Úvod a ciele: Zistilo sa, že obehové časy pečene merané pomocou kontrastnej ultrasonografie a elasticita pečene dokázali predpovedať klinicky signifikantnú portálnu hypertenziu. Nie je však zatiaľ dostatočne preskúmané, či by obehové časy pečene dokázali predpovedať nepriaznivý priebeh aj u pacientov s klinicky diagnostikovanou cirhózou, ktorí vo väčšine prípadov majú klinicky signifikantnú portálnu hypertenziu. Cieľom našej štúdie bolo zhodnotiť význam obehových časov a elasticity pečene v predikcii nepriaznivého priebehu cirhózy a porovnať ich s MELD (model for end-stage liver disease). Metódy: Sledovaná skupina zahŕňala 48 po sebe idúcich ambulantných pacientov s cirhózou v 2.–4. štádiu podľa D´Amica. Pacienti v štádiu 4. mohli mať len ikterus, pacienti s ostatnými komplikáciami portálnej hypertenzie neboli zahrnutí. Meranie obehových časov bolo vykonané počas kontrolného ultrasonografie. Obehové časy boli merané od intravenóznej aplikácie kontrastnej látky (SonoVue) a jej príchodu do hepatálnej žily (venózny čas/hepatic vein arrival time – HVAT) alebo časového rozdielu medzi kontrastným signálom vo vetve a. hepatica a hepatálnej žily (obeh pečene/hepatic transit time – HTT) v sekundách. Elasticita pečene bola meraná pomocou tranzientnej elastografie (Fibroscan). Obehové časy a elasticita boli merané pri vstupe do sledovania. Pacienti boli následne sledovaní počas 1 roka. Nepriaznivý priebeh cirhózy bol definovaný ako objavenie sa klinicky zjavného ascitu alebo hospitalizácie pre chorobu pečene alebo úmrtia. Výsledky: Priemerný vek bol 61 rokov, pomer ženy/muži bol 23/25. Pri vstupe do štúdie bol medián Childova-Pughova skóre 5 (IQR 5,0–6,0), MELD 9,5 (IQR 7,6–12,1), medián HVAT bol 22 s (IQR 19–25) a HTT 6 (IQR 5–9). HTT aj HVAT negatívne korelovali s Childovom-Pughovom skóre (-0,351, resp. -0,441; p = 0,002) a MELD (-0,479, resp. -0,388; p = 0,006) skóre. Po dobu jedného roka bol nepriaznivý priebeh zaznamenaný v 11 prípadoch (22,9 %), vrátane 6 úmrtí a 5 hospitalizácií. Medián HVAT bol v prípadoch s nepriaznivým priebehom 20 s (IQR 19,3–23,5) porovnaní s 22 s (IQR 19 do 26, p = 0,32). Prípady s nepriaznivým priebehom mali signifikantne vyššie MELD (12,9 vs 8,5), Childovo-Pughovo skóre (7,0 vs 5,0) a elasticitu pečene (52,5 vs 21,05 kPa) (p <0,05). AUROC pre HVAT, elasticitu pečene a MELD v predikcii nepriaznivého priebehu bol 0,60 (95% CI 0,414–0,785), 0,767 (0,56–0,98) a 0,813 (0,66–0,97). Čas HVAT nebol schopný predpovedať nepriaznivý klinický výsledok, ale elasticita pečene > 35,3 kPa zvýšila toto riziko 10,3-násobne a MELD > 11 bodov 8,5-násobne. Záver: U pacientov s klinicky diagnostikovanou cirhózou s prítomnou klinicky signifikantnou portálnou hypertenziou obehové časy pečene nepreukázali schopnosť predpovedať nepriaznivý priebeh do jedného roka. Naopak, meranie elasticity pečene sa ukázalo ako klinicky prospešné s prognostickou hodnotou porovnateľnou s MELD. Kľúčové slová: elasticita pečene – klinicky diagnostikovaná cirhóza – MELD – obehové časy pečene – portálna hypertenzia
Introduction and objectives: Hepatic transit times measured by the contrast enhanced ultrasonography and liver elasticity were found to predict a clinically significant portal hypertension. However, these modalities we not yet sufficiently evaluated in predicting adverse clinical outcome in patients with clinically diagnosed cirrhosis (D´Amico stages > 1), having a clinically significant portal hypertension. The aim of our study was to assess the predictive power of the liver transit times and the liver elasticity on an adverse clinical outcome of clinically diagnosed cirrhosis compared with the MELD score. Methods: The study group included 48 consecutive outpatients with cirrhosis in the 2., 3. and 4. D’Amico stages. Patients with stage 4 could have jaundice, patients with other complications of portal hypertension were excluded. Transit times were measured from the time of intravenous administration of contrast agent (Sonovue) to a signal appearance in a hepatic vein (hepatic vein arrival time, HVAT) or time difference between the contrast signal in the hepatic artery and hepatic vein (hepatic transit time, HTT) in seconds. Elasticity was measured using the transient elastography (Fibroscan). The transit times and elasticity were measured at baseline and patients were followed for up for 1 year. Adverse outcome of cirrhosis was defined as the appearance of clinically apparent ascites and/or hospitalization for liver disease and/or death within 1 year. Results: The mean age was 61 years, with female/male ratio 23/25. At baseline, the median Child-Pugh score was 5 (IQR 5.0–6.0), MELD 9.5 (IQR 7.6 to 12.1), median HVAT was 22 s (IQR 19–25) and HTT 6 (IQR 5–9). HTT and HVAT negatively correlated with Child-Pugh (-0.351 and -0.441, p = 0.002) and MELD (-0.479 and -0.388, p = 0.006) scores. The adverse outcome at 1-year was observed in 11 cases (22.9 %), including 6 deaths and 5 hospitalizations. Median HVAT in those with/without the adverse outcome was 20 seconds (IQR 19.3–23.5) compared with 22 s (IQR 19–26, p = 0.32). Cases with adverse outcome had significantly higher MELD (12.9 vs 8.5), Child-Pugh score (7.0 vs 5.0) and the liver elasticity (52.5 vs 21.5 kPa) (p < 0.05). The AUROC of the HVAT, liver elasticity and MELD for the prediction of the adverse outcome was 0.60 (95% CI 0.414 to 0.785), 0.767 (0.56 to 0.98) and 0.813 (0.66 to 0.97). Unlike HVAT, the liver elasticity > 35.3 kPa increased the risk of the adverse outcome 10.3-times and MELD score > 11 points 8.5-times. Conclusion: In patients with clinically diagnosed cirrhosis having a clinically significant portal hypertension hepatic transit times do not predict the 1-year adverse clinical outcome. However, the liver elasticity > 35.3 kPa appears clinically useful with a prognostic value comparable with MELD. Key words: clinically diagnosed cirrhosis – hepatic transit times – liver elasticity – MELD – portal hypertension
- MeSH
- Elasticity Imaging Techniques * methods MeSH
- Risk Assessment MeSH
- Data Interpretation, Statistical MeSH
- Liver Cirrhosis * physiopathology MeSH
- Liver Circulation MeSH
- Contrast Media MeSH
- Middle Aged MeSH
- Humans MeSH
- Hypertension, Portal * physiopathology MeSH
- Predictive Value of Tests MeSH
- Prognosis MeSH
- Blood Flow Velocity MeSH
- Aged MeSH
- Severity of Illness Index MeSH
- Ultrasonography methods MeSH
- Hepatic Veins physiopathology ultrasonography MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Castration MeSH
- Collagen MeSH
- Rats MeSH
- Tensile Strength MeSH
- Elasticity MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
BACKGROUND: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. METHODS: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 μg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. RESULTS: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. CONCLUSION: The formation of scars with the best elasticity was exhibited by addition 1.0 μg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research.
- MeSH
- Chitosan * MeSH
- Fibroblast Growth Factor 2 * MeSH
- Wound Healing drug effects MeSH
- Cicatrix, Hypertrophic MeSH
- Collagen MeSH
- Skin MeSH
- Disease Models, Animal MeSH
- Nanofibers therapeutic use MeSH
- Burns MeSH
- Swine MeSH
- Elasticity * MeSH
- Tissue Scaffolds MeSH
- Skin, Artificial * MeSH
- Viscosity MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Nanosecond pulsed electric fields (nsPEFs) applied to cells can induce different biological effects depending on pulse duration and field strength. One known process is the induction of apoptosis whereby nsPEFs are currently investigated as a novel cancer therapy. Another and probably related change is the breakdown of the cytoskeleton. We investigated the elasticity of rat liver epithelial cells WB-F344 in a monolayer using atomic force microscopy (AFM) with respect to the potential of cells to undergo malignant transformation or to develop a potential to metastasize. We found that the elastic modulus of the cells decreased significantly within the first 8 min after treatment with 20 pulses of 100 ns and with a field strength of 20 kV/cm but was still higher than the elasticity of their tumorigenic counterpart WB-ras. AFM measurements and immunofluorescent staining showed that the cellular actin cytoskeleton became reorganized within 5 min. However, both a colony formation assay and a cell migration assay revealed no significant changes after nsPEF treatment, implying that cells seem not to adopt malignant characteristics associated with metastasis formation despite the induced transient changes to elasticity and cytoskeleton that can be observed for up to 1 h.
V zdravej detskej populácii je počas ultrasonografického vyšetrenia (USG) celková echogenita pečeňového parenchýmu porovnateľná s echogenitou kôry obličiek či sleziny. Pri obezite, ako najrizikovejšom faktore vzniku nealkoholovej steatózy pečene (NAFLD non-alcoholic fatty liver disease), môže vzrastať celková echogenita pečene v závislosti od závažnosti steatózy. V súčasnosti sa dostáva do popredia USG kvantifikácia steatózy pečene na základe hodnoty hepatorenálneho indexu (HRI). Hodnota HRI je definovaná pomerom histogramov medzi mediánom echogenity pečene a mediánom echogenity pravej obličky a je priamo úmerná stupňu steatózy pečene, zatiaľ čo celková elasticita pečeňového tkaniva sa môže v prípade rozvinutých štádií steatózy znižovať. V našej práci sme posudzovali význam a možné uplatnenie USG neinvazívnych vyšetrovacích metód na hodnotenie prítomnosti a stupňa steatózy pečene u pediatrických pacientov s exogénnou obezitou. V skupine obéznych detských pacientov bola zaznamenaná vyššia výsledná priemerná hodnota HRI v porovnaní so zdravou kontrolnou skupinou (1,43 ± 0,43 vs. 1,12 ± 0,07; p < 0 ,0001) a nižšia elasticita tkaniva v porovnaní s kontrolnou skupinou (index fibrózy pečene = 1,64 ± 0,43 vs. 1,02 ± 0,27; p < 0,0001). Výsledky našej práce tiež poukazujú na skutočnosť, že pacienti s vyššími hodnotami body mass indexu a obvodu pása majú USG vyšší stupeň steatózy a nižší stupeň elasticity pečene. U obéznych pacientov so zvýšenými hodnotami LDL cholesterolu a triacylglycerolov klesá elasticita pečene a taktiež sa elasticita pečene znižuje so znižujúcou sa sérovou koncentráciou vitamínu D. Na základe prezentovaných dát možno konštatovať, že obezita predstavuje významný rizikový faktor vzniku a rozvoja NAFLD, a že neinvazívne USG hodnotiace metódy majú svoje uplatnenie v diagnostike a kontrole obéznych pacientov s rizikom rozvoja NAFLD.
In healthy children, tissue echogenicity of the liver parenchyma is comparable to that of the kidneys or spleen. With obesity, the most prominent risk factor for non-alcoholic fatty liver disease (NAFLD), overall liver tissue echogenicity increases with the severity of steatosis. Currently, ultrasonographic quantification of liver steatosis using the hepatorenal index (HRI) is coming to the forefront. The HRI value is defined as a histogram ratio between tissue echogenicities of the liver and those of the right kidney, and its increase is proportional to the severity of steatosis, while overall liver tissue elasticity tends to decrease in more advanced stages of steatosis. In this study, we evaluated the significance and possible use of noninvasive ultrasonography for the assessment of the presence and stages of liver steatosis in paediatric patients with exogenous obesity. The obese children cohort showed higher HRI values than the healthy patient group (HRI = 1.43 ± 0.19 vs. 1.12 ± 0.07; p < 0,0001), and lower tissue elasticity than the control group (liver fibrosis index (LFI) = 1.64 ± 0.43 vs. 1.02 ± 0.27). The ultrasonograms also revealed that patients with higher body mass indexes and waist circumferences had more steatosis and lower liver elasticity. Liver elasticity was lower in obese patients with increased serum LDL and triglyceride levels, and the decrease also tended to be proportional to the decrease in serum vitamin D concentration. Based on these results, we conclude that obesity is a significant risk factor for the onset and development of NAFLD, and that noninvasive ultrasonographic methods can be used to diagnose and monitor obese patients with a high risk of NAFLD.
Shear wave imaging is considered to be more precise and less operator dependent when compared with strain imaging. It enables quantitative and reproducible data (Young's modulus of the imaged tissue). However, results of shear wave imaging can be affected by a variety of different factors. The aim of this study is to evaluate the effect of the pressure applied by the ultrasound probe during examination on the measured values of Young's modulus. The effect of the tissue compression on the results of the real-time shear wave elastography was evaluated via the gelatine phantom measurements, via the ex vivo experiments with pig liver, and via the in vivo measurements of the thyroid gland stiffness on healthy volunteers. The results of our measurements confirmed that the measured value of Young's modulus increases with the increasing pressure applied on the imaged object. The highest increase was observed during the ex vivo experiments (400%), and the lowest increase was detected in the case of the phantom measurements (8%). A two- to threefold increase in Young's modulus was observed between the minimum and maximum pressure in the case of the in vivo elastography measurements of thyroid gland. The Veronda-Westman theoretical model was used for the description of the tissue nonlinearity. We conclude that tissue compression by the force exerted on the probe can significantly affect the results of the real-time shear wave elastography measurements. Minimum pressure should be used when measuring the absolute value of Young's modulus of superficial organs.
- MeSH
- Elasticity Imaging Techniques methods MeSH
- Phantoms, Imaging MeSH
- Liver anatomy & histology MeSH
- Humans MeSH
- Mechanical Phenomena * MeSH
- Models, Animal MeSH
- Elastic Modulus MeSH
- Swine MeSH
- Reference Values MeSH
- Thyroid Gland anatomy & histology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Shear wave elastography is a relatively new method of quantitative measurement of tissue elasticity. Assuming that malignant lesions are stiffer than benign ones, elastography may provide supplementary information for their discrimination. However, potential confounding factors impacting tissue stiffness should be investigated first. AIMS: The objective of this study was to measure the stiffness of selected tissues of the head and neck in a normal population and to evaluate its relationship to age, sex, and body mass index. METHODS: Stiffness of the thyroid, submandibular and parotid glands, masseter and sternocleidomastoid muscles, and cervical lymph nodes was measured bilaterally in 128 healthy volunteers (83 female and 45 male). At least 20 subjects in each decade of life (20-29, 30-39‥, 70+) were enrolled. Shear wave elastography was performed by a single radiologist in all the subjects. The stiffnesses obtained were correlated with age, sex, and body mass index. RESULTS: The mean stiffness was 9.5 ± 3.6 kPa for the thyroid, 9.5 ± 4.6 kPa for the lymph node, 11.0 ± 3.4 kPa for the submandibular gland, 9.0 ± 3.5 kPa for the parotid gland, 9.9 ± 4.1 kPa for the sternocleidomastoid, and 10.0 ± 4.3 kPa for the masseter muscle. A slight general decrease in stiffness with increasing age was found. BMI and weight had a small impact on the minimum and maximum stiffness values. The sex of the subject did not affect elasticity. CONCLUSION: The mean stiffness of healthy head and neck organs has a relatively narrow distribution around 11 kPa. The changes of stiffness with age, BMI, and weight that were identified are too small to have clinical impact.
- MeSH
- Biomechanical Phenomena MeSH
- Elasticity Imaging Techniques methods MeSH
- Body Mass Index MeSH
- Neck Muscles diagnostic imaging physiology MeSH
- Humans MeSH
- Parotid Gland diagnostic imaging physiology MeSH
- Predictive Value of Tests MeSH
- Elasticity physiology MeSH
- Reference Values MeSH
- Reproducibility of Results MeSH
- Aging physiology MeSH
- Thyroid Gland diagnostic imaging physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
This investigation studied the effect of concentrated growth factor and nanofat on aging skin of nude mice induced by D-galactose. BALB/c mice were randomly divided into five groups: 5 mice in the control group were fed normally without any intervention, 9 mice were treated with concentrated growth factor (CGF), 9 mice were treated with nanofat (NF), 9 mice were treated with CGF+NF, and 9 mice in the model group (no treatment after subcutaneous injection of D-galactose). Relevant indicators are measured and recorded. In skin and serum, SOD and GSH content in the model group were significantly lower than those in other groups (P<0.05), and the MDA of the three treatment groups was significantly lower than that of the model group (P<0.05). Compared with the control group, the contents of total collagen, type I collagen and type III collagen in the NF group and model group were decreased in different degrees (P<0.05); the contents of elastin and elastic fiber in the skin of nude mice in the model group and NF group were significantly decreased. Compared with the model group, he number of CD31 and VEGF in the treatment group was significantly increased (P<0.01); the skin AGE content of three treatment groups was significantly lower (P<0.05). These findings suggest that concentrated growth factor and nanofat may have a significant effect on delaying aging skin induced by D-galactose in nude mice.
- MeSH
- Platelet Endothelial Cell Adhesion Molecule-1 metabolism MeSH
- Elastin metabolism MeSH
- Galactose pharmacology MeSH
- Glutathione metabolism MeSH
- Collagen metabolism MeSH
- Intercellular Signaling Peptides and Proteins pharmacology MeSH
- Mice, Inbred BALB C MeSH
- Mice, Nude MeSH
- Mice MeSH
- Skin Aging drug effects MeSH
- Superoxide Dismutase metabolism MeSH
- Adipose Tissue transplantation MeSH
- Vascular Endothelial Growth Factor A metabolism MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH