Background and Objectives: Aortic stenosis (AS) is a frequent valvular disease characterized by the obstruction of left ventricular outflow. The resulting hemodynamic and structural changes create an arrhythmogenic substrate, with sudden cardiac death (SCD) often caused by ventricular arrhythmias (VAs) being a feared complication. This review examines the relationship between severe AS and VA, detailing the epidemiology, pathophysiological mechanisms, risk factors, and management approaches prior to aortic valve replacement (AVR). Materials and Methods: We conducted a comprehensive narrative review of the historical and contemporary literature investigating ventricular arrhythmias in severe aortic stenosis. Literature searches were performed in PubMed, MEDLINE, and Scopus databases using keywords, including "aortic stenosis", "ventricular arrhythmia", "sudden cardiac death", and "aortic valve replacement". Both landmark historical studies and modern investigations utilizing advanced monitoring techniques were included to provide a complete evolution of the understanding. Results: The prevalence of ventricular ectopy and non-sustained ventricular tachycardia increases with AS severity and symptom onset. Left ventricular hypertrophy, myocardial fibrosis, altered electrophysiological properties, and ischemia create the arrhythmogenic substrate. Risk factors include the male sex, concomitant aortic regurgitation, elevated filling pressures, and syncope. Diagnostic approaches range from standard electrocardiography to continuous monitoring and advanced imaging. Management centers on timely valve intervention, with medical therapy serving primarily as a bridge to AVR. Conclusions: Ventricular arrhythmias represent a consequence of valvular pathology in severe AS rather than an independent entity. Their presence signals advanced disease and a heightened risk for adverse outcomes. Multidisciplinary management with vigilant monitoring and prompt surgical referral is essential. Understanding this relationship enables clinicians to better identify high-risk patients requiring urgent intervention before life-threatening arrhythmic events occur.

• MeSH
• Aortic Valve Stenosis * complications   surgery   physiopathology   MeSH
• Heart Valve Prosthesis Implantation * methods   MeSH
• Tachycardia, Ventricular etiology   MeSH
• Humans MeSH
• Death, Sudden, Cardiac etiology   MeSH
• Risk Factors MeSH
• Arrhythmias, Cardiac * etiology   physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Leukemia is driven by complex interactions within the inherently hypoxic bone marrow microenvironment, impacting both disease progression and therapeutic resistance. Co-cultivation of leukemic cells with feeder cells has emerged as a valuable tool to mimic the bone marrow niche. This study explores the interplay between human commercial SD-1 and patient-derived UPF26K leukemic cell lines with feeders - human fibroblasts (NHDF) and mesenchymal stem cells (hMSCs) under normoxic and hypoxic conditions. RESULTS: Co-cultivation with feeders significantly enhances proliferation and glycolytic activity in the SD-1 cells, improving their viability, while this interaction inhibits the growth and glucose metabolism of the feeders, particularly NHDF. In contrast, UPF26K cells show reduced proliferation when co-cultivated with the feeders while this interaction stimulates NHDF and hMSCs proliferation and glycolysis but reduce their mitochondrial metabolism with hypoxia amplifying these effects. CONCLUSIONS: Cells that switch to glycolysis during co-cultivation, particularly under hypoxia, benefit most from these low oxygen conditions. Due to this leukemic cells' response heterogeneity, targeting microenvironmental interactions and oxygen levels is crucial for personalized leukemia therapy. Advancing co-cultivation models, particularly through innovations like spheroids, can further enhance in vitro studies of primary leukemic cells and support the testing of novel therapies.

• MeSH
• Fibroblasts * metabolism   MeSH
• Glycolysis MeSH
• Cell Hypoxia MeSH
• Coculture Techniques methods   MeSH
• Leukemia * pathology   metabolism   MeSH
• Humans MeSH
• Mesenchymal Stem Cells * metabolism   MeSH
• Mitochondria metabolism   MeSH
• Cell Line, Tumor MeSH
• Tumor Microenvironment MeSH
• Cell Proliferation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Previous studies have indicated that progression independent of relapse activity (PIRA) is uncommon in patients with aquaporin- 4 antibody-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD). However, the patterns of disability accumulation in seronegative NMOSD are unknown. This study aimed to evaluate the prevalence of PIRA and relapse-associated worsening (RAW) in seronegative NMOSD. METHODS: We conducted a retrospective, multicentre cohort study of seronegative NMOSD patients from the MSBase registry. Inclusion criteria required at least three recorded expanded disability status scale (EDSS) scores: baseline, progression, and 6 months confirmed disability progression (CDP). For those with 6-month CDP, the presence or absence of relapse between baseline and progression determined the classification as RAW or PIRA, respectively. Descriptive statistics were employed to present the data. RESULTS: This study included 93 patients, with a median follow-up duration of 5.0 years (Q1 2.8, Q3 8.4). The cohort predominantly consisted of female patients (77.4%), with a median age of onset of 33.9 years (Q1 26.1, Q3 41.2). PIRA was observed in 1 case (1.1%), whilst RAW was documented in 7 cases (7.5%). CONCLUSION: This international cohort study confirms that CDP is uncommon in seronegative NMOSD. Given more than three quarters of CDP occur due to RAW, therapeutic strategies should focus primarily on preventing relapses.

• MeSH
• Aquaporin 4 immunology   MeSH
• Autoantibodies blood   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Neuromyelitis Optica * physiopathology   epidemiology   blood   immunology   MeSH
• Disability Evaluation MeSH
• Disease Progression * MeSH
• Recurrence MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Vysokoškolská učebnice, která se zaměřuje na ošetřovatelství ve vnitřním lékařství.; Moderní učebnice od renomovaného autorského kolektivu ke zvládnutí studijních povinností v předmětu Ošetřovatelství v klinických oborech, zaměřená na péči o nemocné na interních odděleních. Učebnice je doporučena pro studenty vyššího typu studia (např. VOŠZ, bakalářské a magisterské studium ošetřovatelství, specializační studium). Výklad v rámci systémových onemocnění je členěn na část odbornou a podle nejnovějších požadavků na část ošetřovatelskou s kazuistikou + ošetřovatelské diagnózy v NANDA doménách v ošetřovatelském procesu. Ošetřovatelský proces je v jednotlivých velkých kapitolách popsán postupně u 1) onemocnění srdce a oběhového systému, 2) onemocnění dýchacího systému, 3) onemocnění nervového systému, 4) onemocnění pohybového systému, 5) onemocnění infekčních a 6) geriatrických pacientů.

• MeSH
• Nursing MeSH
• Internal Medicine MeSH

• Conspectus
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• ošetřovatelství
• vnitřní lékařství
• NML Publication type
• kolektivní monografie
• učebnice vysokých škol

INTRODUCTION: Acute ischemic stroke (AIS) is the second leading cause of death and one of the leading causes of long-term disability globally. Endovascular thrombectomy (EVT) has revolutionized treatment for large vessel occlusion (LVO), providing 20% increase in post-stroke functional independence compared to intravenous thrombolysis (IVT) alone. Despite its proven efficacy, EVT is underutilized. While it is suitable for at least 15-20% of AIS patients, its mean adoption ranges from less than 1% to 7% in different areas. AREAS COVERED: This review highlights key findings from pivotal randomized controlled trials and real-world data, focusing on patient selection criteria, advancements in thrombectomy devices, and procedural innovations. A comprehensive literature search was performed using PubMed, Scopus, EMBASE and the Cochrane Library for relevant randomized controlled trials and observational studies. EXPERT OPINION: Disparity in access to EVT requires strategic investments in healthcare systems and international multidisciplinary collaboration. Enhancing geographic coverage with thrombectomy-capable centers and optimizing prehospital triage systems are essential. Bridging the gap between treatment capability and real-world implementation is critical to improving global AIS outcomes.

• MeSH
• Endovascular Procedures * methods   MeSH
• Ischemic Stroke * surgery   MeSH
• Humans MeSH
• Randomized Controlled Trials as Topic MeSH
• Thrombectomy * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

It has been demonstrated that freezing-induced acidity changes have an impact on the structural integrity, degree of aggregation, and chemical stability of frozen food and pharmaceutical products. The stability of the compounds in solutions is maintained by the presence of buffers. However, many buffers are unsuitable for applications involving freezing as this process substantially alters the acidity. In this study, we determine the effect of initial pH, concentration, and cooling rate on the freezing-induced change in acidity of phosphate buffered saline (PBS) in the frozen state via UV-VIS spectroscopy. Furthermore, we examine the impact of individual salts present in PBS and discuss the mechanisms affecting the resulting acidity that we approximate via Hammett acidity function (H2-).

• MeSH
• Phosphates * chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Buffers MeSH
• Saline Solution * chemistry   MeSH
• Freezing MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function? METHODS: We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings. RESULTS: The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells. CONCLUSIONS: Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.

• MeSH
• alpha-Defensins metabolism   MeSH
• Cell Differentiation MeSH
• Humans MeSH
• Mice MeSH
• Colonic Neoplasms * pathology   genetics   microbiology   metabolism   MeSH
• Organoids metabolism   MeSH
• Paneth Cells metabolism   MeSH
• Goblet Cells metabolism   MeSH
• Wnt Signaling Pathway MeSH
• Gastrointestinal Microbiome * MeSH
• Intestine, Small * metabolism   pathology   microbiology   MeSH
• Transcription Factor 4 * metabolism   genetics   MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Epilepsy, affecting over 50 million people globally, presents a significant neurological challenge. Effective prevention of epileptic seizures relies on proper administration and monitoring of Anti-Seizure Medication (ASMs). Therapeutic Drug Monitoring (TDM) ensures optimal dosage adjustment, minimizing adverse effects and potential drug interactions. While traditional venous blood collection for TDM may be stressful, emerging alternative sampling methods, particularly Dried Blood Spot (DBS) or oral fluid offer less invasive way of sampling. This study aimed to develop and validate an analytical method for the determination of lamotrigine in such alternative samples. The sample, either DBS or oral fluid, was subjected to extraction, evaporation, and reconstitution in 15 % acetonitrile containing 0.1 % formic acid. A Kinetex C18 Polar column was used for liquid chromatographic separation and MS in ESI+ mode was used for detection and quantitation of lamotrigine using an isotopically labelled internal standard according to EMA guidelines. The calibration range of the developed method enables the determination of lamotrigine in the concentration range of 1-30 μg/mL in DBS and 0.5-20 μg/mL in oral fluid. Oral fluid and DBS samples from patients treated with lamotrigine analysed by the developed method were compared to plasma concentrations measured by the hospital's accredited laboratory. Preliminary results indicate a promising potential for these alternative matrices in clinical TDM applications. By offering a less invasive sampling approach, this method improves the accessibility and safety of pharmacotherapy for epilepsy patients. The results of this study lay the foundation for further clinical applications by implementing alternative matrix TDM, which may significantly advance personalized care in epilepsy management.

• MeSH
• Anticonvulsants * analysis   blood   MeSH
• Chromatography, Liquid methods   MeSH
• Epilepsy drug therapy   MeSH
• Calibration MeSH
• Liquid Chromatography-Mass Spectrometry MeSH
• Lamotrigine * analysis   blood   MeSH
• Humans MeSH
• Limit of Detection MeSH
• Drug Monitoring * methods   MeSH
• Reproducibility of Results MeSH
• Saliva * chemistry   MeSH
• Tandem Mass Spectrometry methods   MeSH
• Dried Blood Spot Testing * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

PURPOSE: Revision total hip arthroplasty (rTHA) is an increasingly common procedure due to the growing number of primary total hip arthroplasties (THAs) performed worldwide. This study evaluates the long-term implant survival, functional outcomes, and radiographic performance of cemented femoral stem (Beznoska s.r.o., Kladno, Czechia) in rTHA. METHODS: A retrospective analysis was conducted on 183 patients who underwent rTHA with cemented stem between March 2012 and December 2023. The mean follow-up duration was 71.26(± 39.31) months. Implant survival was analyzed using Kaplan-Meier survival estimates, and failure modes were assessed. Radiographic changes were classified using the Gruen Zones system. Functional outcomes were evaluated using the Harris Hip Score (HHS). Cox proportional hazard models were applied to identify prognostic factors influencing implant survival. RESULTS: The five-year implant survival rate was 98.1%, declining to 83.9% at twelve years. The overall failure rate was 3.83%, with periprosthetic infection (4 cases) being the most common cause, followed by aseptic loosening (2 cases). Radiographic changes were observed in 24.03% of cases, predominantly in Gruen Zones 2, 6, and 1. Functional outcomes were favorable, with a mean HHS of 81.28(± 5.74), comparable to outcomes reported for uncemented revision stems. Age, stem diameter, and stem length did not significantly impact implant survival. CONCLUSION: The cemented stem demonstrated favourable long-term survival, with high implant retention rates. Functional outcomes indicated overall satisfactory performance. Radiographic evaluation revealed localized changes around the implant, predominantly in Gruen Zones 2, 6, and 1. Implant failure was relatively rare, with periprosthetic infection being the most common cause.

• MeSH
• Cementation MeSH
• Adult MeSH
• Kaplan-Meier Estimate MeSH
• Bone Cements MeSH
• Hip Joint diagnostic imaging   surgery   MeSH
• Hip Prosthesis * adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Arthroplasty, Replacement, Hip * methods   instrumentation   adverse effects   MeSH
• Prosthesis Design MeSH
• Radiography MeSH
• Reoperation * MeSH
• Retrospective Studies MeSH
• Prosthesis Failure * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Data registries lack a definitive classification system that distinguishes different locations of colon cancer from one another. OBJECTIVE: To establish an international consensus on the definition of primary colon cancer segment locations. DESIGN: Between December 2022 and June 2023, the Delphi survey study was conducted to seek opinions from relevant international experts and eventually develop a consensus definition of each colon cancer segment. SETTING: Three-round online-based Delphi survey study. INTERVENTIONS: The online survey included 17 questions. In the first 2 rounds, participating experts were asked to rank each statement on a scale of 1 (least relevant) to 9 (most relevant). Consensus statements and definitions were revised according to the results for statements obtaining a consensus score of 7 to 9. During the third round and online meeting, definitions and statements that reached a moderate or high consensus (above 4 for more than 70% of participants) were included. MAIN OUTCOME MEASURES: The primary goal of our project was focused on precisely localizing the specific segment affected by primary colon cancer rather than identifying surgical treatment or type of resection needed for a particular segment. RESULTS: The first round included 331 experts; 301 (91%) completed the second round and 295 (98%) completed the final round. Experts strongly supported the use of a "10-cm rule" to describe colon cancer sites at the flexures and anatomical landmarks for other segments. Regarding the definition of rectosigmoid cancer, experts from United States and Europe reached a high consensus that the term rectosigmoid as a colon cancer location must be abolished in contrast to experts from Asia. The description of overlapping segments of cancers achieved a consensus of 64%. LIMITATIONS: Subjective decisions are based on individual expert clinical experience. CONCLUSIONS: This Delphi survey, the first internationally conducted consensus study, achieved a remarkable level of consensus among a panel of global experts. Ambiguity still exists regarding overlapping lesions. See Video Abstract . ESTANDARIZACIN DE LA DEFINICIN DE CADA SEGMENTO DE CNCER DE COLON CONSENSO DELPHI SOBRE LA TOMA DE DECISIONES CLNICAS PARA RESULTADOS ONCOLGICOS: ANTECEDENTES:Las bases de datos carecen de un sistema de clasificación definitivo que distinga las diferentes localizaciones del cáncer de colon.OBJETIVO:Establecer un consenso internacional sobre la definición de las localizaciones de los segmentos del cáncer de colon priamrio.DISEÑO:Entre diciembre de 2022 y junio de 2023, se realizó un estudio Delphi para recabar la opinión de expertos internacionales relevantes y, finalmente, desarrollar una definición consensuada de cada segmento del cáncer de colon.ESCENARIO:Estudio Delphi en línea de 3 rondas.INTERVENCIONES:La encuesta en línea incluyó 17 preguntas. En las dos primeras rondas, se pidió a los expertos participantes que calificaran cada afirmación en una escala del 1 al 9 (9 es la más relevante). Las afirmaciones y definiciones de consenso se revisaron según los resultados, obteniendo una puntuación de consenso de 7 a 9. Durante la tercera ronda y la reunión en línea, se incluyeron las definiciones y afirmaciones que alcanzaron un consenso moderado o alto (superior a 4 en más del 70 % de los participantes).MEDIDA PRINCIPALES DE RESULTADOS:El objetivo principal de nuestro proyecto se centró en localizar con precisión el segmento específico afectado por el cáncer de colon primario, en lugar de identificar el tratamiento quirúrgico o el tipo de resección necesario para un segmento en particular.RESULTADOS:La primera ronda incluyó a 331 expertos, 301 (91%) completaron la segunda ronda y 295 (98%) completaron la ronda final. Los expertos apoyaron firmemente el uso de una "regla de 10 cm" para describir las localizaciones del cáncer de colon en las flexuras y puntos de referencia anatómicos para otros segmentos. En cuanto a la definición de cáncer rectosigmoideo, expertos de América y Europa alcanzaron un alto consenso en la necesidad de abolir el término "rectosigmoide" como localización del cáncer de colon, a diferencia de los expertos de Asia. La descripción de los cánceres en segmentos que se superponen a alcanzó un consenso del 64%.LIMITACIONES:Las decisiones subjetivas se basan en la experiencia clínica individual de cada experto.CONCLUSIONES:Esta encuesta Delphi, el primer estudio de consenso realizado a nivel internacional, alcanzó un notable nivel de consenso entre un panel de expertos globales. Todavía existe ambigüedad en cuanto a las lesiones superpuestas. (Traducción-Dr. Jorge Silva Velazco ).

• MeSH
• Delphi Technique MeSH
• Clinical Decision-Making * methods   MeSH
• Consensus MeSH
• Humans MeSH
• Colonic Neoplasms * pathology   classification   diagnosis   surgery   MeSH
• Surveys and Questionnaires MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH