Search Results (855)

Background: While most Escherichia coli strains are harmless members of the gastrointestinal microbiota, certain pathogenic variants can cause severe intestinal and extraintestinal diseases. A notable outbreak of E. coli O104:H4, involving both enteroaggregative (EAEC) and enterohemorrhagic (EHEC) strains, occurred in Europe, resulting in symptoms ranging from bloody diarrhea to life-threatening colitis and hemolytic uremic syndrome (HUS). Since treatment options remain limited and have changed little over the past 40 years, there is an urgent need for an effective vaccine. Such a vaccine would offer major public health and economic benefits by preventing severe infections and reducing outbreak-related costs. A multiepitope vaccine approach, enabled by advances in immunoinformatics, offers a promising strategy for targeting HUS-causing E. coli (O104:H4 and O157:H7 serotypes) with minimal disruption to normal microbiota. This study aimed to design an immunogenic multiepitope vaccine (MEV) construct using bioinformatics and immunoinformatic tools. Methods and Results: Comparative proteomic analysis identified 672 proteins unique to E. coli O104:H4, excluding proteins shared with the nonpathogenic E. coli K-12-MG1655 strain and those shorter than 100 amino acids. Subcellular localization (P-SORTb) identified 17 extracellular or outer membrane proteins. Four proteins were selected as vaccine candidates based on transmembrane domains (TMHMM), antigenicity (VaxiJen), and conservation among EHEC strains. Epitope prediction revealed ten B-cell, four cytotoxic T-cell, and three helper T-cell epitopes. Four MEVs with different adjuvants were designed and assessed for solubility, stability, and antigenicity. Structural refinement (GALAXY) and docking studies confirmed strong interaction with Toll-Like Receptor 4 (TLR4). In silico immune simulations (C-ImmSim) indicated robust humoral and cellular immune responses. In Conclusions, the proposed MEV construct demonstrated promising immunogenicity and warrants further validation in experimental models. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article

Introduction: In healthcare centers with limited resources, or for patients who prefer to make continuous changes in their treatment themselves and do not want to rely solely on technology, intermittent glucose monitoring (isCGM) with an insulin pump is a viable option that warrants further study. Material and methods: prospective single-center study that collected data at 3 months and after isCGM implantation in pediatric patients with Type 1 diabetes, categorized according to their insulin regimen. Results: We found statistically significant differences in the time in range (TIR) between 70 and 180 mg/dl at 3 months after using the sensor (p = 0.017), although these differences were not maintained at 1 year (p = 0.064). When stricter TIRs (70–140 mg/dl) were analyzed, statistically significant differences were observed at 3 months (p = 0.01) and at 1 year (p = 0.018) in favor of patients using CSII. While 75% of the patients in the CSII group had good control with HbA1c < 7% after one year of sensor use, only 34.6% in the MDI group achieved these values. However, the CSII group presented a higher coefficient of variation (62.31% at 3 months and 43.08% at 1 year) (p = 0.02), and a higher number of hypoglycemic episodes (7.38% and 7.32%, respectively) (p = 0.016). The CSII group also had a higher number of capillary blood glucose measurements at the beginning of the study (8.32/day) (p = 0.249), but this number became similar between both groups after one year. Conclusions: We found statistically significant differences in favor of CSII over MDI in terms of metabolic control after one year of isCGM use. However, the TIR values were still below the range considered to be indicative of good control. These findings lead us to question whether CSII should be initially considered in specific cases where HCL is not possible, or if it would be more effective to wait until the patient is ready, or the necessary resources are available to start directly CSII integrated in a closed loop system. Full article

Objective: Dysphagia is common among elderly patients after hip fracture surgery and can lead to aspiration pneumonia, malnutrition, and delayed rehabilitation. This study aims to present current clinical practice patterns of assessment and intervention for dysphagia in this patient group. Methods: The study was conducted through a two-round online questionnaire targeting Danish occupational therapists with expertise in dysphagia post hip fracture. Results: A total of 71 therapists participated in round one, and 44 (62%) completed round two. Triggers for assessment included coughing, recurrent pneumonia, voice changes, altered eating habits, unplanned weight loss, functional decline, and comorbidities; age was rarely used. Frequently used assessment tools were Facio-Oral Tract Therapy (57.1%), the Minimal Eating Observation Form—Version II (40%) and the Volume–Viscosity Swallow Test (41.4%). Key interventions included texture modification, posture correction, patient education, oral hygiene optimization, compensatory strategies, and dysphagia training; oral screens and electrical stimulation were less common. Conclusions: This study provides a descriptive overview of current dysphagia assessment triggers, tools, and interventions used for elderly hip fracture patients in Denmark. The findings highlight clinical practice patterns that can inform future research on patient outcomes and the effectiveness of specific interventions in this population. Full article

Background: The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a profound impact on global health, extending beyond pulmonary complications. Cardiovascular involvement in COVID-19 is multifactorial and may be influenced by viral load, inflammatory response, and pre-existing comorbidities. Discussion: Acute complications include myocardial injury, arrhythmias, acute coronary syndromes (ACS), heart failure, Takotsubo cardiomyopathy, myopericarditis, and cardiac arrest. Notably, atrial fibrillation (AF) emerges as a frequent arrhythmic complication, particularly among critically ill patients, and is associated with increased mortality. COVID-19-patients with concomitant ACS present more severe clinical profiles and higher rates of thrombotic events, including stent thrombosis. Cardiac arrest predominantly presents with non-shockable rhythms and is associated with dismal outcomes. COVID-19 also exacerbates heart failure, both by aggravating existing cardiac dysfunction or by precipitating de novo heart failure. Takotsubo cardiomyopathy and myocarditis, although less frequent, have been reported and are often underdiagnosed due to subtle clinical presentations. Right ventricular dysfunction, linked to pulmonary involvement, has emerged as a key prognostic marker. Post-COVID-19 syndrome include persistent cardiac abnormalities such as reduced ventricular function and myocardial inflammation. Cardiac magnetic resonance imaging and strain echocardiography have proven useful in identifying subclinical cardiac involvement. Conclusions: Early recognition and monitoring of cardiovascular complications are crucial for improving outcomes in patients affected by COVID-19. This review summarizes current evidence regarding cardiovascular manifestations associated with COVID-19. Full article

Critical illness profoundly disrupts the gut microbiota leading to a state of dysbiosis characterized by reduced microbial diversity and overrepresentation of pathogenic taxa such as Enterobacteriaceae and Proteobacteria. This dysbiotic shift compromises gut barrier integrity and modulates immune responses, contributing to systemic inflammation and increasing susceptibility to nosocomial infections and multi-organ dysfunction. Nutritional strategies in the ICU significantly influence the composition and function of the gut microbiota. Enteral nutrition supports the maintenance of microbial diversity and gut mucosal health, whereas parenteral nutrition is associated with mucosal atrophy and further microbial imbalance. Emerging interventions, including the administration of probiotics, prebiotics, synbiotics, and fermented products like kefir, show promise in restoring microbial equilibrium and improving patient outcomes. This review presents current evidence on the alterations of the gut microbiota in critically ill patients, explores the systemic consequences of dysbiosis, and evaluates the impact of nutritional and microbiota-targeted therapies in improving patient outcomes. Full article

With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of hypoglycaemia, dementia and hospitalisation. Therefore, regular screening for all aspects of frailty should be an integrated part of the care plans of older people with diabetes. In addition, every effort should be made for prevention, which includes adequate nutrition combined with regular resistance exercise training. In already frail older people with diabetes, metabolic targets should be relaxed and hypoglycaemic agents should be of low hypoglycaemic risk potential. Furthermore, the metabolic phenotype of frailty should be considered when choosing hypoglycaemic agents and determining targets. With increasing severity of frailty, proactive chronological plans of de-escalation, palliation and end-of-life care should be considered. These plans should be undertaken in a shared decision-making manner which involves patients and their families. This ensures that patients’ views, wishes and preferences are in the heart of these plans. Full article

Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects as expression quantitative trait loci (eQTLs) across six physiologically relevant tissues: peripheral blood, sigmoid colon, ileum, ovary, uterus, and vagina. Methods. GWAS-identified variants were cross-referenced with tissue-specific eQTL data from the GTEx v8 database. We prioritized genes either frequently regulated by eQTLs or showing the strongest regulatory effects (based on slope values, which indicate the direction and magnitude of the effect on gene expression). Functional interpretation was performed using MSigDB Hallmark gene sets and Cancer Hallmarks gene collections. Results. A tissue specificity was observed in the regulatory profiles of eQTL-associated genes. In the colon, ileum, and peripheral blood, immune and epithelial signaling genes predominated. In contrast, reproductive tissues showed the enrichment of genes involved in hormonal response, tissue remodeling, and adhesion. Key regulators such as MICB, CLDN23, and GATA4 were consistently linked to hallmark pathways, including immune evasion, angiogenesis, and proliferative signaling. Notably, a substantial subset of regulated genes was not associated with any known pathway, indicating potential novel regulatory mechanisms. Conclusions. This integrative approach highlights the com-plexity of tissue-specific gene regulation mediated by endometriosis-associated variants. Our findings provide a functional framework to prioritize candidate genes and support new mechanistic hypotheses for the molecular pathophysiology of endometriosis. Full article

Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and clinical comorbidities. We queried the United States Renal Data System for ESRD patients starting dialysis between 1 January 2005 and 31 December 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Methods: Cox proportional hazards models were used to assess mortality, adjusting for demographic and clinical factors. Results: Among 1,155,136 patients, increased age [adjusted odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94–0.96]; black race (OR = 0.67, CI: 0.51–0.89); and Hispanic ethnicity (OR = 0.43, CI: 0.28–0.66) were associated with a lower risk of TPE-treated TTP diagnosis, whereas female sex (OR = 1.59, CI: 1.25–2.02) and tobacco use (OR = 2.08, CI: 1.58–2.75) had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021–0.028). Female sex, black race, Hispanic ethnicity, and hypothyroidism were also associated with decreased all-cause mortality. Conclusions: These findings suggest that ESRD patients with TPE-treated TTP are significantly protected from mortality compared with ESRD patients without this diagnosis. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Introduction: Ocular complications associated with dental procedures are diverse but have been primarily reported through case reports and series, with no comprehensive reviews to date. The underlying mechanisms of these complications are often poorly understood by medical professionals, partly due to limited interdisciplinary education. This review aims to bridge this gap by summarizing the relevant anatomical connections between the oral and ocular regions, exploring the mechanisms through which dental procedures may lead to ophthalmic complications, and detailing their clinical presentations, progression, and potential management and preventive strategies. Methods: Published case reports and case series from 1950 to October 2024 that described ophthalmic complications in human patients following dental procedures were included in this scoping review. Results: Dental procedures can give rise to a variety of ophthalmological complications, whether neuro–ophthalmic (e.g., diplopia, ptosis, or vision loss), vascular (e.g., retrobulbar hemorrhage or cervical artery dissection), infectious (e.g., orbital cellulitis or abscess), mechanical (e.g., orbital trauma or fractures), or air-related (e.g., orbital and subcutaneous emphysema). Conclusions: Most of the ophthalmological complications following dental procedures are often reversible, but some can be vision-threatening or lead to permanent sequelae if not promptly recognized and managed. Prevention through precise technique and anatomical awareness, early identification of symptoms, and timely multidisciplinary collaboration are crucial to minimizing risks and ensuring better patient outcomes. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Background: Computed tomography urography (CTU) is routinely used to evaluate the upper urinary tract in patients with hematuria. CTU may detect incidental findings outside the urinary tract, but it remains unclear if this adds value. This study aimed to develop a deep learning algorithm that automatically segments and selectively visualizes the urinary tract on CTU. Methods: The urinary tract (kidneys, ureters, and urinary bladder) was manually segmented on 2 mm dual-phase CTU slices of 111 subjects. With this dataset, a deep learning-based AI was trained to automatically segment and selectively visualize the urinary tract on CTU scans (including accompanying unenhanced CT scans), which we dub “focused view CTU”. Focused view CTU was technically optimized and tested in 39 subjects with hematuria. Results: The technically optimized focused view CTU algorithm provided complete visualization of 97.4% of kidneys, 80.8% of ureters, and 94.9% of urinary bladders. All urinary tract organs were completely visualized in 66.6% of cases. In these cases (excluding 33.3% of cases with incomplete visualization), focused view CTU intrinsically achieved a sensitivity, specificity, positive predictive value, and negative predictive value of 100.0%, 92.3%, 92.9%, and 100.0% for lesions in the urinary tract compared to unmodified CT, although interrater agreement was moderate (κ = 0.528). All incidental findings were successfully hidden by focused view CTU. Conclusions: Focused view CTU provides adequate urinary tract segmentation in most cases, but further research is needed to optimize the technique (segmentation does not succeed in about one-third of cases). It offers selective urinary tract visualization, potentially aiding in assessing relevance and cost-effectiveness of detecting incidental findings in hematuria patients through a prospective randomized trial. Full article

Background: Non-communicable diseases (NCDs) are a leading cause of mortality globally, contributing significantly to the burden on healthcare systems. Understanding the spatiotemporal patterns of NCD mortality is crucial for identifying vulnerable populations and regions at high risk. Objectives: Here, we evaluated the spatiotemporal patterns of NCD mortality in the Metropolitan Area of the Valley of Mexico (MAVM) from 2000 to 2019 for five International Classification of Diseases chapters (4, 5, 6, 9, and 10) at two spatial scales: the municipal level and metropolitan region. Methods: Mortality rates were calculated for the total population and stratified by sex and age groups at both spatial scales. In addition, the relative risk (RR) of mortality was estimated to identify vulnerable population groups and regions with a high risk of mortality, using women and the 25–34 age group as reference categories for population-level analysis, and the overall MAVM mortality rate as the reference for municipal-level analysis. Results: Mortality trends showed that circulatory-system diseases (Chapter 9) are emerging as a concerning health issue, with 45 municipalities showing increasing mortality trends, especially among older adults. Respiratory-system diseases (Chapter 10), mental and behavioral disorders (Chapter 5) and nervous-system diseases (Chapter 6) predominantly did not exhibit a consistent general mortality trend. However, upon disaggregating by sex and age groups, specific negative or positive trends emerged at the municipal level for some of these chapters or subgroups. Endocrine, nutritional, and metabolic diseases (Chapter 4) showed a complex pattern, with some age groups presenting increasing mortality trends, and 52 municipalities showing increasing trends overall. The RR showed men and older age groups (≥35 years) exhibiting higher mortality risks. The temporal trend of RR allowed us to identify spatial mortality hotspots mainly in chapters related to circulatory, endocrine, and respiratory diseases, forming four geographical clusters in Mexico City that show persistent high risk of mortality. Conclusions: The spatiotemporal analysis highlights municipalities and vulnerable populations with a consistently elevated mortality risk. These findings emphasize the need for monitoring NCD mortality patterns at both the municipal and metropolitan levels to address disparities and guide the implementation of health policies aimed at reducing mortality risk in vulnerable populations. Full article