PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• MeSH
• brachyterapie * metody   MeSH
• celková dávka radioterapie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory úst * radioterapie   patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0-42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.

• MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• hepatolentikulární degenerace * patologie   diagnostické zobrazování   MeSH
• játra patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

• MeSH
• analýza mediace * MeSH
• dospělí MeSH
• kouření * epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• nádory plic * epidemiologie   MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• senioři MeSH
• společenská třída * MeSH
• studie případů a kontrol MeSH
• zkreslení výsledků (epidemiologie) * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

• MeSH
• dieta MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• index tělesné hmotnosti MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   epidemiologie   MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• pití alkoholu MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

• MeSH
• autofagie * genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom slinivky břišní * genetika   patologie   MeSH
• forkhead transkripční faktory MeSH
• genetická predispozice k nemoci * MeSH
• hepatocytární jaderný faktor 3-alfa genetika   metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

• MeSH
• biologické markery * krev   MeSH
• claudin-3 * metabolismus   MeSH
• dospělí MeSH
• funkce střevní bariéry MeSH
• lidé středního věku MeSH
• lidé MeSH
• permeabilita * MeSH
• proteiny vázající mastné kyseliny * krev   MeSH
• roztroušená skleróza * patofyziologie   metabolismus   krev   MeSH
• střevní sliznice metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Asymmetric or unilateral hearing loss (AHL) may cause irreversible changes in the processing of acoustic signals in the auditory system. We aim to provide a comprehensive view of the auditory processing abilities for subjects with acquired AHL, and to examine the influence of AHL on speech perception under difficult conditions, and on auditory temporal and intensity processing. DESIGN: We examined peripheral and central auditory functions for 25 subjects with AHL resulting from vestibular schwannoma, and compared them to those from 24 normal-hearing controls that were matched with the AHL subjects in mean age and hearing thresholds in the healthy ear. Besides the basic hearing threshold assessment, the tests comprised the detection of tones and gaps in a continuous noise, comprehension of speech in babble noise, binaural interactions, difference limen of intensity, and detection of frequency modulation. For the AHL subjects, the selected tests were performed separately for the healthy and diseased ear. RESULTS: We observed that binaural speech comprehension, gap detection, and frequency modulation detection abilities were dominated by the healthy ear and were comparable for both groups. The AHL subjects were less sensitive to interaural delays, however, they exhibited a higher sensitivity to sound level, as indicated by lower difference limen of intensity and a higher sensitivity to interaural intensity difference. Correlations between the individual test scores indicated that speech comprehension by the AHL subjects was associated with different auditory processing mechanisms than for the control subjects. CONCLUSIONS: The data suggest that AHL influences both peripheral and central auditory processing abilities and that speech comprehension under difficult conditions relies on different mechanisms for the AHL subjects than for normal-hearing controls.

• MeSH
• dospělí MeSH
• jednostranná nedoslýchavost * patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• percepce řeči * fyziologie   MeSH
• senioři MeSH
• sluchová percepce fyziologie   MeSH
• sluchový práh * MeSH
• studie případů a kontrol MeSH
• vestibulární schwannom * patofyziologie   komplikace   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

• MeSH
• dárci tkání statistika a číselné údaje   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• perfuze * metody   přístrojové vybavení   MeSH
• přežívání štěpu * MeSH
• senioři MeSH
• terapeutická hypotermie metody   MeSH
• transplantace jater * metody   škodlivé účinky   MeSH
• uchovávání orgánů * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Cíl: Fénixin má endoteliální ochranné a protizánětlivé vlastnosti a je spojován s rozvojem hypertenze. Vzhledem k tomu, že endoteliální dysfunkce hrají významnou roli v patofyziologii preeklampsie, zaměřili jsme se na vyšetření sérových hladin fénixinu-14 a fénixinu-20 u těhotných žen s diagnostikovanou preeklampsií. Materiál a metody: V této průřezové případové studii tvořilo 45 těhotných žen s diagnostikovanou preeklampsií skupinu preeklampsie, zatímco 45 zdravých těhotných žen, které odpovídaly skupině preeklampsie věkem, indexem tělesné hmotnosti a gestačním věkem plodu, sloužilo jako kontrolní skupina. Pro analýzu hladin fénixinu-14 a fénixinu-20 ve vzorcích séra byly použity komerční soupravy. Výsledky: Bylo zjištěno, že ve skupině s preeklampsií byla hladina fénixinu-14 v séru 390,3 pg/ml, zatímco v kontrolní skupině byla 393,2 pg/ml (p = 0,434). Hladina fénixinu-20 v séru ve skupině s preeklampsií byla 346,6 pg/ml a v kontrolní skupině 379,9 pg/ml (p = 0,278). Když byla skupina s preeklampsií rozdělena do podskupin podle závažnosti onemocnění a počátku onemocnění a porovnána s kontrolní skupinou, v hladinách sérového fénixinu-14 a fénixinu-20 mezi skupinami nebyl nalezen žádný významný rozdíl. Závěr: V této studii byly sérové hladiny fénixinu-14 a fénixinu-20 u preeklampsie a u kontrolní skupiny podobné. Ačkoli je velikost vzorku příliš malá na to, aby bylo možné vyvodit definitivní závěr, zjištění naznačují, že fénixin-14 ani fénixin-20 v patofyziologii preeklampsie nehraje roli.

Objective: Phoenixin has endothelial protective and anti-inflammatory properties, but has been associated with the development of hypertension. Given that endothelial dysfunction plays a significant role in the pathophysiology of preeclampsia, we aimed to investigate the serum levels of phoenixin-14 and phoenixin-20 in pregnant women diagnosed with preeclampsia. Materials and methods: In this cross-sectional case-control study, 45 pregnant women diagnosed with preeclampsia comprised the preeclampsia group, while 45 healthy pregnant women, matched to the preeclampsia group by age, body mass index, and gestational age, served as the control group. Commercial kits were used to analyze phoenixin-14 and phoenixin-20 levels in serum samples. Results: Serum phoenixin-14 level was 390.3 pg/mL in the preeclampsia group and 393.2 pg/mL in the control group (P = 0.434). While the serum phoenixin-20 level was 346.6 pg/mL in the preeclampsia group, it was 379.9 pg/mL in the control group (P = 0.278). When the preeclampsia group was divided into subgroups according to the severity of the disease and the onset of the disease and compared with the control group, no significant difference was found between the groups regarding serum phoenixin-14 and phoenixin-20 levels. Conclusion: In this study, serum levels of phoenixin-14 and phoenixin-20 were similar in both the preeclampsia and control groups. Although the sample size is too small to draw a definitive conclusion, findings suggest that phoenixin-14 and phoenixin-20 do not play a role in the pathophysiology of preeclampsia.

There is increasing pressure on meat producers worldwide due to the need for higher yields and improved meat quality. This is why anabolic androgenic steroids (AAS) have been widely used in most countries, due to their ability to accelerate animal muscle growth. However, out of concern for their side effects, EU states have banned their use and implemented control mechanisms. But they are reaching their limits, and therefore, it is necessary to look for new ways and investigate the mechanism of action of AAS on muscle tissue. This study replicated the administration of banned AAS (testosterone, nandrolone and their combination) and observed their effect on pig muscle. The pig model was purposely chosen for the study, as no such research has been carried out on this species. At the same time, pork is one of the most consumed meats in Europe. It focused on histological changes in muscle structure, specifically the size of muscle fibres and the number of satellite cells per muscle fibre. Furthermore, ultrastructural changes in muscle fibres, the diameter of myofibrils, the number of myofibrils per area, the distance between myofibrils and the size of sarcomeres were examined. The results using the techniques of histology, fluorescent labelling and transmission electron microscopy showed that, after the application of AAS, there is an increase in the diameter of muscle fibres, an increase in the diameter of myofibrils, a decrease in the number of myofibrils per surface area and, in the case of testosterone, an increase in the distance between myofibrils and an increase in the length of sarcomeres. There was also a significant increase in the number of satellite cells per muscle fibre. The detected statistically significant differences between control and experimental groups provide evidence that selected histological parameters could be additional mechanisms for detecting the presence of AAS in pork meat in the future.

• MeSH
• anabolika * farmakologie   MeSH
• kosterní svalová vlákna * účinky léků   ultrastruktura   MeSH
• kosterní svaly účinky léků   anatomie a histologie   ultrastruktura   MeSH
• myofibrily * účinky léků   ultrastruktura   MeSH
• nandrolon * farmakologie   MeSH
• prasata anatomie a histologie   MeSH
• sarkomery účinky léků   ultrastruktura   MeSH
• satelitní buňky kosterního svalu účinky léků   ultrastruktura   MeSH
• testosteron * farmakologie   MeSH
• transmisní elektronová mikroskopie veterinární   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH