Mutational profiles and clinical outcomes in metastatic colorectal carcinoma patients with different metastases sites.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16020-e16020
Author(s):  
Xi Zhang ◽  
Zhang Jing ◽  
Yingmei Li ◽  
Shifu Chen

e16020 Background: To compare the difference of genomic and survival of first metastases site between first metastases site of metastatic colorectal cancer (mCRC) in liver and other sites (bone, brain, lung, and so on). Methods: Genomic mutations and clinic data of 113,4 CRCs (consisting of 533 metastases) were collected from TCGA database. According to first site(s) of metastases, patients were categorized into group 1 (liver as first metastases site, n = 405) and group 2 (other organs as first metastases site, n = 128). OS curves were estimated with Kaplan-Meier method, p values were calculated by fisher exact test. Results: Mutation frequency in GNAS (2.34%), KRAS (37.78%), BRAF (16.41%) and proportion of MSI-high (8.5%) was significantly higher in group2. Compared with group2, group1 showed significantly higher mutation rate of APC (78.52%) and TP53 (77.28%). We assessed overall survival in the two groups. OS was significantly better for patients in group1 than in group2 (HR 0.57, 95% CI 0.41-0.79, p = 0.00075). Conclusions: According to the results of this study, mCRC patients showed different mutational signatures with respect to the site of first metastases, and presented higher OS rate in liver metastases group. Our findings provided new knowledge to understand the biological progress of different metastases and develop new prognostic markers for metastatic colorectal cancer.

2004 ◽  
Vol 16 (2) ◽  
pp. 208
Author(s):  
C. Cuello ◽  
F. Berthelot ◽  
F. Martinat-Botté ◽  
P. Guillouet ◽  
V. Furstoss ◽  
...  

The present study was designed to determine the effect of pooling embryos from two donors on the reproductive success of transfer of vitrified/warmed porcine blastocysts. Superovulated Large White hyperprolific gilts (n=24) were used as embryo donors. Gilts were artificially inseminated 12 and 24h after initial detection of estrus using fresh semen, and slaughtered on Days 5.5 to 6 of the estrous cycle (Day 0=Onset of estrus). Embryos were recovered by flushing the uterine horns, and unhatched blastocysts were selected. Vitrification and warming were performed as reported previously (Berthelot et al., 2000 Cryobiology 41, 116–124). Embryo transfers were conducted in asynchronous (−24h) Meishan gilts (n=20). Twenty vitrified/warmed blastocysts were surgically transferred into one uterine horn. Ten recipients received embryos from one donor (group 1) and the other ten transfers were performed with mixed embryos from two donors (group 2). Pregnancy was assessed ultrasonographically at Day 25 after estrus and recipients were slaughtered five days later. The pregnancy rate from the different groups was compared using Fisher exact test. The GLM procedure of SAS was used to determine the effect of the origin of embryos (one or two donors) on the number of developed fetuses and viable fetuses at Day 30 of pregnancy. The ovulation rate was 32.5±11.8 (mean±SD). The total number of embryos collected was 634, of which 57 (9.0%), 36 (5.7%), 513 (80.9%) and 28 (4.4%), were unfertilized oocytes and degenerated embryos, morulae, unhatched blastocysts and hatched blastocysts, respectively. The ratio of collected embryos to the number of corpora lutea was 81.3%. The pregnancy rate for group 1 (70%) was not different (P>0.05) than that for group 2 (90%). No significant differences were detected between group 1 and group 2 for in vivo embryo development (number fetuses/transferred embryos in pregnant recipients; 33.3% v. 40%) or in vivo embryo survival (number viable fetuses/transferred embryos in pregnant recipients; 27.9% v. 33.9%). However, the in vivo efficiency (number viable fetuses/total transferred embryos) was higher (P<0.05) when transfers were performed with embryos from two donors (19.5% v. 30.5%). These results indicate that pooling embryos from two donors increases the in vivo efficiency after transfer of vitrified/warmed porcine blastocysts. This study was supported by grant from SENECA (FPI/99, Spain).


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 619-619 ◽  
Author(s):  
Kaldigul Smagulova

619 Background: Advances in molecular biology and a wide introduction to the practice of targeted therapies have improved outcomes and significantly affect the overall survival of patients. To investigate the efficacy and safety of bevacizumab (BEV) beyond first progression combined with chemotherapy (CT) in patients with metastatic colorectal cancer. Methods: 68 patients with mCRC who received chemotherapy treatment at the Department of the Kazakh Research Institute of Oncology and Radiology. Selecting second-line chemotherapy based on oxaliplatin or irinotecan depended of an earlier first-line therapy (FOLFOX, FOLFIRI). The survival rate was calculated by Kaplan-Meier, comparison of survival curves was performed by log-rank. Results: The study included 68 patients, who were randomized from February 2009 to November 2011(to 33 [48.5%] BEV + CT and 35 [51.5%] to CT alone). Analysis of the immediate results of treatment showed that in neither case was not achieved complete response of the tumor. Partial regression in group 1 – 11 (33.3 ± 8.2)%, and group 2 - in 9 (25.7 ± 7.3)%. Stabilization is achieved in 20 (60.6 ± 8.5)% and 23 (6.7 ± 8.0)% of cases, respectively. The progression of the disease was observed in the group 1 in 2 (6.1 ± 4.1)% and 3 (8.6 ± 4.7)% of cases. Median progression-free survival (PFS) and overall survival (OS) was 11.5 months (7-16) and 12.2 months in group 1, and 9.7 months (6-13.2) (PFS), 9.1 months(OS) in group 2, respectively. The adverse event profile was consistent with previously reported data for BEV + CT. BEV-related significant adverse events included bleeding grade 3-4 (1.5 %) and venous thrombosis (2.3 %). Conclusions: Our findings demonstrate that BEV + CT continued beyond progression significantly prolong OS and PFS in second-line therapy mCRC.


2021 ◽  
Vol 19 (2) ◽  
pp. 16-26
Author(s):  
V.N. Gorodin ◽  
◽  
D.L. Moysova ◽  
S.V. Zotov ◽  
A.A. Vanyukov ◽  
...  

Objective. To analyze polymorphisms of genes involved in hemostasis among patients with coronavirus disease 2019 (COVID 19) to improve the diagnosis of coagulopathy and prognosis of COVID-19 severity. Patients and methods. We have examined 52 patients with COVID-19 aged 33 to 84 years. Of them, 30 individuals (Group 1) were hospitalized with extremely severe (1A) and severe (1B) disease, whereas 22 patients with mild and asymptomatic disease were treated in outpatient departments (group 2). We assessed allelic variants of genes associated with hemostasis dysfunction (including FGB, FII, FV, FVII, F13A1, PAI-I, Gp1a, and Gp3a) using genomic DNA isolated from peripheral blood leukocytes. Polymorphisms were detected by polymerase chain reaction. Data analysis was performed using the Statistica, version 12 (StatSoft, USA). To compare independent categorical variables, we constructed contingency tables, performed Pearson chisquare test with Yates correction, Fisher exact test, and calculated relative risk (RR) [CI]. Results. COVID-induced coagulopathy (CAC) was diagnosed in 16.7% of patients; risk of CAC was identified in 30% of patients; sepsis-induced coagulopathy (SIC) was observed in 3.3% of patients; none of study participants had disseminated intravascular coagulation (DIC). Hemostasis impairments were more common in group 1A (RR = 2.28 [1.16–4.48]). Only patients from Group 1 had mutations in the gene encoding prothrombin (FII) –6.9% (RR = 1.78 [1.40–2.28]); protective polymorphisms in the FVII gene were more common in patients from Group 2 (χ2 = 3.28, р = 0.046); the rs 5985 polymorphism in the F13A1 gene was more common in patients from Group 1 (RR = 1.73 [1.06–2.82]). Patients with extremely severe COVID- 19 were more likely to have polymorphisms in the Gp1a gene (ITGA2) (RR =1.64 [1.05–2.56]) and F13A1 gene (χ2 = 2.67, р = 0.05), as well as homozygous mutation in the FII gene; they had no polymorphisms in the FVII gene (10976G→A). Thrombophilia, detected in 3 patients from Group 1, was a risk factor for thrombocytopenia (RR = 13.5 [3.56–51.23]), САС (RR = 9.0 [3.1–26.16]), and death (n = 4). The 4G allele (4G/4G, 4G/5G variants) in the PAI-I gene (rs 1799889), causing impaired fibrinolysis, was more frequently registered in patients with mild COVID-19 (91%) than in those with extremely severe COVID-19 (70%). It is possible that patients with extremely severe disease develop transient hyperfibrinolysis, which results in the transformation of local pulmonary COVID-19 into sepsis. Therefore, the 4G/4G and 4G/5G polymorphisms may have a protective role. Key words: hemostasis, COVID-19, polymorphism, genetics, COVID-induced coagulopathy


2006 ◽  
Vol 20 (3) ◽  
pp. 226-230 ◽  
Author(s):  
Diana Santana de Albuquerque ◽  
Luciana Ferraz Gominho ◽  
Roberto Alves dos Santos

The aim of this study was to evaluate histological aspects of the pulp-dentin complex of dogs submitted to pulpotomy and capped with ethyl-cyanoacrylate and calcium hydroxide. Thirty dog teeth were divided into 2 groups of 15 as follows: Group 1 - ethyl-cyanoacrylate; Group 2 - calcium hydroxide. The pulpotomies were carried out following all of the treatment precautions recommended for dogs. After 30 days the specimens were submitted to histological preparation and were then blindly evaluated by a histologist. Data were analyzed statistically by the Fisher exact test, comparing the two groups. After 30 days, the presence of a hard tissue barrier was observed in 83.3% of Group 1, and in 100% of Group 2 (p = 0.478). A continuous hard tissue barrier was observed in 50% of the ethyl-cyanoacrylate group and 75% of the calcium hydroxide group (p = 0.652). It can be concluded that both materials induced hard tissue barrier formation, but Group 2 had a higher percentage than Group 1, with no significant statistical differences; the differences observed between the different barriers (continuous/non-continuous) were not significant between groups and there was no pulpal necrosis in either group.


2021 ◽  
Author(s):  
Fernanda Oliveira Castilhos ◽  
Gabriel Cardozo Müller ◽  
Janete Vettorazzi ◽  
Daniela Vanessa Vettori ◽  
Maria Carolina Bittencourt Costa ◽  
...  

Abstract Background: Preterm premature rupture of amniotic membranes (PPROM) is responsible for about 30% of premature births, being associated with great neonatal morbidity and mortality. The use of antibiotics in expectant management seems to increase the latency period between PPROM and birth, as well as improving maternal and neonatal outcomes. However, short and long term benefits, and the ideal antibiotics regimen remains controversial. Objective: This study seeks to demonstrate that the use of antibiotics, with azithromycin as macrolide of choice, in expectant management reduces the birth rate in the first 48 hours after PPROM, increasing the latency period between PPROM and birth. Methods: Observational, retrospective cohort study in pregnant women with PPROM treated conservatively at the Hospital de Clínicas de Porto Alegre (HCPA), from January 2012 to December 2019. For the group that used antibiotics, the scheme was Azithromycin and Ampicillin for 48 hours, followed by Amoxicillin for 5 days, completing 7 days of treatment. Qualitative data was analyzed by Fisher exact test, and time to event analysis using Kaplan Meier estimator were used to evaluate latency to birth and Cox regression to estimate Hazard Rate. Results: 145 participants, of which 107 did not use antibiotics (group 1) and 38 used antibiotics (group 2). The 48-hour birth rate was significantly lower in the antibiotics group (33.6% in group 1 vs. 16% in group 2, p=0.04). The birth rate on patients presenting outcomes before 15 days presented a significant reduction (HR 0.6 [95% ICI 0.39 - 0.92]), as well median time to birth as seen in Kaplan Meier estimator by log-rank test. Conclusion: The use of this antibiotics regimen, with azithromicyn as macrolide of choice, reduced the birth rate in the first 48 hours, with potential clinical benefits due to the increase in the pharmacological window for corticosteroid action, among others, and increased median time to birth in first 15 days between PPROM and birth.


Author(s):  
I Putu Eka Jaya ◽  
Nyoman Mangku Karmaya ◽  
Made Jawi ◽  
Wayan Weta ◽  
Ida Bagus Ngurah ◽  
...  

Physical fitness is ability to perform the activity or activities without feeling tired excessively. Physical fitness associated with a person`s organs to carry out its tasks properly every day without experiencing significant fatigue. In a child’s mental retardation with a les mobile lifestyle that will affect his physical fitness. The purpose of this study to determine which type of gymnastic exercise better to the physical fitness on the students in Sekolah Dasar Luar Biasa Kuncup Bunga Denpasar.This research used experimental method using Randomized study Pre and Post Test Group Design. The subjects in this study were students in Sekolah Dasar Luar Biasa Kuncup Bunga Denpasar. There were 18 students which is divided into two groups: group-1 is senam penguins and group-2 is senam ria anak Indonesia. Data were obtained after a six-week training analyzed by paired t-test and unpaired t-test.The results of physical fitness test before training with Senam Penguins was 23.39 ± 1.69 and the test results after the training was 27.87 ± 3.28. the physical fitness test in group-2 before training with Senam Ria anak Indonesia was 22.69 ± 1.76 and the results after training was 24.64 ± 2.11. Paired t-test in both group before and after training showed significant differences after training in group-1 and group-2 with a value of p > 0.05 with an increase in physical fitness test results of (19.15) in group-1 and (8.64) in group-2. The percentage increase physical fitness test results of group-1 with senam penguins is higher than those in group-2 with senam ria anak Indonesia.So we can conclude that the training of senam penguin in Sekolah Dasar Luar Biasa Kuncup Bunga Denpasar improved the physical fitness test results higher than senam ria anak Indonesia.


2021 ◽  
pp. 105566562199265
Author(s):  
Ishwarya Shradha Mamidi ◽  
Esperanza Mantilla-Rivas ◽  
Brynne A. Ichiuji ◽  
Md Sohel Rana ◽  
Karen I. Ramirez ◽  
...  

Objective: Oronasal fistula (ONF) is a known complication after primary palatoplasty (PP). Studies investigating the effect of perioperative antibiotics on fistula rates after PP are limited by inadequate sample size or reliance on self-reporting through national databases. In this study, the authors evaluated the association between single-dose perioperative antibiotics and postoperative fistula rates after PP at a single institution. Design: A retrospective study. Participants: Children younger than 2 years who underwent PP from April 2009 to September 2019 were included. Interventions: Patients were divided into 2 categories: Group 1 received a single intraoperative dose of IV antibiotic, while group 2 did not. Main Outcome Measure(s): Outcome measures included ONF formation, length of stay (LOS), and 30-day readmission rates. Multivariable firth logistic regression, quantile regression, and χ2 tests were performed. Results: Of the 424 patients, 215 and 209 patients were in groups 1 and 2, respectively. The overall ONF rate was 1.9% among all patients. Patients in group 1 experienced an ONF rate of 3.3%, while patients in group 2 had an ONF rate of 0.5%. After correcting for confounding variables, the difference in ONF rates was not statistically different ( P = .68). Median LOS was 35.7 hours and 35.5 hours ( P = .17), while the rate of readmission within 30 days was 4.7% and 2.4% for group 1 and 2, respectively ( P = .96). Conclusions: Administration of a single-dose perioperative antibiotic did not decrease fistula formation after PP, nor did it affect the patient’s LOS or 30-day readmission rate.


2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Jai Patel ◽  
Mei Fong ◽  
Megan Jagosky

The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results.


Author(s):  
A H A Baazil ◽  
J G G Dobbe ◽  
E van Spronsen ◽  
F A Ebbens ◽  
F G Dikkers ◽  
...  

Abstract Objective This study aimed to compare the necessary scutum defect for transmeatal visualisation of middle-ear landmarks between an endoscopic and microscopic approach. Method Human cadaveric heads were used. In group 1, middle-ear landmarks were visualised by endoscope (group 1 endoscopic approach) and subsequently by microscope (group 1 microscopic approach following endoscopy). In group 2, landmarks were visualised solely microscopically (group 2 microscopic approach). The amount of resected bone was evaluated via computed tomography scans. Results In the group 1 endoscopic approach, a median of 6.84 mm3 bone was resected. No statistically significant difference (Mann–Whitney U test, p = 0.163, U = 49.000) was found between the group 1 microscopic approach following endoscopy (median 17.84 mm3) and the group 2 microscopic approach (median 20.08 mm3), so these were combined. The difference between the group 1 endoscopic approach and the group 1 microscopic approach following endoscopy plus group 2 microscopic approach (median 18.16 mm3) was statistically significant (Mann–Whitney U test, p < 0.001, U = 18.000). Conclusion This study showed that endoscopic transmeatal visualisation of middle-ear landmarks preserves more of the bony scutum than a microscopic transmeatal approach.


Hand ◽  
2018 ◽  
Vol 15 (4) ◽  
pp. 534-541 ◽  
Author(s):  
John C. Dunn ◽  
Kenneth R. Means ◽  
Sameer Desale ◽  
Aviram M. Giladi

Background: There are no clearly defined guidelines from hand surgical societies regarding preoperative antibiotic prophylaxis. Many hand surgeons continue to routinely use preoperative prophylaxis with limited supporting evidence. This study aimed to determine for which scenarios surgeons give antibiotics, the reasons for administration, and whether these decisions are evidence-based. Methods: An anonymous 25-question survey was e-mailed to the 921-member American Society for Surgery of the Hand listserv. We collected demographic information; participants were asked whether they would administer antibiotics in a number of surgical scenarios and for what reasons. Respondents were broken into 3 groups based on when they said they would administer antibiotics: Group 1 (40 respondents) would give antibiotics in the case of short cases, healthy patients, without hardware; group 2 (9 respondents) would not give antibiotics in any scenario; and group 3 (129 respondents) would give antibiotics situationally. The Fisher exact test compared demographic variables, frequency of use, and indications of antibiotic prophylaxis. Results: Of the 921 recipients, 178 (19%) responded. Demographic variables did not correlate with the antibiotic use group. Operative case time >60 minutes, medical comorbidity, and pinning each increased antibiotic use. Group 1 respondents were more likely to admit that their practice was not evidence-based (74.4%) and that they gave antibiotics for medical-legal concern (75%). Twenty-two percent of respondents reported seeing a complication from routine prophylaxis, including Clostridium difficile infection. Conclusions: Antibiotics are still given unnecessarily before hand surgery, most often for medical-legal concern. Clear guidelines for preoperative antibiotic use may help reduce excessive and potentially inappropriate treatment and provide medical-legal support.


Sign in / Sign up

Export Citation Format

Share Document