Colorectal cancer (CRC) is the third most common cancer worldwide. The high mortality from CRC is mainly related to metastasis affecting distant organs and their function. Dissemination of tumor ...cells from the primary tumor and hematogeneous spread are considered crucial in the formation of tumor metastases. The analysis of circulating tumor cells (CTCs) and CTC clusters in the blood can be used for the early detection of invasive cancer. Moreover, CTCs have a prognostic significance in the monitoring of a malignant disease or the response to chemotherapy. This work presents an overview of the research conducted on CTCs with the aim of finding suitable detection systems and assessing the possibility of clinical applications in patients with CRC.
Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and ...miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.
Severe alcoholic hepatitis (AH) is a distinct entity in the spectrum of alcohol-related liver disease, with limited treatment options and high mortality. Supportive medical care with corticosteroids ...in selected patients is the only currently available treatment option, often with poor outcomes. Based on the insights into the pathogenetic mechanisms of AH, which are mostly obtained from animal studies, several new treatment options are being explored. Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target. Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor (G-CSF) on liver regeneration and immunomodulation in animal models, several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH. Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH, these effects were not confirmed by a recently published multicenter randomized trial, suggesting that other options should rather be pursued. Stem cell transplantation represents another option for improving liver regeneration, but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing, with established lack of efficacy in patients with compensated cirrhosis. In this review, we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration. The lack of high-quality studies and evidence is a major obstacle in further treatment development. New insights into the pathogenesis of not only liver injury, but also liver regeneration processes are mandatory for the development of new treatment options. A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing, and data obtained from animal studies are essential for future research.
Drug-specific therapeutic approaches for colorectal cancer (CRC) have contributed to significant improvements in patient health. Nevertheless, there is still a great need to improve the ...personalization of treatments based on genetic and epigenetic tumor profiles to maximize the quality and efficacy while limiting cytotoxicity. Currently, CEA and CA 19-9 are the only validated blood biomarkers in clinical practice. For this reason, laboratories are trying to identify new specific prognostics and, more importantly, predictive biomarkers for CRC patient profiling. Thus, the unique landscape of personalized biomarker data should have a clinical impact on CRC treatment strategies and molecular genetic screening tests should become the standard method for diagnosing CRC. This review concentrates on recent molecular testing in CRC and discusses the potential modifications in CRC assay methodology with the upcoming clinical application of novel genomic approaches. While mechanisms for analyzing circulating tumor DNA have been proven too inaccurate, detecting and analyzing circulating tumor cells and protein analysis of exosomes represent more promising options. Blood liquid biopsy offers good prospects for the future if the results align with pathologists' tissue analyses. Overall, early detection, accurate diagnosis and treatment monitoring for CRC with specific markers and targeted molecular testing may benefit many patients.
Objective: To compare the performance of the Glasgow Blatchford score (GBS), pre-endoscopic Rockall score (PRS) and AIMS65 score in predicting specific clinical endpoints following variceal upper ...gastrointestinal hemorrhage (UGIH).
Material and methods: Between January 2008 and December 2013, we retrospectively analyzed 225 consecutive hospitalized patients managed for endoscopically confirmed UGIH.
Results: A total of 225 patients (mean age 61.3 years), mostly diagnosed with alcoholic cirrhosis (195/86.7%), presented with variceal UGIH during the study period. Rebleeding occurred in 22 (9.8%) patients and 30-day mortality was 39 (17.3%). Initial hemostasis was achieved with N-butyl cyanoacrylate (151/79.1%) and endoscopic variceal ligation (40/20.9%), while secondary rebleeding prophylaxis in 110 (48.9%) patients was accomplished using endoscopic variceal ligation (92%). The majority of patients died from the underlying disease, while 12 (30.8%) died from bleeding. Median hospital stay was 6 (1-35) days. There was no statistically significant difference among AIMS65, GBS and PRS in predicting mortality (AUROC 0.70 vs. 0.64 vs. 0.66) or rebleeding rates (AUROC 0.74 vs. 0.60 vs. 0.67). The GBS was superior in predicting the need for blood transfusion compared to AIMS65 score (AUROC 0.75 vs. 0.61, p = 0.01) and PRS (AUROC 0.75 vs. 0.58, p = 0.009).
Conclusions: The AIMS65, GBS and PRS scores are comparable but not useful for predicting outcome in patients with variceal UGIH because of poor discriminative ability. The GBS is superior in predicting the need for transfusion compared to AIMS65 score and PRS.
In the pharmacokinetic analysis of ethanol after oral administration, only single- or two-compartment models are used, but their precision in estimating pharmacokinetic parameters might be ...insufficient. In a recent study, pharmacokinetic analysis using a modified Norberg three-compartment model was performed after oral administration of differently sweetened alcoholic solutions and compared to pharmacokinetic analysis using the classic Widmark model. On three occasions, eight male volunteers consumed differently sweetened alcoholic solutions: non-sweetened, sweetened with sucrose, and sweetened with steviol glycoside. Blood ethanol concentration was determined from samples obtained at t = 15, 30, 60, 90, 120, 180 min after consumption. Pharmacokinetic analysis was performed model independently, using the classic Widmarks model and using the modified Norberg model. Results showed that estimated pharmacokinetic parameters depend on the type of model used. The classic Widmark model in particular overestimated the fraction of absorbed ethanol from the gastrointestinal system to systemic circulation. Furthermore, the type of sweetener also affected pharmacokinetic parameters, although the difference was not statistically significant. In conclusion, the novel pharmacokinetic model, while being more physiological, fits experimental data better and hence is more suitable for modelling real-life alcohol consumption. In addition, the effect of natural non-caloric sweetener steviol glycoside on ethanol pharmacokinetics, analysed for the first time in the current research, might be different when compared to the common-used sweetener sucrose.
AIM To compare the Glasgow-Blatchford score(GBS), Rockall score(RS) and Baylor bleeding score(BBS) in predicting clinical outcomes and need for interventions in patients with bleeding peptic ulcers. ...METHODS Between January 2008 and December 2013, 1012consecutive patients admitted with peptic ulcer bleeding(PUB) were prospectively followed. The pre-endoscopic RS, BBS and GBS, as well as the post-endoscopic diagnostic scores(RS and BBS) were calculated for all patients according to their urgent upper endoscopy findings. Area under the receiver-operating characteristics(AUROC) curves were calculated for the prediction of lethal outcome, rebleeding, needs for blood transfusion and/or surgical intervention, and the optimal cutoff values were evaluated.RESULTS PUB accounted for 41.9% of all upper gastrointestinal tract bleeding, 5.2% patients died and 5.4% patients underwent surgery. By comparing the AUROC curves of the aforementioned pre-endoscopic scores, the RS best predicted lethal outcome(AUROC 0.82 vs 0.67 vs0.63, respectively), but the GBS best predicted need for hospital-based intervention or 30-d mortality(AUROC0.84 vs 0.57 vs 0.64), rebleeding(AUROC 0.75 vs 0.61 vs 0.53), need for blood transfusion(AUROC 0.83 vs0.63 vs 0.58) and surgical intervention(0.82 vs 0.63 vs 0.52) The post-endoscopic RS was also better than the post-endoscopic BBS in predicting lethal outcome(AUROC 0.82 vs 0.69, respectively).CONCLUSION The RS is the best predictor of mortality and the GBS is the best predictor of rebleeding, need for blood transfusion and/or surgical intervention in patients with PUB. There is no one ’perfect score’ and we suggest that these two tests be used concomitantly.
Antibiotic resistance is one of the biggest threats to global health today. The aim of this study was to analyze antibiotic prescribing patterns and quality of prescribing in Croatian dental ...practices over a 5-year period.
This is a retrospective observational study based on the analysis of the electronic prescriptions (medicines in ATC groups J01 and P01) from dental practices in Croatia prescribed from 1 January 2015 to 31 December 2019. Prescriptions were retrieved from the Croatian Health Insurance Fund (HZZO). The analyses included the number of prescriptions, type and quantity of prescribed drugs, indication, and the patient's and prescriber's characteristics.
The consumption increased from 1.98 DID in 2015, to 2.10 DID in 2019. The most prescribed antibiotic was Amoxicillin with clavulanic acid followed by Amoxicillin, Clindamycin, Metronidazole and Cefalexin. The analyses showed that 29.79% of antibiotics were not prescribed in accordance with the contemporary guidelines for the proper use of antibiotics. Additionally, 22% of antibiotics were prescribed in inconclusive indications.
The research showed an increase in antibiotic consumption over five years along with unnecessary prescribing of antibiotics in cases with no indications for its use. The development of national guidelines for antibiotic use is necessary.
Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by signs of intestinal obstruction lasting for 6 months or more, in the absence of a definitive cause of obstruction. We ...report a case of CIPO in a 49-year-old female patient with a 6-month history of ongoing irregular bowel movements, manifested as constipation and diarrhea accompanied by abdominal pain and bloated feeling. Contrast-enhanced abdominal computed tomography and magnetic resonance enterography revealed focal thickening of a segment of the lienal flexure and intermittent areas of wider and narrower caliber along the sigmoid colon. No signs of a definitive cause of obstruction were found, but evidence for dolichosigma was revealed, which was later confirmed with colonoscopy. Due to persisting symptoms, the patient agreed to elective resection of the sigmoid colon. Following the procedure, symptoms regressed with a significant improvement in the quality of life. The patient has been regularly monitored in an outpatient setting and reports absence of the symptoms since the procedure. Pathophysiology of the resected section revealed more prominent lymphatic tissue, follicular arrangement, and reactively altered germinal centers, which can suggest CIPO.
Dental health care workers, particularly dental medicine students (DMS), are at an increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The aim of our study was to assess ...the level of knowledge on HBV and HCV, estimate needlestick injury (NSI) prevalence and reporting practice in DMS at the University of Zagreb, and analyze how enrolment in obligatory and supplemental courses affects knowledge and NSI reporting practice. The knowledge was assessed by our questionnaires based on the Centers for Disease Control general handouts. Additional information was collected to examine the prevalence and reporting practice of NSI. Data were analyzed by descriptive statistical analysis, independent-samples t-test, proportion analyses, and combined factor analyses of categorical and quantitative variables in SPSS and R. In total, 206 students participated in the survey. The overall level of HBV- and HCV-related knowledge was poor, with the mean scores of 61.90% and 51.35%, respectively. Moreover, students enrolled in the first year demonstrated significantly lower levels of knowledge in comparison with their older peers. Of all participants, 18.2% had sustained a NSI and the majority of them (78.95%) had never reported the injury. In conclusion, DMS have low levels of knowledge on important occupational pathogens and poor NSI reporting practice. Moreover, formal education in the current form has failed to significantly improve student competence and theoretical knowledge translates poorly into more conscientious injury reporting practice. We should look for a better way to increase student awareness and level of knowledge on this topic. Key words: Hepatitis B; Hepatitis C; Dental education; Needlestick injury; Occupational pathogens; Occupational health
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