scholarly journals Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT

2019 ◽  
Author(s):  
Zhimin Zhang ◽  
Ge Wang ◽  
Feng Jin ◽  
Jijun Zheng ◽  
He Xiao ◽  
...  
Keyword(s):  
Regression Model ◽  
Distant Metastasis ◽  
Clinical Remission ◽  
Cox Regression ◽  
Rank Test ◽  
Control Group ◽  
Cox Regression Model ◽  
Serum Mirnas ◽  
Significant Difference ◽  
Before And After

Abstract Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG) , who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. We used the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 9 down-regulated miRNAs, 1 up-regulated and 6 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After significantly down-regulated miRNAs from EG versus CG were removed, only 9 different miRNAs were significantly reduced. In the serum samples of 48 NPC patients, there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT. We calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=004）. Conclusions: For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs such as miRNA-29a, miRNA-125b and miRNA-26b etc, play an important role in predicting prognosis factors for PFS and OS, which will contribute to the strategic direction of future research.

scholarly journals Serum miRNAs, a potential prognosis marker of loco-regionally advanced nasopharyngeal carcinoma patients treated with CCRT

2019 ◽  
Author(s):  
Zhimin Zhang ◽  
jiangbiao Huang ◽  
Ge Wang ◽  
Feng Jin ◽  
Jijun Zheng ◽  
...  
Keyword(s):  
Regression Model ◽  
Distant Metastasis ◽  
Clinical Remission ◽  
Cox Regression ◽  
Rank Test ◽  
Control Group ◽  
Cox Regression Model ◽  
Serum Mirnas ◽  
Significant Difference ◽  
Before And After

Abstract Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=0.04). Conclusions : For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.

scholarly journals Detection of expression of microRNAs in serum of loco-regionally advanced nasopharyngeal carcinoma patients: A potential marker for prognosis prediction of nasopharyngeal carcinoma treated with concurrent chemoradiotherapy screening

2019 ◽  
Author(s):  
Zhimin Zhang ◽  
Ge Wang ◽  
Feng Jin ◽  
Jijun Zheng ◽  
He Xiao ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Regression Model ◽  
Risk Score ◽  
Distant Metastasis ◽  
Concurrent Chemoradiotherapy ◽  
Cox Regression ◽  
Cox Regression Model ◽  
Serum Mirna ◽  
Before And After

Abstract Background Serum miRNA signature has recently been found as potential disease fingerprints to predict survival. Therefore we investigated the role of serum miRNA in predicting prognosis in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT). Methods This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG), who were treated with CCRT within 5 years. The paired serum was collected before and after treatment and biomarkers were discovered by TaqMan Human MiRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients treated with CCRT. We used the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results Using fold change≥2.0 or ≤0.5 and p≤0.05 as a cutoff level, we identified 1 up-regulated and 9 down-regulated miRNAs, 1 up-regulated and 6 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After significantly down-regulated miRNA from EG versus CG before and after CCRT were removed, only 9 different miRNAs were significantly reduced. In an independent set of serum samples, the expression of miR-26b, miR-29a and miR-125b showed no significant difference in 48 NPC patients before CCRT. The expression of miR-143 and miR-29b showed no significantly difference between the two groups after CCRT. We calculated a risk score from the expression of miR-26b、miR-29a、miR-125b、miR-29b、miR-143 and then classified patients as with high or low risk. Compared to patients with low-risk score, high-risk patients had shorter PFS and OS. Cox regression model suggested that combining serum miR-29a and miR-125b before CCRT with miR-26b after CCRT was independent prognostic factors for PFS, whereas combining the former two is independent for OS. Conclusions Combined expression of serum miR-29a, miR-125b and miR-26b might provide prognostic value in loco-regionally advanced NPC patients treated with CCRT, especially for high-risk progression patients.

scholarly journals 813. The Reduction of the acquisition rate of carbapenem resistant Acinetobacter baumannii after room privatization in the intensive care unit

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S448-S449
Author(s):  
Jongtak Jung ◽  
Pyoeng Gyun Choe ◽  
Chang Kyung Kang ◽  
Kyung Ho Song ◽  
Wan Beom Park ◽  
...  
Keyword(s):  
Regression Model ◽  
Acinetobacter Baumannii ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Intervention Group ◽  
Feeding Tube ◽  
Control Group ◽  
Cox Regression Model ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Abstract Background Acinetobacter baumannii is one of the major pathogens of hospital-acquired infection recently and hospital outbreaks have been reported worldwide. On September 2017, New intensive care unit(ICU) with only single rooms, remodeling from old ICU with multibed bay rooms, was opened in an acute-care tertiary hospital in Seoul, Korea. We investigated the effect of room privatization in the ICU on the acquisition of carbapenem-resistant Acinetobacter baumannii(CRAB). Methods We retrospectively reviewed medical records of patients who admitted to the medical ICU in a tertiary care university-affiliated 1,800-bed hospital from 1 January 2015 to 1 January 2019. Patients admitted to the medical ICU before the remodeling of the ICU were designated as the control group, and those who admitted to the medical ICU after the remodeling were designated as the intervention group. Then we compared the acquisition rate of CRAB between the control and intervention groups. Patients colonized with CRAB or patients with CRAB identified in screening tests were excluded from the study population. The multivariable Cox regression model was performed using variables with p-values of less than 0.1 in the univariate analysis. Results A total of 1,105 cases admitted to the ICU during the study period were analyzed. CRAB was isolated from 110 cases in the control group(n=687), and 16 cases in the intervention group(n=418). In univariate analysis, room privatization, prior exposure to antibiotics (carbapenem, vancomycin, fluoroquinolone), mechanical ventilation, central venous catheter, tracheostomy, the presence of feeding tube(Levin tube or percutaneous gastrostomy) and the length of ICU stay were significant risk factors for the acquisition of CRAB (p< 0.05). In the multivariable Cox regression model, the presence of feeding tube(Hazard ratio(HR) 4.815, 95% Confidence interval(CI) 1.94-11.96, p=0.001) and room privatization(HR 0.024, 95% CI 0.127-0.396, p=0.000) were independent risk factors. Table 1. Univariate analysis of Carbapenem-resistant Acinetobacter baumannii Table 2. Multivariable Cox regression model of the acquisition of Carbapenem-resistant Acinetobacter baumannii Conclusion In the present study, room privatization of the ICU was correlated with the reduction of CRAB acquisition independently. Remodeling of the ICU to the single room would be an efficient strategy for preventing the spreading of multidrug-resistant organisms and hospital-acquired infection. Disclosures All Authors: No reported disclosures

scholarly journals 551. Remdesivir and Tocilizumab for the Treatment of Severe COVID-19 in a Community Hospital: A Retrospective Cohort Study

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S378-S379
Author(s):  
Guillermo Rodriguez-Nava ◽  
Goar Egoryan ◽  
Daniela Patricia Trelles-Garcia ◽  
Maria Adriana Yanez-Bello ◽  
Qishuo Zhang ◽  
...  
Keyword(s):  
Regression Model ◽  
Community Hospital ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Rank Test ◽  
Hospital Death ◽  
P Value ◽  
Survival Curves ◽  
Cox Regression Model ◽  
Kaplan Meier

Abstract Background Growing evidence supports the use of remdesivir and tocilizumab for the treatment of hospitalized patients with severe COVID-19. The purpose of this study was to evaluate the use of remdesivir and tocilizumab for the treatment of severe COVID-19 in a community hospital setting. Methods We used a de-identified dataset of hospitalized adults with severe COVID-19 according to the National Institutes of Health definition (SpO2 < 94% on room air, a PaO2/FiO2 < 300 mm Hg, respiratory frequency > 30/min, or lung infiltrates > 50%) admitted to our community hospital located in Evanston Illinois, between March 1, 2020, and March 1, 2021. We performed a Cox proportional hazards regression model to examine the relationship between the use of remdesivir and tocilizumab and inpatient mortality. To minimize confounders, we adjusted for age, qSOFA score, noninvasive positive-pressure ventilation, invasive mechanical ventilation, and steroids, forcing these variables into the model. We implemented a sensitivity analysis calculating the E-value (with the lower confidence limit) for the obtained point estimates to assess the potential effect of unmeasured confounding. Figure 1. Kaplan–Meier survival curves for in-hospital death among patients treated with and without steroids The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 2. Kaplan–Meier survival curves for in-hospital death among patients treated with and without remdesivir The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Results A total of 549 patients were included. The median age was 69 years (interquartile range, 59 – 80 years), 333 (59.6%) were male, 231 were White (41.3%), and 235 (42%) were admitted from long-term care facilities. 394 (70.5%) received steroids, 192 (34.3%) received remdesivir, and 49 (8.8%) received tocilizumab. By the cutoff date for data analysis, 389 (69.6%) patients survived, and 170 (30.4%) had died. The bivariable Cox regression models showed decreased hazard of in-hospital death associated with the administration of steroids (Figure 1), remdesivir (Figure 2), and tocilizumab (Figure 3). This association persisted in the multivariable Cox regression controlling for other predictors (Figure 4). The E value for the multivariable Cox regression point estimates and the lower confidence intervals are shown in Table 1. Figure 3. Kaplan–Meier survival curves for in-hospital death among patients treated with and without tocilizumab The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 4. Forest plot on effect estimates and confidence intervals for treatments The hazard ratios were derived from a multivariable Cox regression model adjusting for age as a continuous variable, qSOFA score, noninvasive positive-pressure ventilation, and invasive mechanical ventilation. Table 1. Sensitivity analysis of unmeasured confounding using E-values CI, confidence interval. Point estimate from multivariable Cox regression model. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully: i.e., a confounder not included in the multivariable Cox regression model associated with remdesivir or tocilizumab use and in-hospital death in patients with severe COVID-19 by a hazard ratio of 1.64-fold or 1.54-fold each, respectively, could explain away the lower confidence limit, but weaker confounding could not. Conclusion For patients with severe COVID-19 admitted to our community hospital, the use of steroids, remdesivir, and tocilizumab were significantly associated with a slower progression to in-hospital death while controlling for other predictors included in the models. Disclosures All Authors: No reported disclosures

scholarly journals Μελέτη της GSK-3β σε πρωτεϊνικό και μοριακό επίπεδο σε οικογενή και σποραδικά καρκινώματα μαστού

2018 ◽  
Author(s):  
Ιωάννης Βαμβακάρης
Keyword(s):  
Regression Model ◽  
Cox Regression ◽  
Rank Test ◽  
Ki 67 ◽  
Cox Regression Model ◽  
Activating Mutations ◽  
Log Rank Test ◽  
Her 2 ◽  
Gsk 3Β

ΕΙΣΑΓΩΓΗ Ο καρκίνος του μαστού είναι η κυριότερη αιτία θανάτου σχετιζόμενου με καρκίνο στις γυναίκες σε παγκόσμιο επίπεδο. Παρότι παρατηρείται αύξηση της συχνότητας πρωτοεμφανιζόμενης νόσου, οι ρυθμοί θανάτου μειώνονται. Το γεγονός αυτό οφείλεται, κυρίως στην ενημέρωση ,στα μοντέλα πρόληψης, στην εκτενή χρήση της μαστογραφίας και στην πρόοδο των εφαρμοζόμενων θεραπευτικών μέσων . Το δεδομένο αυτό επιβάλλει την διεύρυνση των ερευνητικών μας οριζόντων προς πεδία που υπόσχονται αξιόπιστα αποτελέσματα στην διάγνωση, πρόγνωση και θεραπεία. ΣΚΟΠΟΣ Ο σκοπός της παρούσης μελέτης είναι: 1) Η διερεύνηση του προτύπου έκφρασης της πρωτεϊνικής κινάσης GSK-3β σε διηθητικά καρκινώματα μαστού (σποραδικά και οικογενή), 2) Η ύπαρξη τυχόν μεταλλάξεων στο γονίδιο της GSK-3β που εδρεύει στο χρωμόσωμα 3q13.3. Τα αποτελέσματα που θα προκύψουν θα συσχετιστούν με: α) κλασσικές κλινικοπαθολογοανατομικές παραμέτρους (ηλικία, εμμηνοπαυσιακή κατάσταση, μέγεθος όγκου, ιστολογικός τύπος, ιστολογικός και πυρηνικός βαθμός κακοήθειας, στάδιο της νόσου και ορμονικούς υποδοχείς), β) ολική και ελευθέρα νόσου επιβίωση των ασθενών, γ) βιολογικούς δείκτες (ER, PR ,β-κατενίνη, AKT, m-TOR). Τελικός σκοπός είναι να βρεθούν συσχετισμοί της έκφρασης της GSK-3β σε πρωτεϊνικό και μοριακό επίπεδο σε σποραδικά ή και οικογενή διηθητικά καρκινώματα μαστού. ΥΛΙΚΟ ΚΑΙ ΜΕΘΟΔΟΛΟΓΙΑΑ) Υλικό-μέθοδοςΤο υλικό αποτελείται από: α) 154 σποραδικά διηθητικά καρκινώματα μαστού, β) 112 οικογενή διηθητικά καρκινώματα μαστού και γ) 20 δείγματα μαζικού ιστού, αρνητικά για κακοήθεια που θα αποτελέσουν την ομάδα ελέγχου (control). Ο προσδιορισμός της έκφρασης της GSK-3β στα διηθητικά καρκινώματα μαστού θα γίνει σε τομές παραφίνης με την εφαρμογή ανοσοϊστοχημικών μεθόδων. Η ανίχνευση τυχόν μεταλλάξεων του γονιδίου της GSK-3β θα γίνει με απομόνωση από τομές παραφίνης και χρήση της αλυσιδωτής αντίδρασης πολυμεράσης (PCR).Β) Έκφραση της πρωτεϊνικής κινάσης GSK-3β με ανοσοϊστοχημεία. Εφαρμόστηκε ανοσοϊστοχημική μέθοδος τριών βημάτων (αβιδίνης-βιοτίνης-υπεροξειδάσης) για τον προσδιορισμό της έκφρασης της πρωτεϊνικής κινάσης GSK-3β σε τομές παραφίνης. Η αντιγονική αποκάλυψη έγινε με θέρμανση των τομών με διάλυμα EDTA pH 8.0 (Trilogy), σε φούρνο μικροκυμάτων για 15 λεπτά. Το αντίσωμα που χρησιμοποιήθηκε ήταν το rabbit polyclonal GSK-3β (H-76), σε αραίωση 1:70.Γ) Ανίχνευση μεταλλάξεων στα εξώνια 5 και 6 του γονιδίου gsk-3βΓια την ανίχνευση της ύπαρξης τυχόν μεταλλάξεων στα εξώνια 5 και 6 του γονιδίου της GSK-3β εφαρμόστηκε, μετά από απομόνωση του DNA από ιστικές τομές παραφίνης (QIAamp DNA Mini Kit), η μέθοδος της αλυσιδωτής αντίδρασης πολυμεράσης (PCR) με τους αντίστοιχους εκκινητές (primers) και ακολούθως ηλεκτροφόρηση σε gel αγαρόζης. Δεδομένης της απουσίας βιβλιογραφικών αναφορών σχετικά με μεταλλάξεις στα συγκεκριμένα εξώνια του γονιδίου, σε πρώτη φάση έγινε αλληλούχιση (sequencing) των προϊόντων της PCR, σε τυχαία περιστατικά, για τον καθορισμό των επιμέρους φυσικών παραγόντων (θερμοκρασία, χρόνοι και αριθμοί κύκλων αντίδρασης), με σκοπό τη βελτιστοποίηση των συνθηκών της μεθόδου και την ασφαλή προτυποποίησή της. Μόλις τα αποτελέσματα της τεχνικής διαδικασίας κρίθηκαν αξιόπιστα και επαναλαμβανόμενα ακολούθησε η αλληλούχιση (sequencing) των προϊόντων της PCR, στα περιστατικά της παρούσης μελέτης.Δ) Στατιστική μεθοδολογίαΓια τη στατιστική επεξεργασία των αποτελεσμάτων χρησιμοποιήθηκε η μονοπαραγοντική ανάλυση χ2 για τη συσχέτιση με τους βιολογικούς δείκτες, καθώς και μονοπαραγοντική (log rank test) και πολυπαραγοντική (Cox regression model) για τη συσχέτιση με την επιβίωση των ασθενών. Τα ανοσοϊστοχημικά δεδομένα που χρησιμοποιήθηκαν στη στατιστική επεξεργασία προκύπτουν από τα έως τώρα ανευρεθέντα στοιχεία της μελέτης μας, τα δε μοριακά δεδομένα όσο αναφορά τις μεταλλάξεις στα εξώνια 5 και 6 του γονιδίου της GSK-3β προέκυψαν και αυτά από τα στοιχεία της μελέτης μας. Τα στατιστικά που χρησιμοποιήσαμε στην διαδικασία βελτιστοποίησης της μεθόδου δεν αναφέρονται. ΑΠΟΤΕΛΕΣΜΑΤΑΗ GSK-3β εντοπίστηκε στο κυτταρόπλασμα των καρκινικών κυττάρων των διηθητικών καρκινωμάτων μαστού σε 133 (57.1%) περιπτώσεις, καθώς και στις στρωματικές ινοβλάστες σε 67 (28.7%) περιπτώσεις, από το σύνολο των 266 περιπτώσεων που μελετήθηκαν. Ταυτόχρονη καρκινική και στρωματική ανοσοεντόπιση της GSK-3β παρατηρήθηκε σε 63 (27%) περιπτώσεις Η κυτταροπλασματική και στρωματική έκφραση της GSK-3β στα καρκινικά κύτταρα δεν συσχετίσθηκε με καμία από τις κλασικές κλινικοπαθολογοανατομικές παραμέτρους του καρκινώματος μαστού(μέγεθος νεοπλάσματος,στάδιο νόσου,εμμηνοπαυσιακή κατάστασηιστολογικός τύπος,πυρηνικός βαθμός κακοήθειας,διήθηση επιχώριων λεμφαδένων)ούτε με το οικογενειακό ιστορικό.Η κυτταροπλασματική εντόπιση της πρωτεΐνης GSK-3β συσχετίστηκε παράλληλα με την ανοσοϊστοχημική έκφραση των πρωτεϊνών HER-2 και Akt (p=0.045 και p=0.039, αντίστοιχα) και ανάστροφα με την έκφραση της πρωτεΐνης PTEN (p=0.011) Η στρωματική έκφραση της GSK-3β συσχετίστηκε παράλληλα με την έκφραση της πρωτεΐνης κασπάση-3 (p=0.020) και ανάστροφα με την έκφραση των οιστρογονικών υποδοχέων (ER) (p=0.035) και την ανοσοϊστοχημική έκφραση των πρωτεϊνών Ki-67 και pAkt (p=0.015 και p=0.046, αντίστοιχα) Η κυτταροπλασματική έκφραση καθώς και η ανοσοεντόπιση στις στρωματικές ινοβλάστες της πρωτεΐνης GSK-3β δεν βρέθηκε να ασκεί κάποια επίδραση στην ολική και ελευθέρα νόσου επιβίωση στο σύνολο των ασθενών και στις υποομάδες των σποραδικών και οικογενών καρκινωμάτων, τόσο στη μονοπαραγοντική όσο και στην πολυπαραγοντική στατιστική ανάλυση. Ωστόσο, η κυτταροπλασματική έκφραση της πρωτεΐνης βρέθηκε να ασκεί μη ευνοϊκή επίδραση στην ελευθέρα νόσου επιβίωση των ασθενών με HER-2 – αρνητικά καρκινώματα μαστού (p=0.021), στη μονοπαραγοντική στατιστική ανάλυσηΓια την ανεύρεση τυχόν ενεργοποιητικών μεταλλάξεων (activating mutations) στα εξώνια 5 και 6 του γονιδίου της GSK-3β κινάσης, επελέγησαν 40 περιστατικά στα οποία παρατηρήθηκε υπερέκφραση της πρωτεΐνης καθώς και 10 ως αρνητικοί μάρτυρες. Ωστόσο, παρά τις δοκιμές για τον προσδιορισμό των βέλτιστων συνθηκών, δεν παρατηρήθηκαν τέτοιου είδους μεταλλάξεις. Το γεγονός αυτό μπορεί να υποδηλώνει ότι η υπερέκφραση της πρωτεΐνης GSK-3β στον καρκίνο του μαστού πιθανά οφείλεται σε μετα-μεταφραστικές τροποποιήσεις ή σε καταστολή των φυσικών της αναστολέων. ΣΥΜΠΕΡΑΣΜΑΤΑ Ο ρόλος της πρωτεινης GSK-3β στην εξέλιξη του καρκίνου ακόμα δεν έχει τυποποιηθεί πλήρως καθώς υπάρχουν μελέτες με αντικρουόμενα ή και παράδοξα αποτελέσματα. Υπάρχουν μελέτες που υποστηρίζουν την ογκοκατασταλτική δράση της πρωτεΐνης σε κάποια καρκινώματα και άλλες που αποδίδουν στην πρωτεΐνη ογκογόνο .Η απουσία μεταλλάξεων ,εύρημα παρατηρούμενο σε όλες τις νεοπλασματικές και μη νόσους ,δεν έχει επιτρέψει έως τώρα την στοχευμένη θεραπευτική προσέγγιση.

scholarly journals Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Yong Cui ◽  
Wei Zeng ◽  
Haihui Jiang ◽  
Xiaohui Ren ◽  
Song Lin ◽  
...  
Keyword(s):  
Regression Model ◽  
Brain Region ◽  
Cox Regression ◽  
Metabolic Parameters ◽  
Resonance Spectroscopy ◽  
Normal Brain ◽  
Peritumoral Edema ◽  
Cox Regression Model ◽  
Significant Difference ◽  
Contralateral Normal Brain

Objective: To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS).Methods: The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis and Cox regression model were used to identify parameters correlated with progression-free survival (PFS) and overall survival (OS).Results: Compared with the contralateral normal brain region, postoperative PEZ showed a lower ratio of NAA/Cr (1.20 ± 0.42 vs. 1.81 ± 0.48, P < 0.001), and higher ratios of Cho/Cr and Cho/NAA (1.36 ± 0.44 vs. 1.02 ± 0.27, P < 0.001 and 1.32 ± 0.59 vs. 0.57 ± 0.14, P < 0.001). Both the ratios of Cho/NAA and NAA/Cr were identified as prognostic factors in univariate analysis (P < 0.05), while only Cho/NAA ≥ 1.31 was further confirmed as an independent risk factor for early recurrence in the Cox regression model (P < 0.01). According to the factors of MGMT promoter unmethylation, without radiotherapy and Cho/NAA ≥ 1.31, a prognostic scoring scale for GBM was established, which could divide patients into low-risk, moderate-risk, and high-risk groups. There was a significant difference of survival rate between the three groups (P < 0.001).Conclusions: Higher Cho/NAA ratio in the postoperative PEZ of GBM predicts earlier recurrence and is associated with poor prognosis. The prognostic scoring scale based on clinical, molecular and metabolic parameters of patients with GBM can help doctors to make more precise prediction of survival time and to adjust therapeutic regimens.

scholarly journals The Effect of Brainstorming Implementation on Students’ Engagement in Learning about Probability in Math Classes in Grade XI IPA at SMA ABC Cikarang

2017 ◽  
Vol 12 (1) ◽  
pp. 20
Author(s):  
Elsar Agung Triansa ◽  
Juniriang Zendrato ◽  
Oce Datu Appulembang
Keyword(s):  
Sampling Technique ◽  
Rank Test ◽  
Control Group ◽  
Group Data ◽  
Signed Rank ◽  
Significant Difference ◽  
Before And After ◽  
Quasi Experimental ◽  
Signed Rank Test ◽  
Equivalent Control

<p>This research aims to determine the effects of brainstorming on students’ engagement in learning about probability. The method used in this research is the quasi-experimental with a non-equivalent control group. The sampling technique is in the form of a census. The data was collected through a questionnaire and analyzed by using non-parametric tests -- the Mann-Whitney U-test and the Wilcoxon Signed-Rank test with alpha level of 0.05. The results show that: 1) there was no significant difference on students’ engagement before and after the experiment in the group that was taught without brainstorming; 2) there was significant difference on students’ engagement before and after the experiment in the group taught with brainstorming; and 3) there was no significant difference on students’ engagement between the group that was taught with brainstorming and the group that was taught without brainstorming. The result of this research indicates that implementing brainstorming produces a positive effect on students’ engagement in learning about probability in math classes in grade XI IPA at SMA ABC Cikarang.</p><p><em><span class="showMoreLessContentElement" style="display: inline;">BAHASA INDONESIA ABSTRAK</span>: Penelitian ini bertujuan untuk menemukan pengaruh penerapan brainstorming terhadap keterlibatan siswa dalam mempelajari topik peluang.Metode yang digunakan dalam penelitian ini adalah quasi-eksperimen dengan desain non-equivalent control group. Data dikumpulkan melalui kuisioner dan dianalisis dengan uji non-parametrik, yaitu uji Mann-Whitney U dan uji Wilcoxon Signed-Rank dengan taraf signifikansi 0.05.Hasil penelitian menunjukkan bahwa: 1) tidak ada perbedaan yang signifikan dalam keterlibatan siswa antara sebelum dan sesudah perlakuan di grup yang diajar tanpa brainstorming (hasil uji Wilcoxon Signed-Rank: ); 2) ada perbedaan yang signifikan pada keterlibatan siswa antara sebelum dan sesudah perlakuan di grup yang diajar dengan brainstorming (hasil uji Wilcoxon Signed-Rank: ); dan 3) tidak ada perbedaan yang signifikan pada keterlibatan siswa antara grup yang diajar dengan brainstorming dan tanpa brainstorming (hasil uji Mann-Whitney U: ). Hasil dari penelitian ini mengindikasikan bahwa penerapan brainstorming memberikan pengaruh yang positif terhadap keterlibatan siswa dalam mempelajari peluang di pelajaran matematika kelas XI IPA SMA ABC Cikarang.</em></p>

scholarly journals The Research and Analysis of Bring Perigastric Tumor Deposits into The Staging of Primary Gastric Cancer

2020 ◽  
Author(s):  
Xinxin Wang ◽  
Zhaoyang Wang ◽  
Tianyu Xie ◽  
Shuo Li ◽  
Di Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Model ◽  
Cox Regression ◽  
Survival Curve ◽  
Statistical Significance ◽  
Tnm Staging ◽  
Gastric Body ◽  
Rank Test ◽  
Control Group ◽  
Primary Gastric Cancer

Abstract Background: The current significance of perigastric tumor deposits (TDs) in gastric cancer (GC) for indicating prognosis remains unclear. The aim of this study was to assess the prognostic value of perigastric TDs and a new TNM staging involving TDs for GC.Methods: The pathological data of 6672 patients with GC who underwent gastrectomy or operation of gastric cancer with other diseases between January 1, 2012 and December 31, 2017 at Chinese PLA General Hospital were analyzed retrospectively. The patients were divided into tumor deposits positive (TD+) group and tumor deposits negative (TD-) group. The differences between TD+ and TD- were analyzed by binary Logistic regression model. To draw survival curves, we used Kaplan-Meier methods. Multivariate Cox regression model and Log-rank test was used to analyze the data.Results: Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC of which 237 were males (69.91%) and 102 females (30.09%) (2.32:1). The median age was 59 years (ranging from 27 to 78 years). No significant differences were detected between the two groups. Univariate and multivariate survival analysis both indicated that GC patients with positive TDs had poorer prognosis than those with negative TDs (p<0.05). The 1-, 3-and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and were significantly poorer than those of the staged matched control group. There was statistical significance between the location of TDs and patient survival in patients with gastric cancer (p＜0.05). A new TNM staging was formulated according to the TDs location. When TDs appear on the gastric body, the original T1, T2, T3 stages change to T4a, and T4a, T4b change to T4b; when TDs appear in the lesser curvature, the previous N0, N1, N2, N3 stage change to N3; when the TDs located in the greater curvature or the distant tissue, the patient should be categorized as M1. After using the new stage, the survival curve of patients with TDs was closer to that of patients without TDs in each pTNM staging.Conclusion: 1. Tumor deposits is a bad prognostic factor in patients with primary gastric cancer. 2. The location of tumor deposits is associated with the prognosis of patients with primary gastric cancer. 3. The new stage is more suitable for patients with tumor deposits of gastric cancer.

scholarly journals Impact of Non-synchronous Diagnostic Ureteroscopy on Intravesical Recurrence in Patients Underwent Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Propensity-Score Matched Analysis

2019 ◽  
Author(s):  
Huamao Ye ◽  
Xiang Feng ◽  
Yang Wang ◽  
Rui Chen ◽  
Meimian Hua ◽  
...  
Keyword(s):  
Propensity Score ◽  
Regression Model ◽  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Control Group ◽  
Radical Nephroureterectomy ◽  
Cox Regression Model ◽  
Upper Tract ◽  
The Impact

Abstract Background: The effect of diagnostic ureteroscopy (DURS) on intravesical recurrence (IVR) after radical nephroureterectomy (RNU) were controversial. To investigate the impact of DURS, we carried out this single-center retrospective study by applying propensity-score matching (PSM) and Cox regression model. Patients and Methods: The data of 160 patients with pTa-pT3 upper tract urothelial carcinoma (UTUC) were analyzed. Eighty-six patients underwent DURS (DURS group) and 74 patients without DURS (control group). The DURS group was further sub-grouped into synchronous DURS group (DURS followed by immediate RNU, n=45) and non-synchronous DURS group (DURS followed by delayed RNU, n=41). Baseline confounders were corrected by PSM. The impact of DURS on IVR was assessed by Kaplan-Meier analysis in PSM cohort and by Cox regression model in the full data set. Results: The median follow-up time was 40.4 months. No difference of the 3-year IVRFS between DURS group and control group (72.6% vs. 65.3%, p=0.263). In subgroup analysis, the 3-year IVR-free survival of non-synchronous DURS group (51.4%) was significantly lower than that of synchronous DURS (78.3%) or control group (72.6%) (p=0.027). Further Cox regression analysis showed that non-synchronous DURS (HR 1.481, 95% CI 1.031-2.127, p=0.034) was independent risk factors for postoperative IVR. Conclusions: Non-synchronous DURS was not recommended for the diagnosis and preoperative evaluation of UTUC, because it could raise the risk of IVR after RNU. For UTUC patients in need of DURS, synchronous DURS could be a safer choice than the non-synchronous DURS in terms of lowering the IVR risk.

scholarly journals An Investigation Into the Beneficial Effects of High-Dose Interferon beta 1-a, Compared to Low-Dose Interferon Beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19

2021 ◽  
Author(s):  
Ilad Alavi Darazam ◽  
Firouze Hatami ◽  
Mohammad Mahdi Rabiei ◽  
Mohamad Amin Pourhoseingholi ◽  
Minoosh Shabani ◽  
...  
Keyword(s):  
Regression Model ◽  
Low Dose ◽  
Interferon Beta ◽  
Cox Regression ◽  
Intervention Group ◽  
Control Group ◽  
P Value ◽  
High Dose ◽  
Cox Regression Model ◽  
Subcutaneous Injections

Abstract Introduction: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high dose IFN-β 1a compared to low dose IFN-β 1a (the base therapeutic regimen) in moderate to severe COVID-19 cases.Methods: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) and the control group was treated with low dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally, in all two groups). Result:A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low dose of IFN-β1a was shorter than that for cases treated with high dose of IFN-β1a (6 vs10 days; P=0.018). Hazard Ratio for TTCI in the Cox regression model was 1.56 (95% CI: 1.05-2.30, P-value=0.026). Due to differences between some baseline clinical factors between intervention and control group, we; therefore, performed an adjusted analysis by including spo2, D-dimer and CRP in Cox regression model. The model failed to reach a significant difference between two groups. The adjusted HR was 1.37 (95% CI: 0.88-2.12, P-value=0.16). No difference was observed in terms of mortality between two groups. ConclusionThe use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it has not any significant effect in mortality reduction compared with treating with low-dose IFN-β 1a.Trial registration: The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04521400.

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