Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.
BACKGROUND: Duchenne muscular dystrophy (DMD) patients are monitored periodically for cardiac involvement, including cardiac MRI with gadolinium-based contrast agents (GBCA). Texture analysis (TA) offers an alternative approach to assess late gadolinium enhancement (LGE) without relying on GBCA administration, impacting DMD patients' care. The study aimed to evaluate the prognostic value of selected TA features in the LGE assessment of DMD patients. RESULTS: We developed a pipeline to extract TA features of native T1 parametric mapping and evaluated their prognostic value in assessing LGE in DMD patients. For this evaluation, five independent TA features were selected using Boruta to identify relevant features based on their importance, least absolute shrinkage and selection operator (LASSO) to reduce the number of features, and hierarchical clustering to target multicollinearity and identify independent features. Afterward, logistic regression was used to determine the features with better discrimination ability. The independent feature inverse difference moment normalized (IDMN), which measures the pixel values homogeneity in the myocardium, achieved the highest accuracy in classifying LGE (0.857 (0.572-0.982)) and also was significantly associated with changes in the likelihood of LGE in a subgroup of patients with three yearly examinations (estimate: 23.35 (8.7), p-value = 0.008). Data are presented as mean (SD) or median (IQR) for normally and non-normally distributed continuous variables and numbers (percentages) for categorical ones. Variables were compared with the Welch t-test, Wilcoxon rank-sum, and Chi-square tests. A P-value < 0.05 was considered statistically significant. CONCLUSION: IDMN leverages the information native T1 parametric mapping provides, as it can detect changes in the pixel values of LGE images of DMD patients that may reflect myocardial alterations, serving as a supporting tool to reduce GBCA use in their cardiac MRI examinations.
- MeSH
- Child MeSH
- Muscular Dystrophy, Duchenne * diagnostic imaging pathology MeSH
- Gadolinium MeSH
- Contrast Media MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Adolescent MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: To evaluate the effectiveness and safety of sonolysis using a low intensity 2 MHz pulsed wave ultrasound beam during carotid endarterectomy. DESIGN: Multicentre, phase 3, double blind, randomised controlled trial. SETTING: 16 European centres. PARTICIPANTS: 1004 patients (mean age 68 years; 312 (31%) female) were enrolled in the study between 20 August 2015 and 14 October 2020 until the interim analysis was performed. INTERVENTIONS: Sonolysis (n=507) versus sham procedure (n=497). MAIN OUTCOME MEASURES: The primary endpoint was the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. The incidence of new ischaemic lesions on follow-up brain magnetic resonance imaging was the main substudy endpoint, and incidence of intracranial bleeding was the main safety endpoint. RESULTS: The results favoured the sonolysis group for the primary endpoint (11 (2.2%) v 38 (7.6%); risk difference -5.5%, 95% confidence interval (CI) -8.3% to -2.8%; P<0.001), as well as in the substudy for magnetic resonance imaging detected new ischaemic lesions (20/236 (8.5%) v 39/224 (17.4%); risk difference -8.9%, -15% to -2.8%; P=0.004). Sensitivity analysis resulted in a risk ratio for sonolysis of 0.25 (95% CI 0.11 to 0.56) for ischaemic stroke and 0.23 (0.07 to 0.73) for transient ischaemic attack within 30 days. Sonolysis was found to be safe, and 94.4% of patients in the sonolysis group were free from serious adverse events 30 days after the procedure. CONCLUSION: Sonolysis was safe for patients undergoing carotid endarterectomy and resulted in a significant reduction in the composite incidence of ischaemic stroke, transient ischaemic attack, and death within 30 days. TRIAL REGISTRATION: Clinicaltrials.gov NCT02398734.
- MeSH
- Double-Blind Method MeSH
- Ischemic Stroke prevention & control epidemiology MeSH
- Endarterectomy, Carotid * adverse effects methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Aged MeSH
- Carotid Stenosis surgery MeSH
- Ischemic Attack, Transient * prevention & control etiology MeSH
- Ultrasonic Therapy methods adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Genetika neurodegeneratívnych demencií je turbulentnou témou súčasnosti. Na jednej strane sa postupne zvyšuje množstvo génov zapojených do patogenézy neurodegeneratívnych procesov, na druhej strane vystupuje problém s interpretáciou dosiahnutých výsledkov. Alzheimerova choroba (AD) a demencia s Lewyho telieskami (DLB) predstavujú v súčasnosti dobre definované klinické jednotky. Alzheimerova choroba má jasne určené kauzálne gény (APP, PSEN1, PSEN2) a významný gén susceptibility (APOE). Popri nich sa postupne objavujú nové gény susceptibility, ktoré modifikujú klinický obraz, vek nástupu ochorenia a spolu s APOE vytvárajú komplikované genetické pozadie. Demencia s Lewyho telieskami je heterogénnejšou entitou ako Alzheimerova choroba z klinického aj genetického hľadiska. Génmi susceptibility DLB sú viaceré gény zdieľané s Alzheimerovou chorobou, Parkinsonovou chorobou (PD), frontotemporálnou demenciou (FTD) a inými neurodegeneráciami. V našom príspevku sa snažíme sumarizovať genetické pozadie AD a DLB, charakterizovať ich podobnosti a rozdiely a poukázať na komplexnosť neurodegeneratívneho ekosystému ("neurodegeneratómu").
The genetics of neurodegenerative dementias is a turbulent topic. On the one hand, the number of genes involved in the pathogenesis of neurodegenerative processes is gradually increasing, on the other hand, the problem of interpretation of the results is emerging. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) represent currently well-defined clinical entities. AD has clearly defined causal genes (APP, PSEN1, PSEN2) and a major susceptibility gene (APOE). In addition to these, new susceptibility genes are gradually emerging that modify the clinical picture, the age of onset and, together with APOE, create a complicated genetic background. Dementia with Lewy bodies (DLB) is a more heterogeneous entity than Alzheimer's disease, both clinically and genetically. DLB susceptibility genes are multiple genes shared with Alzheimer`s disease, Parkinson disease, frontotemporal dementia (FTD) and other neurodegenerations. In our paper, we aim to summarize the genetic background of both AD and DLB, to characterize their similarities and differences, and to highlight the complexity of the neurodegenerative ecosystem ("neurodegeneratome").
- MeSH
- Alzheimer Disease * diagnosis genetics MeSH
- Apolipoproteins metabolism MeSH
- Lewy Body Disease * diagnosis genetics MeSH
- Epigenomics classification MeSH
- Genetic Background MeSH
- Genetic Testing methods MeSH
- Humans MeSH
- Neurodegenerative Diseases diagnosis genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Farmakologická léčba epilepsie je čím dál složitější, vyžaduje komplexní znalosti a klinickou zkušenost. Až jedna čtvrtina lidí s epilepsií užívá více než jeden protizáchvatový lék, mají časté komorbidity, ale i akutní či chronická interkurentní onemocnění vyžadující podávání dalších léčiv. Farmakokinetické a farmakodynamické lékové interakce jsou zpravidla dobře popsány a informace o nich snadno dohledatelné. Méně víme o aktivním influxním/efluxním transportu léčiv jak v průběhu jejich vstřebávání z gastrointestinálního traktu, tak při jejich přestupu přes hematoencefalickou bariéru. Neurolog potřebuje při volbě kombinace/kombinací protizáchvatových léků a/nebo léčivých přípravků z jiných indikací vědět, zda mezi nimi může dojít ke klinicky významné interakci, jaký je její mechanismus a projevy, jak vysoká je pravděpodobnost, že k ní dojde a jak bude závažná.
Pharmacological treatment of epilepsy is more and more complex, requiring comprehensive knowledge and clinical experience. Up to one-quarter of people with epilepsy take more than one antiseizure medication, and they have frequent comorbidities, as well as acute or chronic intercurrent diseases requiring the administration of other drugs. Pharmacokinetic and pharmacodynamic drug interactions are usually well described and information about them is easy to find. We know less about drugs' active influx/efflux transport both during their absorption from the gastrointestinal tract and their transfer across the blood-brain barrier. When choosing a combination(s) of antiseizure medication and/or drugs for other indications, the neurologist needs to know whether a clinically significant interaction can occur between them, what its mechanism and manifestations are, how high the probability of its occurrence and how severe it will be.
- MeSH
- Anticonvulsants * pharmacokinetics pharmacology classification therapeutic use MeSH
- Epilepsy diagnosis drug therapy MeSH
- Blood-Brain Barrier drug effects MeSH
- Carbamazepine pharmacokinetics pharmacology therapeutic use MeSH
- Valproic Acid pharmacokinetics pharmacology therapeutic use MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Mezi celosvětově rozšířené sexuálně přenosné nemoci je řazeno infekční onemocnění syfilis. Kvůli neuroinvazivitě infikujícího kmene treponem se u pacientů můžeme setkat s velmi pestrým postižením centrální nervové soustavy, k jehož projevům může dojít během kteréhokoli stadia onemocnění. Článek obsahuje přehled jednotlivých stadií syfilis a neurosyfilis. Formou kazuistického sdělení mladého pacienta popisujeme terciální stadium syfilis pod obrazem progresivní paralýzy.
The infectious disease syphilis is among the most common sexually transmitted diseases worldwide. Due to the neuroinvasiveness of the infecting treponemal strain, patients can encounter a wide variety of central nervous system involvement, which can occur during any stage of the disease. This article reviews the different stages of syphilis and neurosyphilis. In the form of case report of a young patient, we describe the late stage of syphilis as general paresis.
- MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Case Reports as Topic MeSH
- Cognitive Dysfunction diagnosis etiology microbiology MeSH
- Humans MeSH
- Neurologic Manifestations MeSH
- Neurosyphilis * diagnosis epidemiology complications MeSH
- Sexually Transmitted Diseases diagnosis drug therapy classification MeSH
- Treponema pathogenicity MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
Představujeme kazuistiku 34leté pacientky, heterozygotky Leidenské mutace, postižené autozomálně dominantní polycystickou chorobou ledvin (AD PCKD), přijaté pro náhle vzniklé symptomy netraumatické inkompletní transverzální míšní léze v úrovni Th4-5. Vstupní zobrazení mozku a celé míchy magnetickou rezonancí (MR) neprokázalo žádné ložiskové změny. Pomocí CT angiografie jsme vyloučili disekci aorty. V likvoru byl normální nález. Třetího dne se na kontrolní MR hrudní míchy vykreslilo ložisko myelopatie přibližně v úrovni Th5. Pátého dne bylo toto ložisko již bez podstatného vývoje. Dle klinického průběhu a výsledků komplementárních vyšetření jsme stav hodnotili jako míšní ischemii. Doplněná transezofageální echokardiografie a bubble test prokázaly high‐grade permanentní pravo-levý zkrat při otevřeném foramen ovale (FOP). Další laboratorní a zobrazovací vyšetření k objasnění etiologie byla negativní. Byla indikována okluze FOP. Pacientka rehabilitovala a její zdravotní stav se postupně zlepšoval.
We present a case report of a 34-year-old female patient, heterozygote f.V Leiden, affected by autosomal dominant polycystic kidney disease (AD PCKD), admitted for sudden onset of symptoms of a non-traumatic incomplete transverse spinal cord lesion at the Th4-5 level. Initial magnetic resonance (MR) imaging of the brain and whole spinal cord showed no focal changes. CT angiography was used to exclude aortic dissection. The CSF showed normal findings. On the third day, a follow-up MRI of the thoracic spinal cord showed a focus of myelopathy at approximately Th5 level. On the fifth day, this lesion was no longer significantly developed. We assessed the condition as spinal cord ischemia based on the clinical course and the results of complementary examinations. The supplementary transesophageal echocardiography and bubble test revealed a high-grade, permanent right-to-left shunt with a patent foramen ovale (FOP). Further laboratory and imaging investigations to clarify the aetiology of spinal cord infractions were negative. FOP occlusion was indicated. The patient was rehabilitated and her condition gradually improved.
- MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Foramen Ovale, Patent diagnosis complications MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Spinal Cord Ischemia * diagnosis etiology classification rehabilitation MeSH
- Polycystic Kidney, Autosomal Dominant diagnosis MeSH
- Prednisone pharmacology therapeutic use MeSH
- Pregabalin pharmacology therapeutic use MeSH
- Thrombophilia diagnosis genetics complications MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Roztroušená skleróza (RS) je chronické autoimunitní onemocnění s prvky neurodegenerace, které postihuje nejčastěji mladé dospělé ve věku 20-40 let. Onemocnění je 3× častější u žen než u mužů. Mezi nejčastější symptomy RS patří poruchy zraku, senzitivní, motorické a sfinkterové dysfunkce. Mezi příznaky, které mohou být poněkud opomíjené, ale přesto velmi ovlivňují kvalitu života a celkový zdravotní stav, patří i poruchy polykání. V uvedené videokazuistice prezentujeme mladou pacientku, u které byla dysfagie jedním z prvních symptomů RS. V rámci kazuistiky popisujeme diagnostiku dysfagie a i následný komplexní terapeutický přístup, který zahrnoval jednak terapii RS, ale i cílenou pravidelnou logopedickou péči.
Multiple sclerosis is a chronic autoimmune disease affecting the central nervous system (CNS) and is characterized by inflammation, demyelination, gliosis, and neuronal loss. This condition manifests with a wide range of neurological symptoms, such as vision impairment, numbness and tingling, focal weakness, bladder and bowel dysfunction, and cognitive impairment. Swallowing disorders are among the symptoms that may be somewhat neglected but nevertheless greatly affect quality of life and overall health. Multiple sclerosis most often affects young adults aged 20-40 years. The disease is 2 to 3 times more common in women than in men. In this video case report, we present a young patient in whom dysphagia was one of the first symptoms of MS. In the case report, we describe the diagnosis of dysphagia and the subsequent complex therapeutic approach, which included both therapy for MS and targeted regular speech therapy.
- Keywords
- ofatumumab,
- MeSH
- Antigens, CD20 pharmacology MeSH
- Diagnosis, Differential MeSH
- Antibodies, Monoclonal, Humanized pharmacology classification therapeutic use MeSH
- Speech-Language Pathology methods MeSH
- Humans MeSH
- Young Adult MeSH
- Deglutition Disorders * diagnosis etiology drug therapy rehabilitation MeSH
- Multiple Sclerosis * diagnosis drug therapy complications MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
PURPOSE: This study aimed to compare general ophthalmologists, retina specialists, and Aireen AI screening system with the clinical reference standard of a three-member high-level expert committee for diabetic retinopathy (DR) in the evaluation of fundus images for DR. PATIENTS AND METHODS: The study was designed as a diagnostic, multicenter, cross-sectional, non-randomized diagnostic study. The cohort included in the clinical investigation consisted of 1274 patients with diabetes mellitus (DM) type I or II. Each patient underwent one-field fundus photography using a non-mydriatic camera to assess findings of DR. One hundred and nineteen subjects (9.3%) were excluded from the clinical investigation based on Aireen system assessment. In the clinical investigation, all images were assessed at three independent levels of evaluation: 1) general ophthalmologists (GO) - without subspecialty training in the retina; 2) retina specialists (RS); and 3) system Aireen. In cases where there may be disagreements amongst groups, the image is referred for assessment by the Diabetic Retinopathy Board (DRB). RESULTS: The overall prevalence of any DR was 31.9% (368 cases out of 1154 DM), according to the DRB. Overall concordance between AI system Aireen and GO and RS assessments in the detection of DR from fundus photography occurred in 734 cases (63.6%). The number of disagreements between Aireen system, GO and RS evaluation occurred in 420 (36.4%) cases. Sensitivity for GO was 87.0% (95% CI: 83.6; 90.4), for RS was 82.9% (95% CI: 79.1; 86.7), and for AI system Aireen was 92.1% (95% CI: 89.3; 94.9). Specificity was 76.5% (95% CI: 73.5; 79.5), 81.2% (95% CI: 78.5; 83.9), and 90.7% (95% CI: 88.7; 92.7) for GO, RS and AI system Aireen, respectively. CONCLUSION: This real-world study illustrates the potential use of AI system Aireen in screening for DR. It exhibits higher sensitivity and specificity compared to telemedicine evaluation of one field fundus image.
- Publication type
- Journal Article MeSH
