1.17–2.78) in personal history. Predictors were only age (HR 1.04, 95% CI 1.01–1.08) and DM (HR 1.68, 95% CI 1.03–2.72) for stroke, as well as for death (HR 1.17, 95% CI 1.12–1.21 and HR 1.94, 95% CI 1.17–3.21, respectively). For restenosis, in addition to DM (HR 1.78, 95% CI 2.62), predictors were hyperlipidemia (HR 3.52, 95% CI 1.27–9.76) and urgent surgery (HR 3.51, 95% CI 1.06–11.65). Conclusions: CEA should be performed with special caution in the elderly and diabetic patients. Modification of other risk factors and precise medical therapy are necessary to reduce possible adverse outcomes. Full article

Background: Hypoxic–ischemic encephalopathy (HIE) remains a major cause of neonatal mortality and long-term neurodevelopmental impairment despite advances in perinatal care and the widespread use of therapeutic hypothermia. Reliable early prognostic markers are essential for risk stratification and long-term follow-up planning. This study aimed to evaluate long-term neurodevelopmental outcomes and associated prognostic factors in neonates with HIE treated in the era of therapeutic hypothermia. Methods: This retrospective cohort study was conducted in a tertiary neonatal intensive care unit between January 2020 and June 2024. Neonates with gestational age ≥ 35 weeks diagnosed with HIE were included. Clinical characteristics, laboratory parameters, neurophysiological findings, neuroimaging results, and indicators of multiorgan dysfunction were recorded. Long-term neurodevelopmental outcomes were assessed at 18 to 24 months of age. The primary outcome was death or severe neurodevelopmental impairment. Multivariable logistic regression analysis was performed to identify independent predictors of adverse outcomes. Results: A total of 99 neonates were included. Therapeutic hypothermia was administered to 86 (86.9%) infants. Severe neurodevelopmental impairment or death occurred in 18 (18.2%) patients. Cerebral palsy was diagnosed in 19 (20.9%) survivors, developmental delay in 12 (13.2%), epilepsy in 16 (17.6%), and feeding difficulties in 9 (9.9%). In multivariable analysis, higher lactate levels (adjusted OR = 1.239, 95% CI = 1.052–1.458), lower Apgar score at 5 min (adjusted OR = 0.570, 95% CI = 0.344–0.944), and renal dysfunction (adjusted OR = 7.947, 95% CI = 2.027–31.164) were independently associated with severe neurodevelopmental impairment or death. Multiorgan dysfunction and abnormal neurophysiological and neuroimaging findings were significantly associated with adverse outcomes. Conclusions: Early biochemical markers, neurological assessments, neurophysiological recordings, neuroimaging patterns, and systemic organ dysfunction are closely associated with long-term neurodevelopmental outcomes in neonates with HIE. A multidimensional approach to early prognostic evaluation may improve risk stratification and guide targeted follow-up and intervention strategies. Full article

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer-related deaths. While intestinal microbiota dysbiosis is linked to CRC, the direct role of intratumoral bacteria in metastasis remains poorly understood. In this study, we isolated pathogenic bacteria from CRC tumor tissues, identified as Hungatella hathewayi (H. hathewayi), through the 16S rRNA gene and whole-genome sequencing. We developed specific primers (P48/P52) and polyclonal antibodies for detecting H. hathewayi in samples. Using quantitative real-time PCR (qPCR), we found significant enrichment of H. hathewayi in fecal samples from CRC patients compared to healthy controls, with mean fold changes of 137-fold and 142-fold for primers P48 and P52, respectively. Analysis of tissue samples revealed that H. hathewayi abundance was higher in CRC tumor tissues compared to normal tissues, with mean fold changes of 2.90 for P48 and 3.97 for P52. Fluorescence in situ hybridization (FISH), immunofluorescence (IF), and immunohistochemistry (IHC) confirmed its spatial distribution within tumor tissues. In vitro assays using CRC cell lines demonstrated that H. hathewayi-derived succinate upregulates HIF-1α and SUCNR1 expression and promotes cell metastasis by inducing epithelial–mesenchymal transition (EMT). Collectively, these findings identify H. hathewayi as a novel pro-metastatic bacterium and a potential non-invasive biomarker for CRC diagnosis, providing direct evidence for the role of intratumoral bacteria in CRC progression. Full article

The term asphyxia refers to a disruption in brain function due to rapid and persistent cerebral hypoxia or anoxia as a consequence of accidental or non-accidental injury. Considering the different mechanisms that may determine asphyxiation, such injuries can be referred to different categories: strangulation (death by hanging, ligature or manual strangulation), suffocation (smothering, choking, confined spaces and vitiated atmosphere), mechanical asphyxia (positional and traumatic asphyxia) and drowning (submersion or immersion in liquid). In both human and veterinary forensic practice, fatal asphyxia is considered among the most diagnostically challenging categories of sudden death, as it often produces only subtle and non-pathognomonic macroscopic signs, which can be easily covered by post-mortem alterations. Therefore, a wide range of information is often needed for the diagnosis of asphyxiation, including medical history, crime scene analysis, testimonies and physical evidence, along with the macroscopic and histological findings. The following review addresses the main lesions, ancillary tests and diagnostic issues associated with non-drowning asphyxia in veterinary forensic pathology. Full article

Background: Immune checkpoint inhibitors (ICIs) have become the standard first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression. However, the optimal selection between immunotherapy monotherapy and chemo-immunotherapy in patients with a PD-L1 tumor proportion score (TPS) ≥ 50% remains uncertain in routine clinical practice. Methods: We retrospectively reviewed patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% who initiated first-line treatment with pembrolizumab monotherapy or pembrolizumab combined with platinum-based chemotherapy at the Istanbul Medipol University Department of Medical Oncology between July 2017 and December 2024. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated and compared according to PD-L1 expression levels and treatment strategy. Prognostic factors associated with survival outcomes were also explored. Results: A total of 65 patients were included, of whom 36 received pembrolizumab plus chemotherapy and 29 received pembrolizumab monotherapy. The estimated median PFS and OS for the entire cohort were 24.2 months (95% CI, 6.5–33.0) and 34.6 months (95% CI, 6.5–62.7), respectively. Patients with very high PD-L1 expression (TPS ≥ 90%) experienced significantly longer survival outcomes compared with those with a TPS of 50–89%, and a PD-L1 TPS ≥ 90% remained an independent prognostic factor for OS. When treatment strategies were compared across the entire cohort, no statistically significant differences in PFS or OS were observed between immunotherapy monotherapy and chemo-immunotherapy. Hypertension was identified as an independent negative prognostic factor for PFS. In patients with a PD-L1 TPS ≥ 90%, survival outcomes numerically favored pembrolizumab monotherapy, although this difference did not reach statistical significance. Conclusions: In this real-world cohort of patients with PD-L1 high metastatic NSCLC, PD-L1 expression, particularly very high TPS levels, was strongly associated with survival outcomes. While no survival differences were observed between treatment strategies in the overall population, pembrolizumab monotherapy may represent an appropriate first-line option in selected patients with a PD-L1 TPS ≥ 90%. Larger prospective studies are warranted to refine treatment selection in this setting. Full article

Background/Objectives: Non-thyroidal illness syndrome (NTIS) also known as low FT3 syndrome is characterized by altered thyroid hormone levels during severe illness, is common in end-stage renal disease, and reflects metabolic and inflammatory stress. This study evaluated the thyroid hormone profiles of patients undergoing maintenance hemodialysis, assessing relationships between NTIS severity and dialysis adequacy while accounting for mineral and bone metabolism markers, anemia status, duration of dialysis therapy, and their association with the number of deaths during follow-up. Methods: This prospective bi-center study included adults receiving maintenance hemodialysis for at least 3 months. Patients treated for thyroid disease or taking medications affecting the hypothalamus–pituitary–thyroid axis were excluded. Thyroid-stimulating hormone, free triiodothyronine (fT3), and free thyroxine (fT4) levels were measured, and dialysis adequacy was assessed using spKt/V. Patients were classified as euthyroid or having NTIS (stratified by severity), and associations between clinical characteristics and the number of deceased patients during a 6-month observation period were analyzed using receiver operating characteristic (ROC) curves to determine prognostic cut-off values for thyroid hormones. Results: Among 74 patients, 50% had NTIS and exhibited significantly lower dialysis adequacy than euthyroid individuals (median spKt/V 1.0 vs. 1.1; p = 0.03), with spKt/V declining as NTIS severity increased (stages I–III, p = 0.008). NTIS severity correlated with age and pulmonary comorbidities, while mineral and bone metabolism markers were comparable between the groups. During the 6-month follow-up, 23% of the patients died, exhibiting significantly lower fT3 and fT4 levels than survivors. ROC analysis identified clinically relevant fT3 and fT4 cut-off values that were associated with the number of deaths. Conclusions: NTIS in hemodialysis patients correlates with reduced dialysis adequacy and appears to be a prognostic factor for risk of death. NTIS severity correlated with declining spKt/V, potentially reflecting disease burden, and thyroid hormone assessment may provide prognostic information. Full article

Background: Fumonisin B1 (FB1) is a toxic secondary metabolite produced by Fusarium species that commonly contaminates cereal crops, posing serious threats to crop productivity and food safety. In plants, FB1 inhibits ceramide synthase, disrupts sphingolipid metabolism, and induces growth inhibition and programmed cell death. Despite the agricultural importance of fumonisin contamination, genetic strategies to enhance FB1 tolerance or detoxification capacity in crops remain limited, largely due to an incomplete understanding of the underlying genetic determinants. Methods: To identify genetic determinants associated with FB1 tolerance, we exploited natural variation in Arabidopsis thaliana and conducted a genome-wide association study (GWAS). Candidate genes were further examined using gene expression analyses and functional characterization of overexpression and SALK mutant lines. Results: GWAS revealed a significant association locus on chromosome 1 linked to FB1 tolerance. Two adjacent genes within this locus, AT1G14750 and AT1G14755, were identified as positive regulators of FB1 tolerance. Both genes were rapidly induced upon FB1 exposure. Functional analyses demonstrated that overexpression of either gene significantly enhanced tolerance to FB1-induced damage, whereas SALK mutant lines displayed increased sensitivity, manifested by enhanced growth inhibition and necrosis. Conclusions: Our study identifies AT1G14750 and AT1G14755 as previously uncharacterized components of FB1 tolerance in Arabidopsis. These findings provide new insights into the genetic architecture of plant response to mycotoxin stress and establish a foundation for further studies on the molecular mechanisms underlying FB1 tolerance. Full article

Type 2 diabetes mellitus is associated with major cardiovascular complications, including cardiac autonomic neuropathy, which contributes to sympathetic–parasympathetic imbalance and increases susceptibility to arrhythmias and sudden cardiac death. Heart rate variability, assessed through R–R intervals on electrocardiography and 24 h Holter monitoring, represents a sensitive, non-invasive marker of autonomic dysfunction and arrhythmogenic risk. In patients with type 2 diabetes mellitus, chronic hyperglycaemia, oxidative stress, and metabolic inflammation lead to early impairment of the autonomic nervous system, manifested by consistent reductions in SDNN, RMSSD, pNN50, total power, and the high-frequency component, indicating diminished parasympathetic tone and sympathetic predominance. Nonlinear HRV indices demonstrate a loss of complexity and fractal organisation, providing additional prognostic value beyond conventional time- and frequency-domain analyses. Reduced HRV correlates with the severity of cardiac autonomic neuropathy, duration of diabetes, and poor glycaemic control, identifying patients with increased arrhythmogenic vulnerability. HRV analysis enables prediction of arrhythmic risk, facilitating the identification of high-risk individuals and guiding personalised interventions. The integration of HRV assessment into routine clinical practice may improve the early detection of subclinical autonomic neuropathy and optimise cardiovascular risk stratification and management in patients with type 2 diabetes mellitus. Full article

Malaria remains a major global health burden, with an estimated 282 million cases and 610,000 deaths reported in 2024, disproportionately affecting children under five years of age and pregnant women in sub-Saharan Africa. Although antimalarial drugs are highly effective at clearing infections, their reliance on timely diagnosis and treatment limits their scalability as a population-wide control strategy. Vaccines therefore represent a critical tool for reducing malaria-associated morbidity and mortality, as well as interrupting parasite transmission, by inducing durable protective immunity. However, the complex lifecycle of Plasmodium parasites poses significant challenges for vaccine development, including the identification of protective antigens and optimal vaccine formulations. In this review, we summarize current vaccine strategies and discuss their key limitations. We also highlight emerging opportunities for possible avenues for future research and development. Full article

Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a natural flavonoid isolated from Epimedium brevicornu Maxim., against C. irritans. In vitro exposure to baohuoside I suppressed theront viability and tomont hatching in a dose- and time-dependent manner, inducing an apoptosis-like death in both stages, characterized by ciliary detachment, mitochondrial disruption, nuclear condensation, and extensive vacuolization, as evidenced by transmission electron microscopy and Annexin V-FITC/PI staining. Further studies demonstrated that baohuoside I elevated the intracellular Ca²⁺ and reactive oxygen species levels in tomonts, indicating Ca²⁺ overload and oxidative stress. Transcriptomic analysis of infected Larimichthys crocea skin revealed that baohuoside I upregulated immune-related genes while downregulating pro-inflammatory genes, concurrently enhancing host serum acid phosphatase activity and mitigating oxidative stress in enzyme activity assays. In vivo trials showed that oral administration of baohuoside I reduced trophont attachment and improved fish survival. It did not exhibit hemolytic activity at concentrations effective against the parasites. Collectively, these findings elucidate a multi-target mechanism of baohuoside I, highlighting its potential as an eco-friendly therapeutic agent for cryptocaryoniasis control in marine aquaculture. Full article

Precision in radiotherapy requires the development of standardized, reproducible, and biologically relevant models to accurately assess the efficacy and safety of various radiobiological sources. This review presents a novel approach using precision-cut organotypic tissue slices (OTSs), or organotypic tissue cultures (OTCs), as a representative model with potential for unifying the assessment of radiobiological sources. Derived from specific organs, OTSs retain the complex architecture and multicellular environment of the tissue, providing a unique platform that bridges the gap between in vitro cell cultures and in vivo animal models. The typed OTSs can effectively mimic the in vivo physiological responses to ionizing radiation, providing insight into the mechanisms of radiation-induced damage and repair, and the potential for radiation-induced toxicity and side effects. The emerging practices for the use of OTSs in radiobiological studies include slice mechanical preparation, radiation exposure, and outcomes assessment. The prepared approach for OTS preparation promises to improve the reliability and comparability of radiobiological studies, facilitating the development of safer and more effective radiation therapies. OTSs have the potential to significantly advance our understanding and application of radiation medicine and research by providing a physiologically relevant assessment of radiobiological effects of novel ionizing radiation sources. Full article

Background: Medical Assistance in Dying (MAiD) was first legalized in Canada in 2016, with legislation expanding from foreseeable to non-foreseeable natural deaths. A sole underlying medical condition of mental illness is expected to be added in 2027. Although legislation and reporting requirements are federally mandated, the implementation and delivery of MAiD are the responsibility of individual provinces and territories. Objectives: The aim of this study is to compare the organization, delivery, and oversight of MAiD programs across provinces and territories in consideration of access, equity, and safeguards. Methods: This study used a mixed methods approach to collect data. A comprehensive and systematic search for published peer reviewed literature on MAiD programs in Canada was conducted along with qualitative interviews with key informants using purposive and snowball sampling. A qualitative descriptive design was used for qualitative data, including content analysis. To facilitate a detailed comparative analysis of MAiD across jurisdictions, separate tables were created for each component or element, organizing the results of the literature review and qualitative analysis by jurisdiction. Patterns within these tables were identified through qualitative interpretation. The findings were then summarized in a narrative format. Results: A total of 113 interviews were conducted, representing all provinces and territories but Nunavut. Findings showed varied practices throughout the MAiD process between jurisdictions. Conclusions: The main findings of this study are that the organization of MAiD programs, oversight, reporting methods to Health Canada, intake, preliminary assessments, assessments, provision, and bereavement support vary. In addition, specific policies related to potentially vulnerable populations are lacking and jurisdictional practices also vary. Centralized, multidisciplinary MAiD programs with strong oversight mechanisms may strengthen issues related to access, equity, and safeguards. Full article

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for more deaths than any other malignancy. Despite advances in treatment, it remains highly lethal, with 5-year survival rates showing minimal improvement over the past several decades, highlighting a critical unmet clinical need. Macrophage Migration Inhibitory Factor (MIF) is a multifunctional cytokine that contributes to inflammation and cancer, promoting tumor growth, progression, and metastasis through modulation of the tumor microenvironment, stimulation of angiogenesis, and regulation of immune responses. Polymorphisms in the promoter region of MIF, such as high-expression CATT repeats, influence MIF expression and susceptibility to a range of inflammatory, autoimmune, and malignant disorders, yet their role in lung cancer remains largely unexplored. Therapeutic strategies targeting MIF, including small-molecule inhibitors, antibodies, and peptide-based agents, have shown promise in preclinical models, although their clinical translation is still limited. This review discusses the dual role of MIF in inflammation and oncology, summarizes current therapeutic developments, and emphasizes the potential of MIF-targeted interventions in lung cancer. It discusses the significance of genetic predisposition, particularly high-expression MIF alleles, in guiding personalized treatment strategies for lung cancer and identifying patients who may derive benefit from MIF inhibition. Full article

Background: The combination of conventional drugs and inhibitors of signaling molecules is an effective strategy to increase cancer treatment efficacy and reduce drug doses to protect against their cytotoxic effects. Our research has shown the cisplatin concentration-dependent shift in the role of MAP kinase JNK from antiapoptotic to proapoptotic in non-small cell lung cancer A549 cells. Cell death/survival signaling molecules, tumor suppressor p53 and pro-survival protein kinase AKT were detected to be differently regulated by JNK inhibition at low vs. high cisplatin concentrations. Here, we further investigated the phenomenon and potential mechanisms of combined JNK inhibition and cisplatin treatment. Methods: Cell death in vitro was evaluated by MTT and Western blot assays after combined cisplatin and specific inhibitor treatment; two-way ANOVA was used for analysis. Results: JNK is differently involved in determining cellular sensitivity to different DNA-damaging drugs. There is no universal cell death induction mechanism originating from DNA damage through the involvement of JNK. The outcome of JNK inhibition also depends on the cell type. We found that there is an unusual reciprocal interaction between p53 and AKT in cisplatin-treated A549 cells, where p53 inhibits AKT, while AKT activates p53. In the case of cisplatin + JNK inhibitor SP600125, DNA damage and reactive oxygen species (ROS) contribute to cell death regulation in different ways. ROS exert opposite roles on cell fate-determining molecules p53 and AKT, and ROS act on p53 and AKT in opposite directions at low vs. high concentrations of cisplatin, combined or not with JNK inhibition. The differentially activated p53 in response to ROS (at low versus high concentrations of cisplatin, combined with JNK inhibitor) may be a molecular switch in the role of JNK from antiapoptotic to neutral/proapoptotic, and an executor of cell death. ROS is a possible threshold regulator that, together with an as-yet-unidentified factor, can differentially regulate p53. As a result, AKT phosphorylation and function are altered. The findings emphasize the importance of assessing the role of drug concentration when combining them with JNK inhibition when monitoring therapeutic efficacy and toxicity issues in personalized cancer treatment. Full article