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1.
Pediatr Res ; 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33339964

RESUMO

BACKGROUND: Thrombelastometry, allowing timely assessment of global hemostatic function, is increasingly used to guide hemostatic interventions in bleeding patients. Reference values are available for adults and children, including infants but not neonates immediately after birth. METHODS: Neonates were grouped as preterm (30 + 0 to 36 + 6 weeks/days) and term (37 + 0 to 39 + 6 weeks/days). Blood samples were drawn from the umbilical cord immediately after cesarean section and analyzed by thrombelastometry. Reference ranges were determined for the extrinsic and intrinsic coagulation pathways, fibrin polymerization, and hyperfibrinolysis detection. RESULTS: All extrinsically activated test parameters, but maximum lysis (P = 0.139) differed significantly between both groups (P ≤ 0.001). Maximum clot firmness in the fibrin polymerization test was comparable (P = 0.141). All intrinsically activated test parameters other than coagulation time (P = 0.537) and maximum lysis (P = 0.888) differed significantly (P < 0.001), and so did all aprotinin-related test parameters (P ≤ 0.001) but maximum lysis (P = 0.851). CONCLUSIONS: This is the first study to identify reference ranges for thrombelastometry in preterm and term neonates immediately after birth. We also report differences in clot initiation and clot strength in neonates born <37 versus ≤40 weeks of gestation, mirroring developmental hemostasis. IMPACT: Impact: This prospective observational study is the first to present reference ranges in preterm and term infants for all types of commercially available tests of thrombelastometry, notably also including the fibrin polymerization test. IMPORTANCE: Viscoelastic coagulation assays such as thrombelastometry have become integral to the management of perioperative bleeding by present-day standards. Reference values are available for adults, children, and infants but not for neonates. Key message: Clot initiation and formation was faster and clot strength higher in the term than in the preterm group. Parameters of thrombelastometry obtained from cord blood do not apply interchangeably to preterm and term neonates.

2.
JNCI Cancer Spectr ; 4(5): pkaa051, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33134831

RESUMO

Background: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. Methods: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. Results: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. Conclusions: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.

3.
Am J Sports Med ; 48(9): 2151-2160, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543880

RESUMO

BACKGROUND: Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. HYPOTHESIS: Zoledronic acid improves bone mineral density of the humeral head and biomechanical properties of the enthesis after reconstruction of chronic rotator cuff tears in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 32 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy with delayed transosseous rotator cuff reconstruction after 3 weeks. All rats were sacrificed 8 weeks after rotator cuff repair. Animals were randomly assigned to 1 of 2 groups. At 1 day after rotator cuff reconstruction, the intervention group was treated with a single subcutaneous dose of zoledronic acid at 100 µg/kg bodyweight, and the control group received 1 mL of subcutaneous saline solution. In 12 animals of each group, micro-computed tomography scans of both shoulders were performed as well as biomechanical testing of the supraspinatus enthesis of both sides. In 4 animals of each group, histological analyses were conducted. RESULTS: In the intervention group, bone volume fraction (bone volume/total volume [BV/TV]) of the operated side was higher at the lateral humeral head (P = .005) and the medial humeral head (P = .010) compared with the control group. Trabecular number on the operated side was higher at the lateral humeral head (P = .004) and the medial humeral head (P = .001) in the intervention group. Maximum load to failure rates on the operated side were higher in the intervention group (P < .001). Cortical thickness positively correlated with higher maximum load to failure rates in the intervention group (r = 0.69; P = .026). Histological assessment revealed increased bone formation in the intervention group. CONCLUSION: Single-dose therapy of zoledronic acid provided an improvement of bone microarchitecture at the humeral head as well as an increase of maximum load to failure rates after transosseous reconstruction of chronic rotator cuff lesions in rats. CLINICAL RELEVANCE: Zoledronic acid improves bone microarchitecture as well as biomechanical properties after reconstruction of chronic rotator cuff tears in rodents. These results need to be verified in clinical investigations.


Assuntos
Densidade Óssea , Lesões do Manguito Rotador , Manguito Rotador , Ácido Zoledrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Cicatrização , Microtomografia por Raio-X
4.
PLoS One ; 15(4): e0232099, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32330183

RESUMO

Food cues affect hunger and nutritional choices. Omnipresent stimulation with palatable food contributes to the epidemics of obesity. The objective of the study was to investigate the impact of food cues on appetite-related hormones and to assess the functionality of the secreted hormones on macronutrient uptake in healthy subjects. Additionally, we aimed at verifying differences in the response of total and active ghrelin to stimulation with food pictures and to a meal followed by the stimulation. We were also interested in the identification of factors contributing to response to food cues. We recruited healthy, non-obese participants for two independent cross-over studies. During the first study, the subjects were presented random non-food pictures on the first day and pictures of foods on the second day of the study. Throughout the second study, following the picture session, the participants were additionally asked to drink a milkshake. Concentrations of blood glucose, triglycerides and hunger-related hormones were measured. The results showed that concentrations of several hormones measured in the blood are interdependent. In the case of ghrelin and gastric inhibitory peptide (GIP) as well as ghrelin and glucagon-like peptide-1 (GLP-1), this co-occurrence relies on the visual cues. Regulation of total ghrelin concentration following food stimulation is highly individual and responders showed upregulated total ghrelin, while the concentration of active ghrelin decreases following a meal. Protein content and colour intensity of food pictures reversely correlated with participants' rating of the pictures. We conclude that observation of food pictures influences the concentration of several appetite-related hormones. The close link of visual clues to physiological responses is likely of clinical relevance. Additionally, the protein content of displayed foods and green colour intensity in pictures may serve as a predictor of subjective attractiveness of the presented meal.


Assuntos
Fome/fisiologia , Obesidade/psicologia , Estimulação Luminosa/métodos , Adolescente , Adulto , Apetite/fisiologia , Glicemia/metabolismo , Comportamento de Escolha/fisiologia , Sinais (Psicologia) , Comportamento Alimentar/fisiologia , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Nutrientes , Peptídeo YY/sangue
5.
Mutagenesis ; 35(3): 283-290, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32255470

RESUMO

Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.

6.
Wien Klin Wochenschr ; 132(7-8): 216, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016509

RESUMO

Correction to: Wien Klin Wochenschr 2019 https://doi.org/10.1007/s00508-019-01595-8 The original version of this article unfortunately contained a mistake. The last sentence should read: Patients with ALD had significantly lower sclerostin levels, compared to controls. The authors apologize for the ….

7.
Artif Organs ; 44(6): 638-646, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31951030

RESUMO

Extracorporeal membrane oxygenation (ECMO) is gaining importance in the perioperative management of lung transplant patients. To date, the ideal substance for anticoagulation of ECMO patients is still a matter of debate. In this study, we describe our experience with the use of low molecular weight heparin (LMWH) in comparison with unfractioned heparin (UFH) in lung transplant patients undergoing perioperative ECMO support. We retrospectively analyzed data from all lung transplant patients who underwent perioperative ECMO support at our institution between 2013 and 2017. Bleeding events served as primary outcome parameter. Secondary outcome parameters consisted of thromboembolic events. 102 patients were included in this study, of which 22 (21.6%) received UFH for anticoagulation, and 80 (78.4%) received LMWH. There was no difference between the two groups in regard to serious bleeding events (22.7% in the UFH group vs 12.5% in the LMWH group, P = .31). However, the proportion of patients experiencing thromboembolic events was significantly higher in the UFH group than in the LMWH group (50% vs 20%, P = .01). After adjusting for baseline differences between the two groups, we still observed a difference with respect to thromboembolic events. These data remain to be validated in future prospective, randomized trials.

8.
Wien Klin Wochenschr ; 132(1-2): 19-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31912287

RESUMO

BACKGROUND: Patients with hepatic cirrhosis are at increased risk of bone loss. Recent work on areal bone mineral density has reported contradictory findings. As the assessment of bone microarchitecture is complex, a search was made for correlations with new serum markers of bone turnover. Current data on serum sclerostin levels in patients with increased fracture risk are divergent and to date only one study has examined patients with hepatic cirrhosis. Therefore, the aim of this study was to evaluate serum sclerostin levels and to test for correlations with microarchitecture. METHODS: This study was performed in 32 patients with recently diagnosed hepatic cirrhosis and 32 controls. The parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Sclerostin was detected via a new ELISA that detects the active receptor interaction site at loop 2 of the sclerostin core region. RESULTS: Sclerostin levels were slightly, but not significantly lower in the patient group, compared to controls. In contrast, patients with alcoholic liver cirrhosis had significantly lower levels than the controls. A significant correlation with areal bone mineral density (BMD) and trabecular microarchitecture was observed in the patient group. However, there was hardly any correlation between sclerostin and bone microarchitecture in the controls. CONCLUSION: In hepatic cirrhosis, sclerostin is related to altered bone microarchitecture and lower areal BMD. In alcoholic liver disease, low sclerostin concentrations were seen.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Biomarcadores , Densidade Óssea , Remodelação Óssea , Cirrose Hepática , Proteínas Adaptadoras de Transdução de Sinal/sangue , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações
9.
Eur J Trauma Emerg Surg ; 46(5): 1151-1158, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30747275

RESUMO

INTRODUCTION: Multiple fractures are of high clinical relevance, as a significant increase in mortality rate has been described. The purpose of this study was to evaluate differences in age and gender distribution in multiple fractures dependent on severity of trauma. Furthermore, affected anatomic regions and frequently associated fracture regions were investigated. METHODS: Patients who had sustained multiple fractures between 2000 and 2012 were included in this study. At hospital admission, patients were divided according to trauma severity (high- vs low-traumatic), gender, and age for demographic analysis. Fractures were grouped in anatomical regions, and multiple fracture event probabilities as well as frequently associated regions were calculated. RESULTS: In total, 25,043 patients at an age range of 0-100 years (5.8% of all fracture patients; 14,769 male and 10,274 female patients) who sustained 57,862 multiple fractures were included. The lumbar/thoracic spine, cervical spine, femoral shaft, skull, and pelvis showed a probability of more than 40% of the presence of further fractures in each high-traumatic fracture event. In high-traumatic fracture events, male patients were more affected (p < 0.001). Considering low-traumatic fractures, female patients had a significantly higher proportion (p < 0.001) of multiple fractures among all fractures than male patients. CONCLUSIONS: As a novelty, gender as well as age distributions in multiple fracture patients and a probability statement with the most affected anatomic regions, the risk of presence of further fractures for every region, and the frequently associated fracture regions including the percentage of occurrence are provided. These aspects yield new opportunities for clinical work and may reduce the high rate of overlooked fractures stated in the literature.

10.
Int J Cancer ; 146(12): 3256-3266, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31495913

RESUMO

Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (pFDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (pFDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.

11.
J Orthop Res ; 37(12): 2516-2523, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31410876

RESUMO

Bone stress injuries are commonly due to repetitive loading, as often described in competitive athletes or military recruits. The underlying pathophysiology of bone stress injuries is multifactorial. The present cross-sectional study investigated (i) cortical and trabecular bone microstructure as well as volumetric bone mineral density in subjects with bone stress injuries at the tibial diaphysis, measured at the distal tibia and the distal radius by means of high-resolution peripheral quantitative computed tomography (CT), (ii) areal bone mineral density using dual-energy X-ray absorptiometry as well as calcaneal dual X-ray absorptiometry and laser, and (iii) the influence on bone turnover markers of formation and resorption at the early phase after injury. A total of 26 Caucasian male professional soldiers with post-training bone stress injury at the tibial diaphysis were included (case group). A total of 50 male, Caucasian professional soldiers from the same military institution served as controls (control group). High-resolution peripheral quantitative CT revealed a higher total area at the radius within the case group. Cortical bone mineral density was reduced at the radius and tibia within the case group. The trabecular number and trabecular thickness were reduced at the tibia in the case group. The trabecular network was more inhomogeneous at the radius and tibia within the case group. Calcaneal dual X-ray absorptiometry and laser was significantly reduced in the case group. This study quantified differences in bone microstructure among otherwise healthy individuals. Differences in bone microarchitecture may impair the biomechanical properties by increasing the susceptibility to sustain bone stress injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2516-2523, 2019.


Assuntos
Densidade Óssea , Fraturas de Estresse/etiologia , Militares , Absorciometria de Fóton , Adulto , Estudos Transversais , Fraturas de Estresse/diagnóstico por imagem , Humanos , Masculino , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Ann Surg ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425286

RESUMO

OBJECTIVE: The aim of this study was to determine the clinical role of the systemic immune-inflammation index in patients with resectable adenocarcinoma of the gastroesophageal junction treated with or without neoadjuvant therapy. BACKGROUND: Adenocarcinoma of the gastroesophageal junction is an aggressive disease, with less than 20% of overall patients surviving more than 5 years after diagnosis, while currently available clinical staging for esophageal cancer is lacking necessary accuracy. The systemic immune-inflammation index (SII) based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in various malignancies. METHODS: Data of consecutive patients undergoing esophagectomy (n = 320, 1992 to 2016) were abstracted. The cut point for high and low SII before neoadjuvant treatment and before surgery was calculated for illustration of the Kaplan-Meier curves. SII was used for the correlation with patients' clinicopathological characteristics as a continuous variable. Survival was analyzed with Cox proportional hazards models using clinical or pathological staging, adjusting for other known survival predictors. RESULTS: In both neoadjuvantly treated and primarily resected patients, high SII was significantly associated with diminished overall [hazard ratio (HR) 1.3, 95% confidence interval (95% CI) 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively] and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively). In multivariable survival analysis, SII remained an independent prognostic factor for overall survival (HR 1.3, 95% CI 1.2-1.4; HR 1.2, 95% CI 1.2-1.3, respectively) and disease-free survival (HR 1.3, 95% CI 1.2-1.3; HR 1.2, 95% CI 1.2-1.3, respectively) in primarily resected and neoadjuvantly treated patients. CONCLUSION: Elevated SII is an independent adverse prognostic factor in patients with resectable gastroesophageal adenocarcinomas with and without neoadjuvant treatment.

13.
Int J Cancer ; 145(5): 1221-1231, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30665271

RESUMO

Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.


Assuntos
Neoplasias Colorretais/sangue , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade
14.
Oncoimmunology ; 7(6): e1435226, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29872575

RESUMO

Background. The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients. Methods. 168 patients who underwent esophagectomy because of AEG between 1992-2011 were included in this study. PD-L1, PD-L2 and PD-1 expression were evaluated by immunohistochemistry and correlated with various clinicopathological parameters, disease-free survival (DFS) and long-term overall survival (OS). Results. PD-L1 expression by cancer-cells (cancer-cell-PD-L1+) was found in 43.5% of patients whereas PD-L1 expression by TILs (TILs-PD-L1+) was observed in 69%. PD-L2 expression by cancer-cells and TILs was only found in 3.5% and 1.8%, respectively. Additionally, 77.4% of tumors contained PD-1+-cancer-cells and 81% PD-1+-TILs. Patients with increased expression of PD-1 by cancer-cells and TILs showed significantly reduced OS and DFS, as determined by univariate, but not multivariate analysis. Expression of PD-L1 by cancer-cells was found to be an independent predictor for improved DFS (p = 0.038) and OS (p = 0.042) in multivariate analysis. Conclusions. Cancer cells and TILs displayed PD-L1 expression in around 50% and PD-1 expression in around 80% of tumor-biospecimens obtained from AEG patients. Expression of PD-L1 is an independent predictor of favorable outcome in AEG, whereas PD-1 expression is associated with worse outcome and advanced tumor stage.

15.
Oncotarget ; 9(17): 13582-13592, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29568379

RESUMO

Considering the high prevalence of colorectal cancer (CRC) and relatively high mortality there is strong interest in identification of clinically relevant biomarkers. Telomere shortening is supposed to contribute to genomic instability and crucially involved in process of carcinogenesis. Peripheral blood leukocyte (PBL) telomere length was previously investigated in several studies as potential biomarker for CRC but with controversial results. This prompted us to investigate relative PBL telomere length in association with different histological findings throughout the continuum of colorectal carcinogenesis in order to reflect the whole spectrum of putative CRC development in a large study involving 2011 individuals. The study based on the Colorectal Cancer Study of Austria (CORSA), including 384 CRC cases as well as age- and gender-matched 544 high-risk adenomas, 537 low-risk adenoma patients and 546 colonoscopy-negative controls. Relative expression of telomeric repeats and the single copy reference gene, albumin (T/S ratio) was determined using monochrome multiplex quantitative PCR (MMQPCR). Telomeres were found to be significantly longer in CRC patients compared to control subjects (P = 3.61x10-6). Yet, no significant differences in telomere length could be detected for high-risk (P = 0.05956) and low-risk colorectal adenoma patients (P = 0.05224). In addition, results presented in this manuscript highlight the impact of various epidemiological factors on PBL telomere length and its involvement in CRC. However, further large studies also including colorectal adenomas are necessary to confirm these results.

16.
Sci Rep ; 8(1): 4867, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29559644

RESUMO

The assessment of bone quality and the prediction of fracture risk in idiopathic osteoporosis (IOP) are complex prospects as bone mineral density (BMD) and bone turnover markers (BTM) do not indicate fracture-risk. MicroRNAs (miRNAs) are promising new biomarkers for bone diseases, but the current understanding of the biological information contained in the variability of miRNAs is limited. Here, we investigated the association between serum-levels of 19 miRNA biomarkers of idiopathic osteoporosis to bone microstructure and bone histomorphometry based upon bone biopsies and µCT (9.3 µm) scans from 36 patients. Four miRNAs were found to be correlated to bone microarchitecture and seven miRNAs to dynamic histomorphometry (p < 0.05). Three miRNAs, namely, miR-29b-3p, miR-324-3p, and miR-550a-3p showed significant correlations to histomorphometric parameters of bone formation as well as microstructure parameters. miR-29b-3p and miR-324-p were found to be reduced in patients undergoing anti-resorptive therapy. This is the first study to report that serum levels of bone-related miRNAs might be surrogates of dynamic histomorphometry and potentially reveal changes in bone microstructure. Although these findings enhance the potential value of circulating miRNAs as bone biomarkers, further experimental studies are required to qualify the clinical utility of miRNAs to reflect dynamic changes in bone formation and microstructure.


Assuntos
Osso e Ossos/patologia , Osteoporose Pós-Menopausa/genética , Osteoporose/genética , Adulto , Biomarcadores/sangue , Densidade Óssea/genética , Osso e Ossos/metabolismo , Osso e Ossos/ultraestrutura , MicroRNA Circulante/análise , MicroRNA Circulante/genética , Estudos Transversais , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/fisiologia , Pessoa de Meia-Idade , Osteogênese/genética , Osteogênese/fisiologia , Osteoporose/sangue , Osteoporose/metabolismo , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/metabolismo , Fraturas por Osteoporose/genética , Fatores de Risco
17.
Oncotarget ; 9(6): 6968-6976, 2018 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-29467943

RESUMO

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients' characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3-89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS.

18.
J Knee Surg ; 31(5): 467-471, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28701006

RESUMO

The primary objective was to compare the intraoperative data assessed by OrthoPilot (Aesculap AG, Tuttlingen, Germany) with postoperative coronal and sagittal long-leg standing radiographs. The secondary objective was to evaluate the influence of sex and body mass index (BMI) on the accuracy and effectiveness of the implantation of the knee prosthesis by OrthoPilot. We included 75 patients in our investigation. Participants received an e.motion (Aesculap AG) knee prosthesis using the OrthoPilot navigation system. Postoperative long-leg standing anteroposterior and lateral radiographs were performed. We compared the intraoperative navigational data with postoperative determined angles of knee geometry. We also compared the sex and BMI of participants to their difference between intraoperative and postoperative measurements to test for an association. We found a difference between intraoperative data and radiographs of 1.8 degrees for the hip-knee-ankle angle. The intraoperative lateral distal femoral angle and medial proximal tibial angle differed from the radiological analysis by 1.2 degrees, respectively. The lateral views revealed a difference of 1.6 degrees for femur lateral and 1.4 degrees for the tibia lateral. There was no significant (p > 0.05) influence of the parameters BMI and sex of the patients on these values. Our results showed that the implemented intraoperative navigation system is reliable. It does not differ on average from postoperative radiographs by more than 1.8 degrees. The findings of our study suggest that a correct postoperative alignment can be achieved in both high and low BMI participants if a precise range is maintained during the surgery.


Assuntos
Artroplastia do Joelho/métodos , Fêmur/diagnóstico por imagem , Prótese do Joelho , Cirurgia Assistida por Computador/métodos , Tíbia/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Pesos e Medidas Corporais , Feminino , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Postura , Radiografia , Amplitude de Movimento Articular , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tíbia/cirurgia , Suporte de Carga
19.
Oncotarget ; 8(58): 98623-98634, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228715

RESUMO

Most genome-wide association studies (GWAS) were analyzed using single marker tests in combination with stringent correction procedures for multiple testing. Thus, a substantial proportion of associated single nucleotide polymorphisms (SNPs) remained undetected and may account for missing heritability in complex traits. Model selection procedures present a powerful alternative to identify associated SNPs in high-dimensional settings. In this GWAS including 1060 colorectal cancer cases, 689 cases of advanced colorectal adenomas and 4367 controls we pursued a dual approach to investigate genome-wide associations with disease risk applying both, single marker analysis and model selection based on the modified Bayesian information criterion, mBIC2, implemented in the software package MOSGWA. For different case-control comparisons, we report models including between 1-14 candidate SNPs. A genome-wide significant association of rs17659990 (P=5.43×10-9, DOCK3, chromosome 3p21.2) with colorectal cancer risk was observed. Furthermore, 56 SNPs known to influence susceptibility to colorectal cancer and advanced adenoma were tested in a hypothesis-driven approach and several of them were found to be relevant in our Austrian cohort. After correction for multiple testing (α=8.9×10-4), the most significant associations were observed for SNPs rs10505477 (P=6.08×10-4) and rs6983267 (P=7.35×10-4) of CASC8, rs3802842 (P=8.98×10-5, COLCA1,2), and rs12953717 (P=4.64×10-4, SMAD7). All previously unreported SNPs demand replication in additional samples. Reanalysis of existing GWAS datasets using model selection as tool to detect SNPs associated with a complex trait may present a promising resource to identify further genetic risk variants not only for colorectal cancer.

20.
Sci Rep ; 7(1): 11298, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28900153

RESUMO

Left ventricular hypertrophy (LVH) ultimately leads to heart failure in conditions of increased cardiac pre- or afterload. The bone-derived phosphaturic and sodium-conserving hormone fibroblast growth factor-23 (FGF23) and its co-receptor Klotho have been implicated in the development of uremic LVH. Using transverse aortic constriction (TAC) in gene-targeted mouse models, we examine the role of Fgf23 and Klotho in cardiac hypertrophy and dysfunction induced by pressure overload. TAC profoundly increases serum intact Fgf23 due to increased cardiac and bony Fgf23 transcription and downregulation of Fgf23 cleavage. Aldosterone receptor blocker spironolactone normalizes serum intact Fgf23 levels after TAC by reducing bony Fgf23 transcription. Notably, genetic Fgf23 or Klotho deficiency does not influence TAC-induced hypertrophic remodelling, LV functional impairment, or LV fibrosis. Despite the profound, aldosterone-mediated increase in circulating intact Fgf23 after TAC, our data do not support an essential role of Fgf23 or Klotho in the pathophysiology of pressure overload-induced cardiac hypertrophy.


Assuntos
Cardiomegalia/etiologia , Cardiomegalia/fisiopatologia , Fatores de Crescimento de Fibroblastos/genética , Técnicas de Inativação de Genes , Glucuronidase/genética , Aldosterona/farmacologia , Animais , Biomarcadores , Pressão Sanguínea , Cardiomegalia/diagnóstico , Cardiomegalia/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Fibrose , Regulação da Expressão Gênica , Glucuronidase/metabolismo , Camundongos , Camundongos Knockout , Transdução de Sinais/efeitos dos fármacos , Espironolactona/farmacologia
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