Background: Inherited susceptibility and environmental carcinogens are crucial players in lung cancer etiology, and both exhibit population heterogeneity. MUC16 is overexpressed in various cancers and often associated with poor prognosis. Present work was to investigate the clinical significance of MUC16 in non-small cell lung cancer patients affected by familial lung cancer (FLC) and indoor air pollution caused by coal use. Methods: Clinicopathologic characteristics and MUC16 expression were analyzed and evaluated in our subject population. Vectors were constructed for MUC16 gene knockout and overexpression, then we examined how MUC16 affected lung cancer cell behaviors, including proliferation, migration, invasion and chemoresistance. Results: FLC showed significant association with early-onset (P<0.01) and later stage (P<0.01). Indoor air pollution was associated with younger age (P<0.01), later stage (P<0.05) and AD histology type (P<0.05). Interestingly, two age peaks were observed in our FLC and sporadic group respectively, possibly suggesting multiple major contributors to lung cancer in our subject population. MUC16 overexpression was significantly associated with FLC (P<0.05), indoor air pollution (P<0.01) and later stage (P<0.01), additionally more metastasis cases were observed in patients with up-regulated MUC16 (18.1% vs. 10.3%). Taken together, elevated MUC16 may potentially be one molecular character of FLC in local residents. Intriguingly, patients with more MUC16 up-regulation seemed to have a lower number of white blood cells, especially neutrophils, this reflected MUC16's role in immune regulation. In cell behavior experiments, high MUC16 level could contribute to lung cancer cell proliferation, migration, invasion and chemoresistance, but there were variations among cell lines. Conclusions: MUC16 plays crucial roles in lung cancer pathogenesis, progression and chemoresistance. Interestingly, its association with FLC and indoor air pollution highlights the complexity of lung cancer etiology. Our findings provide useful information to study the intricate interaction between environmental carcinogens and population genetic background.
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Background: Bronchoalveolar lavage (BAL) as complementary method is still used as ancillary tool in diagnosis of interstitial lung diseases. Tobacco smoking has been described to affect the BAL lavage cellular profile. To our knowledge, only few reports have so far investigated CD3+CD4+ and CD3+CD8+ lymphocyte subsets in non-smoking sarcoidosis patients additionally stratified according to CXR stage, and compared them to other non-smoking patients with interstitial lung diseases (ILDs). Methods: We compared lymphocytes immune phenotypes, subsets, with CD3+, CD3+CD4+ and CD3+CD8+ cell markers, in the non-smoking subjects (n=297) including the patients with pulmonary sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) (n=22), hypersensitivity pneumonitis (HP) (n=15), other interstitial idiopathic pneumonias (OIIPs) (n=39). According to prognosis, the patients with S were divided into four groups: 18 patients with Löfgren's syndrome (LS) in chest X-ray (CXR) ≤1 stage, 64 patients without LS in CXR ≤1 stage, 113 patients in CXR 2 stage and 26 patients with advanced CXR ≥3 stage. Results: After the use of false discovery rate (FDR) correction, relative numbers (%) of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD4/CD3+CD8 ratio showed the most significant differences between the non-smokers with S (both with/without LS) and the non-smokers with other ILDs (IPF, OIIPs, HP). These lymphocytes subsets were further altered in the non-smokers with CXR stage 2 compared to the non-smokers with other ILDs (IPF, OIIPs, HP). We did not observe any differences in these lymphocyte subsets and CD3+CD4+/CD3+CD8+ ratio between the non-smokers with advanced sarcoidosis stage (CXR ≥3) and the non-smokers with IPF. Conclusions: Our data on the non-smokers confirmed the presence of the typical BAL cellular profile in sarcoidosis. The BAL cellular profile was helpful namely for differentiation of less advanced sarcoidosis. Its definite diagnostic utility should be the subject of further clinical studies with large numbers of the well characterized patients taking into consideration other clinical factors influencing BAL cellular profile, such as smoking or treatment.
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Background: In a three-month report from the CGA-TAVI registry, we found the Multidimensional Prognostic Index (MPI) and Short Physical Performance Battery (SPPB) to be of value for predicting short-term outcomes in elderly patients undergoing transcatheter aortic valve implantation (TAVI). In the present analysis, we examined the association of these tools with outcomes up to one year post-TAVI. Methods: CGA-TAVI is an international, observational registry of geriatric patients undergoing TAVI. Patients were assessed using the MPI and SPPB. Efficacy of baseline values and any postoperative change for predicting outcome were established using logistic regression. Kaplan-Meier analysis was carried out for each comprehensive geriatric assessment tool, with survival stratified by risk category. Results: One year after TAVI, 14.1% of patients deceased, while 17.4% met the combined endpoint of death and/or non-fatal stroke, and 37.7% the combined endpoint of death and/or hospitalisation and/or non-fatal stroke. A high-risk MPI score was associated with an increased risk of all-cause mortality (aOR = 36.13, 95% CI: 2.77-470.78, P = 0.006) and death and/or non-fatal stroke (aOR = 10.10, 95% CI: 1.48-68.75, P = 0.018). No significant associations were found between a high-risk SPPB score and mortality or two main combined endpoints. In contrast to a worsening SPPB, an aggravating MPI score at three months post-TAVI was associated with an increased risk of death and/or non-fatal stoke at one year (aOR = 95.16, 95% CI: 3.41-2657.01). Conclusions: The MPI showed value for predicting the likelihood of death and a combination of death and/or non-fatal stroke by one year after TAVI in elderly patients.
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Cancer and cardiovascular diseases have been classified as non-communicable diseases for decades. Both diseases have characteristics of immune reactions, which are principally identical, but differing in important aspects. The aim of this communication is to highlight new approaches to immune processes involved in both types of diseases.
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OBJECTIVE: To describe the sonographic characteristics of a lymphocele after pelvic and/or paraaortic lymphadenectomy for gynecological malignancy, analyze and identify ultrasound characteristics related to the symptomatic and asymptomatic lymphoceles. MATERIALS AND METHODS: This is a retrospective analysis of ultrasound examination data collected consecutively in patients after pelvic and/or paraaortic lymphadenectomy in one institution. We recorded the number of lymphoceles, localization, size; ultrasound morphology following International Ovarian Tumor Analysis group classification and symptoms. RESULTS: We described and analyzed 227 lymphoceles (150 asymptomatic and 77 symptomatic) in 161 patients. The asymptomatic lymphocele is typically a thick-walled cystic lesion without vascularization, round and unilocular with anechoic or ground-glass content. The symptomatic lymphocele is typically an oval, or ovoid, unilocular lesion with low-level or anechoic content (ground glass content is unlikely to be present, p < 0.001) and the presence of debris and septations. The lymphocele size (p = 0.001), number of lymphoceles (>1) (p = 0.005), septa (p = 0.002), and debris (p < 0.001) were independent ultrasound features correlating to symptoms development. More than one lymphocele (p = 0.047), septations (p = 0.007) and presence of debris (p < 0.001) were independent ultrasound features correlated to infection. CONCLUSION: Ultrasound features of symptomatic and asymptomatic lymphocele differ. The clues for lymphocele differential diagnosis are the history of lymphadenectomy and the finding cystic lesion with typically ultrasound features of lymphocele, adjacent to great pelvic vessels. Unique ultrasound features of lymphocele may help to distinguish from tumor relapse, hematoma, abscess, seroma or urinoma.
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- asymptomatické nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- lymfadenektomie statistika a číselné údaje MeSH
- lymfokela diagnostické zobrazování patologie MeSH
- nádory ženských pohlavních orgánů chirurgie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- ultrasonografie * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
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Neurologic symptoms in Wilson disease (WD) appear at an older age compared to hepatic symptoms and manifest in patients with misdiagnosed liver disease, in patients when the hepatic stage is clinically silent, in the case of non-compliance with anti-copper treatment, or with treatment failure. Neurologic symptoms in WD are caused by nervous tissue damage that is primarily a consequence of extrahepatic copper toxicity. Copper levels in brain tissues as well as cerebrospinal fluid (CSF) are diffusely increased by a factor of 10 and its toxicity involves various mechanisms such as mitochondrial toxicity, oxidative stress, cell membrane damage, crosslinking of DNA, and inhibition of enzymes. Excess copper is initially taken-up and buffered by astrocytes and oligodendrocytes but ultimately causes dysfunction of blood-brain-barrier and demyelination. Most severe neuropathologic abnormalities, including tissue rarefaction, reactive astrogliosis, myelin palor, and presence of iron-laden macrophages, are typically present in the putamen while other basal ganglia, thalami, and brainstem are usually less affected. The most common neurologic symptoms of WD are movement disorders including tremor, dystonia, parkinsonism, ataxia and chorea which are associated with dysphagia, dysarthria and drooling. Patients usually manifest with various combinations of these symptoms while purely monosymptomatic presentation is rare. Neurologic symptoms are largely reversible with anti-copper treatment, but a significant number of patients are left with residual impairment. The approach for symptomatic treatment in WD is based on guidelines for management of common movement disorders. The vast majority of WD patients with neurologic symptoms have abnormalities on brain magnetic resonance imaging (MRI). Pathologic MRI changes include T2 hyperintensities in the basal ganglia, thalami and white matter, T2 hypointensities in the basal ganglia, and atrophy. Most importantly, brain damage and neurologic symptoms can be prevented with an early initiation of anti-copper treatment. Introducing population WD screening, e.g., by exome sequencing genetic methods, would allow early treatment and decrease the neurologic burden of WD.
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A reflection on the measure of fluorescence specificity of indocyanine green (ICG) in non-intubated pulmonary segmentectomy.
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Purpose: The aim of this study was to investigate the influence of the cardiorespiratory fitness level on the response to high-intensity interval training (HIIT) with an individually adjusted running speed of the same relative intensity. The evaluation focused on acute cardiorespiratory response, postexercise cardiac autonomic modulation (heart rate variability (HRV)) and biochemical markers of inflammation, oxidative stress, and muscle damage. Methods: Thirty participants were divided into 3 subgroups: well trained, moderately trained, and untrained. All the participants performed 30 min HIIT composed of 6 × 2 min interval exercise with work-to-relief ratio = 1 and work intensity 100% of individual velocity at maximal oxygen consumption (VO2max ). Acute cardiorespiratory variables, postexercise HRV, lactate, interleukin-6 (IL-6), total antioxidant capacity (TAC), creatine kinase, and myoglobin up to 4 h after HIIT were monitored. Results: The differences in relatively expressed cardiorespiratory variables (heart rate, VO2) during HIIT were at most moderate, with the most pronounced between-group differences in absolute VO2 values. The disruption of the postexercise HRV was the most pronounced in untrained individuals, and this difference persisted 1 h after HIIT. The highest postexercise IL-6 and TAC concentrations and the lowest changes in creatine kinase and myoglobin were revealed in well-trained individuals. Conclusion: The higher fitness level was associated with the less pronounced postexercise cardiac autonomic changes and their faster restoration, even when there were similar acute cardiorespiratory responses. These findings were simultaneously accompanied by the higher postexercise IL-6 and TAC concentrations and less significant changes in muscle damage biochemical markers in well-trained individuals.
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Background: The novel HeartMate 3 (Abbott, Chicago, IL, USA) left ventricular assist device (LVAD) was worldwide first implanted by Prof. Schmitto and his team in 2014 at the Hannover Medical School, Germany and received CE Mark approval in October, 2015 following completion of a clinical trial. Methods: Although HeartMate 3 implantation in the clinical trial was restricted to conventional sternotomy, the small size of the pump allows for less-invasive implantation, generally associated with less trauma and reduced perioperative complication rates. Herein we describe our first experiences with a less-invasive implantation of the HeartMate 3 using an upper hemi-sternotomy combined with anterior lateral thoracotomy approach. Results: Results demonstrate the feasibility of this novel, less invasive technique for HeartMate 3 LVAD implantation with diminished surgical trauma, less postoperative bleeding, maintenance of the chest stability, reduced need of blood product transfusion and earlier recovery. Conclusions: The results of our study indicate that less-invasive implantation of the HeartMate 3 is technically feasible and offers several benefits for surgical outcome and may become the standard of care for LVAD implantation techniques.
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