Incidence idiopatických střevních zánětů (IBD) se stále zvyšuje. IBD jsou pro pacienta vysokou zátěží a stávají se významným socioekonomickým problémem. Správná a včasná diagnostika je rozhodující pro adekvátní léčbu, která by v nejlepším případě měla zabránit nebo alespoň minimalizovat riziko strukturálních změn v trávicí trubici, a tím zlepšit výhled nemocných s IBD.
The incidence of idiopathic bowel disease (IBD) is increasing. IBDs are a high patient burden and are becoming a significant socioeconomic problem. Correct and early diagnosis is crucial for adequate treatment, which in the best case should prevent or at least minimize the risk of structural changes in the digestive tract, thus improving the outlook of patients with IBD.
Pacienti se syndromem suchého oka tvoří významnou část každodenní oftalmologické péče. Mezi rizikové faktory rozvoje syndromu suchého oka patří i diabetes mellitus. Významnou roli zde hrají změny homeostázy slzného filmu, chronický zánět povrchu oka a doprovázející patologie povrchových nervových vláken rohovky. Cílem této práce bylo popsat stav moderních biomarkerů poškození povrchu oka u pacientů s diabetem 1. typu a posoudit jejich využitelnost pro časný záchyt rozvoje syndromu suchého oka. Materiál a metodika: Do studie bylo zahrnuto celkem 19 pacientů s diabetem 1. typu a 15 pacientů v kontrolní skupině. Pacienti podstoupili detailní vyšetření povrchu oka, odběr biomateriálu k laboratorní analýze hladin matrixové metaloproteinázy 9 (MMP-9), exprese HLA-DR epiteliemi a snímání rohovky pomocí rohovkového konfokálního mikroskopu. Výsledky: Ve skupině pacientů s diabetem 1. typu byla statisticky významně nižší celková délka nervových vláken (p = 0,0482). Osmolarita, citlivost rohovky, vitální barvení povrchu oka, tear break-up time (TBUT) ani MMP-9 v slzném filmu se mezi skupinami statisticky významně nelišily (p = 0,8272, p = 0,6029, p = 0,3507, p = 0,7561 a p = 0,0826 respektive). HLA-DR exprese byla testována na skupině 10 pacientů s diabetem 1. typu a 8 pacientech kontrolní skupiny a u obou skupin byla mírná nebo žádná (p > 0,9999). Závěr: V souladu s dříve publikovanou literaturou jsme v naší studii potvrdili snížení celkové délky nervových vláken subbazálního plexu rohovky u pacientů s diabetem 1. typu oproti subjektům v kontrolní skupině. Neprokázali jsme však změny povrchu oka pomocí standardních ani nových markerů (hladina MMP-9, exprese HLA-DR antigenu na povrchu oka) u pacientů s DM1 oproti kontrolní skupině.
Patients with dry eye syndrome form a significant proportion of those treated in everyday ophthalmology practice. Diabetes mellitus is a major risk factor for the development of dry eye syndrome. Changes in tear film homeostasis, chronic inflammation and subsequent corneal nerve fiber pathology play a key role in its progression. The aim of this study was to describe the status of modern biomarkers of ocular surface damage in patients with type 1 diabetes and asses their utility in early diagnosis of dry eye syndrome. Material and methods: In total the pilot study included 19 patients with type 1 diabetes (T1D) and 15 patients in the control group. All patients underwent a detailed ocular surface examination, sample collection for matrix metalloproteinase-9 (MMP-9) laboratory analysis and epithelial HLA-DR expression evaluation, and in-vivo corneal confocal microscopy. Results: T1D patients showed statistically significantly reduced corneal nerve fiber length (p = 0.0482). The differences between the groups in terms of osmolarity, corneal sensitivity, Oxford score, tear break-up time and MMP-9 level were not statistically significant (p = 0.8272, p = 0.6029, p = 0.3507, p = 0.7561 and p = 0.0826 respectively). HLA-DR expression was examined in 10 T1D patients and 8 patients in the control group. Both groups showed minimal or no expression (p > 0.9999). Conclusion: The previously published literature supports our finding of corneal nerve fiber length reduction in T1D patients compared to controls. However, we did not find any significant changes in standard or modern ocular surface markers (MMP-9 levels, HLA-DR expression) measured in patients with dry eye syndrome.
At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 μm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 μm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 μm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 μm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.
- MeSH
- Biopsy MeSH
- Early Detection of Cancer * methods standards MeSH
- Gastroscopy * standards MeSH
- Risk Assessment MeSH
- Helicobacter Infections complications MeSH
- Humans MeSH
- Stomach Neoplasms * pathology diagnosis therapy MeSH
- Precancerous Conditions * pathology diagnosis therapy MeSH
- Societies, Medical MeSH
- Gastric Mucosa pathology diagnostic imaging MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Practice Guideline MeSH
- Geographicals
- Europe MeSH
Objectives: This study evaluates the test-retest reliability and inter-rater reliability of the MyotonPRO for measuring Achilles tendon stiffness at two standardized sites over various time frames and settings. Methods: Eight healthy participants underwent assessments by three raters over six visits. Tendon stiffness was measured at proximal (mid-portion) and distal (insertional) regions of the Achilles tendon at various time frames (10-15 s, 10-15 min, 24 h, and 14 days apart). Measurements included participant repositioning and two activity stimuli (daily living and sport). Reliability was calculated using the intraclass correlation coefficient (ICC), its 95% confidence interval, coefficient of variation, standard error of measurement, and minimal detectable change. Results: Short-term reliability (10-15 min) was excellent, with an ICC of 0.956 (0.929-0.974). Between days reliability (24 h) was good, with an ICC of 0.889 (0.802-0.938). Between weeks reliability (2 weeks) was good with an ICC of 0.886 (0.811-0.931). Short-term reliability with the simulation of activity of daily living was good, with an ICC of 0.917 (0.875-0.945). Short-term reliability with the simulation of sport was good with an ICC of 0.933 (0.891-0.96). Between days reliability with the simulation of sport was good, with an ICC of 0.920 (0.859-0.955). Conclusions: When used in a standardized position, the MyotonPRO demonstrates reliable repeated measurements of Achilles tendon stiffness. This protocol provides a foundation for clinical research and rehabilitation by clarifying expected reliability across minutes, days, and weeks, thus aiding clinicians and researchers in monitoring tendon adaptations and making evidence-based decisions.
- Publication type
- Journal Article MeSH
INTRODUCTION: Stem cells derived from adipose tissue are gaining popularity in the field of regenerative medicine due to their adaptability and clinical potential. Their rapid growth, ability to differentiate, and easy extraction with minimal complications make adipose-derived stem cells (ADSCs) a promising option for many treatments, particularly those targeting bone-related diseases. This study analyzed gene expression in canine ADSCs subjected to long-term culture and osteogenic differentiation. METHODS: ADSCs were isolated from discarded surgical waste and cultured for 14 days with and without differentiation media to assess osteogenic changes. RNA sequencing (RNA-seq) and bioinformatical analysis were performed to obtain comprehensive transcriptomic data. A total of 17793 genes were detected and GO enrichment analysis was performed on the differentially expressed genes to identify significantly up- and downregulated Biological Process (BP) GO terms across each comparison. RESULTS: The upregulation of apoptosis-regulating genes and genes related to circulatory system development suggest an induction of these processes, while the downregulation of neurogenesis and gliogenesis genes points to reciprocal regulation during osteogenic differentiation of canine ADSCs. DISCUSSION: These findings underscore the potential of ADSCs in bone regeneration and offer valuable insights for advancing tissue engineering, however further studies, including proteomic analyses, are needed to confirm these patterns and their biological significance.
- Publication type
- Journal Article MeSH
INTRODUCTION: The methods for diagnosing compartment syndrome non-invasively remain under debate. Bioimpedance measurements offer a promising avenue in clinical practice, detecting subtle changes in organ impedance due to volume shifts. This study explores bioimpedance measurement as a novel, painless method for diagnosing compartment syndrome, potentially enabling continuous monitoring. OBJECTIVE: This work aims to develop a prototype device for non-invasive diagnosis of compartment syndrome based on bioimpedance changes and assess initial results through in vitro experiments on inanimate biological material. We assume a change in the bioimpedance value after the application of physiological solution. MATERIALS AND METHODS: Between 2018 and 2022, a prototype device for diagnosing limb compartment syndrome was collaboratively developed with the Department of Cybernetics and Biomedical Engineering at the Technical University of Ostrava, Czech Republic. This device operates by comparing bioimpedance between two compartments, one of which is pathologically affected (experiencing compartment syndrome). The Bioimpedance Analyzer for Compartment Syndrome (BACS) has been utilized to conduct measurements on inanimate biological material in laboratory settings. Two samples of duck and chicken tissue, as well as piglets, were employed for these experiments. According to the size of sample was compartment syndrome simulated by injecting 20-120 mL saline into one limb (breast) while leaving the other as a control. Invasive intramuscular pressure measurements were conducted post-saline injection using a conventional device (Stryker). Changes in bioimpedance were evaluated following saline application. RESULTS: The non-invasive bioimpedance measurement instrument has been developed. It meets the safety requirements of European standard EN 60601-1. Measurement of accuracy showed minimal deviation for both channels (1.08% for the left channel and 1.84% for the right channel) when measuring on resistors. Ten measurements were conducted using the BACS prototype - two on chicken legs, two on duck breasts, two on duck legs, and four on piglets. Compartment syndrome simulation was achieved for all 10 measurements (IMP variance 31-45 mmHg). Following saline application, a notable decrease in bioimpedance was observed in the compartment simulating compartment syndrome (decrease by 12-78 Ω). CONCLUSION: Non-invasive methods could revolutionize limb compartment syndrome diagnosis, offering advantages such as non-invasiveness and continuous monitoring of compartment swelling.
- Publication type
- Journal Article MeSH
Multiple myeloma (MM) is the second most prevalent hematological malignancy, characterized by infiltration of the bone marrow by malignant plasma cells. Extramedullary disease (EMD) represents a more aggressive condition involving the migration of a subclone of plasma cells to paraskeletal or extraskeletal sites. Liquid biopsies could improve and speed diagnosis, as they can better capture the disease heterogeneity while lowering patients' discomfort due to minimal invasiveness. Recent studies have confirmed alterations in the proteome across various malignancies, suggesting specific changes in protein classes. In this study, we show that MALDI-TOF mass spectrometry fingerprinting of peripheral blood can differentiate between MM and primary EMD patients. We constructed a predictive model using a supervised learning method, partial least squares-discriminant analysis (PLS-DA) and evaluated its generalization performance on a test dataset. The outcome of this analysis is a method that predicts specifically primary EMD with high sensitivity (86.4%), accuracy (78.4%), and specificity (72.4%). Given the simplicity of this approach and its minimally invasive character, this method provides rapid identification of primary EMD and could prove helpful in clinical practice.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma * blood diagnosis MeSH
- Biomarkers, Tumor blood MeSH
- Aged MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods MeSH
- Liquid Biopsy methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Gadolinium-based contrast agents (GBCA) were introduced with high expectations for favorable efficacy, low nephrotoxicity, and minimal allergic-like reactions. Nephrogenic systemic fibrosis and proven gadolinium retention in the body including the brain has led to the restriction of linear GBCAs and a more prudent approach regarding GBCA indication and dosing. In this review, we present the chemical, physical, and clinical aspects of this topic and aim to provide an equanimous and comprehensive summary of contemporary knowledge with a perspective of the future. In the first part of the review, we present various elements and compounds that may serve as MRI contrast agents. Several GBCAs are further discussed with consideration of their relaxivity, chelate structure, and stability. Gadolinium retention in the brain is explored including correlation with the presence of metalloprotein ferritin in the same regions where visible hyperintensity on unenhanced T1-weighted imaging occurs. Proven interaction between ferritin and gadolinium released from GBCAs is introduced and discussed, as well as the interaction of other elements with ferritin; and manganese in patients with impaired liver function or calcium in Fahr disease. We further present the concept that only high-molecular-weight forms of gadolinium can likely visibly change signal intensity on unenhanced T1-weighted imaging. Clinical data are also presented with respect to potential neurological manifestations originating from the deep-brain nuclei. Finally, new contrast agents with relatively high relaxivity and stability are introduced. CRITICAL RELEVANCE STATEMENT: GBCA may accumulate in the brain, especially in ferritin-rich areas; however, no adverse neurological manifestations have been detected in relation to gadolinium retention. KEY POINTS: Gadolinium currently serves as the basis for MRI contrast agents used clinically. No adverse neurological manifestations have been detected in relation to gadolinium retention. Future contrast agents must advance chelate stability and relativity, facilitating lower doses.
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND AND PURPOSE: The ANNEXA-4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. METHODS: Thirty patients were randomly selected from the ANNEXA-4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty-eight different ANNEXA-4 subjects were also randomly selected to assess intra-rater reliability of total ICrH volume measurement change at baseline and 12-h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA-4. RESULTS: Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. CONCLUSION: Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.
- MeSH
- Adult MeSH
- Factor Xa * MeSH
- Factor Xa Inhibitors administration & dosage therapeutic use MeSH
- Intracranial Hemorrhages * MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain diagnostic imaging MeSH
- Recombinant Proteins administration & dosage MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. Trypanosoma brucei can exploit this by internalising haptoglobin-haemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-/-) on T. brucei brucei infection and the parasite ́s capacity to internalise haemoglobin in a Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma between Hp-/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by T. b. brucei during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice, it suggests that T. b. brucei employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways.
- MeSH
- Haptoglobins * genetics metabolism MeSH
- Hemoglobins * metabolism MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Proteomics methods MeSH
- Trypanosoma brucei brucei * metabolism MeSH
- Trypanosomiasis, African * parasitology immunology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH