Clinical characteristics and anti-PD-(L)1 treatment outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9596-9596
Author(s):  
Kathryn Cecilia Arbour ◽  
Hira Rizvi ◽  
Andrew J. Plodkowski ◽  
Darragh Halpenny ◽  
Matthew David Hellmann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Clinical Characteristics ◽  
Cox Proportional Hazards Model ◽  
Smoking History ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Baseline Characteristics ◽  
Direct Inhibitors

9596 Background: KRAS mutations are identified in approximately 30% of NSCLC. There are no FDA approved targeted therapies for patients with KRAS-mutant non-small cell lung cancer (NSCLC) but novel direct inhibitors of KRAS G12C have shown some activity in early phase clinical trials. We hypothesized that patients with KRAS-G12C mutations may have distinct clinical characteristics and responses to systemic therapies compared to patients with non-G12C subtypes. Methods: We identified patients with KRAS-mutant lung cancers who underwent next-generation sequencing with MSK-IMPACT, between January 2014 and December 2018. Baseline characteristics were compared with the Chi-square and Fisher’s exact test for categorical data and Wilcoxon rank-rum test for continuous data. Overall survival was calculated from time of diagnosis of metastatic/recurrent disease to date of death or last follow up, with left truncation to account for time of MSK-IMPACT. Overall survival was compared between groups using the Cox proportional-hazards model. Response evaluations where performed by independent thoracic radiologists according to RECIST 1. and compared between group with the Fisher’s exact test. Results: We identified 1194 patients with KRAS -mutant NSCLC, 772 with recurrent or metastatic disease. Of patients with advanced disease, 46% (352/772) had mutations in KRAS-G12C and 54% harbored non-G12C mutations (15% G12D, 16% G12V, 8% G12A, 4% G13D). Co-mutation patterns were similar with respect to KEAP1 (p=0.9) and STK11 (p=1.0). Patients with non-G12C mutations had a higher proportion of never smokers (10% vs 1.4% p<0.001). The median OS from diagnosis was 13 months for G12C and non-G12C patients (p=0.99). 45% (347/772) received 1L or 2L line treatment with PD-(L)1 inhibitor. RECIST measurements were available for 290/347 cases (84%). ORR with anti-PD-(L)1 treatment was 24% vs 28% in G12C vs non-G12C patients (p=0.5). In patients with PD-L1 50% (n=103), ORR was 39% for G12C vs 58% non-G12C patients (p=0.06). Conclusions: KRAS G12C mutations are present in 12% of patients with NSCLC and represent a relevant subtype of NSCLC given KRAS G12C inhibitors now in clinical development. Baseline characteristics including co-mutation patterns are similar between patients with G12C and non-G12C, except for smoking history. The efficacy of KRAS G12C direct inhibitors will need to be compared to other available therapies for KRAS mutant NSCLC (chemotherapy and PD-(L)1 inhibitors) to identify most effective therapeutic strategy.

Chemo-immunotherapy outcomes of KRAS-G12C mutant lung cancer compared to other molecular subtypes of KRAS-mutant lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9088-9088
Author(s):  
Kathryn Cecilia Arbour ◽  
Biagio Ricciuti ◽  
Hira Rizvi ◽  
Matthew D. Hellmann ◽  
Helena Alexandra Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Proportional Hazards Model ◽  
Unmet Need ◽  
Clinical Development ◽  
Response To Therapy ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test

9088 Background: KRAS mutations are identified in approximately 30% of NSCLC, with G12C mutations being the most common subtype and representing 12% of all non-small cell lung cancer cases. Novel direct inhibitors are in clinical development and have shown promising activity, although the efficacy of these agents compared to other standard therapies for lung cancer is not yet known. We hypothesized that patients with KRAS-G12C mutations may have distinct responses to chemo-immunotherapy regimens both with respect to STK11 and KEAP1 co-mutation status and compared to patients with non-G12C subtypes. Methods: Patients with KRAS-mutant lung cancers at Memorial Sloan Kettering Cancer Center and Dana Farber Cancer Institute treated with chemo-immunotherapy regimens as first line therapy for advanced/metastatic disease were identified. Subset with KRAS G12C mutations non-G12C subtypes were compared and response to therapy was assessed by investigator. Baseline characteristics were compared with the Chi-square and Fisher’s exact test for categorical data and Wilcoxon rank-rum test for continuous data. Response evaluations where performed by investigators and compared between groups with the Fisher’s exact test. Progression free survival and overall survival was calculated from start of therapy to date of progression or death/last follow up, respectively and compared between groups using the Cox proportional-hazards model. Results: We identified 137 patients with KRAS -mutant NSCLC treated with chemo-immunotherapy: 45% (62/137) had mutations in KRAS-G12C and 55% harbored non-G12C mutations (17% G12V, 15% G12D, 4% G12A, 4% G12S, 3% G13D). The median OS was 21 and 14 months for G12C and non-G12C patients, respectively (p = 0.24). ORR to chemo-immunotherapy for patients harboring a KRAS-G12C mutation was 40% (25/62) compared to 31% (23/75) in non-G12C subtypes (p = 0.3). Median PFS was similar for both G12C and non-G12C subtypes (7.3 vs 6.1 months, respectively, p = 0.12). Concurrent STK11 mutation was identified in 40% of patients with KRAS-G12C and KEAP1 alterations were observed in 32% of patients. In patients with KRAS-G12C, co-mutation in STK11 and/or KEAP1 was associated with shorter PFS (15.8 vs 5.1 months, p = 0.01). Conclusions: KRAS-G12C mutations are present in 12% of patients with NSCLC and represent a relevant subtype of NSCLC given KRAS G12C inhibitors now in clinical development. Treatment outcomes to chemo-immunotherapy are similar in patients with G12C and non-G12C subtypes. Outcomes are poor for patients with concurrent STK11 and/or KEAP1 mutations representing a significant unmet need.

scholarly journals Clinical Characteristics of Patients With Lung Adenocarcinomas Harboring BRAF Mutations

2011 ◽  
Vol 29 (15) ◽  
pp. 2046-2051 ◽  
Author(s):  
Paul K. Paik ◽  
Maria E. Arcila ◽  
Michael Fara ◽  
Camelia S. Sima ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Clinical Characteristics ◽  
Median Overall Survival ◽  
Smoking History ◽  
Egfr Mutations ◽  
Braf Mutations ◽  
Former Smokers ◽  
Lung Adenocarcinomas

Purpose BRAF mutations occur in non–small-cell lung cancer. Therapies targeting BRAF mutant tumors have recently been identified. We undertook this study to determine the clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. Patients and Methods We reviewed data from consecutive patients with lung adenocarcinoma whose tumors underwent BRAF, EGFR, and KRAS mutation testing as well as fluorescence in situ hybridization for ALK rearrangements. Patient characteristics including age, sex, race, performance status, smoking history, stage, treatment history, and overall survival were collected. Results Among 697 patients with lung adenocarcinoma, BRAF mutations were present in 18 patients (3%; 95% CI, 2% to 4%). The BRAF mutations identified were V600E (50%), G469A (39%), and D594G (11%). Mutations in EGFR were present in 24%, KRAS in 25%, and ALK translocations in 6%. In contrast to patients with EGFR mutations and ALK rearrangements who were mostly never smokers, all patients with BRAF mutations were current or former smokers (P < .001). The median overall survival of advanced-stage patients with BRAF mutations was not reached. In comparison, the median overall survival of patients with EGFR mutations was 37 months (P = .73), with KRAS mutations was 18 months (P = .12), and with ALK rearrangements was not reached (P = .64). Conclusion BRAF mutations occur in 3% of patients with lung adenocarcinoma and occur more commonly in current and former smokers. The incidence of BRAF mutations other than V600E is significantly higher in lung cancer than in melanoma.

Racial diversity of genomic alterations in lung adenocarcinomas.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9543-9543
Author(s):  
Huashan Shi ◽  
Fei Heng ◽  
Kexun Zhou ◽  
Ruqin Chen ◽  
Rami Manochakian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Native American ◽  
The United States ◽  
Genomic Alteration ◽  
Racial Groups ◽  
Genomic Alterations ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Therapeutic Decisions ◽  
Fisher’S Exact Test

9543 Background: Lung cancer is the leading cause of cancer related death in the United States in all racial groups. However, the overall death rate from lung cancer is different among white, black and Asian. Although differences in socioeconomic status and treatments received might be the contributing factors, the biology, particularly genomic alteration of cancer might also have an important impact. To date, the differences of genomic alterations among all racial patients are poorly understood. Methods: The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE, version 7.0) database was analyzed. A total of 8908 patients with lung adenocarcinoma (LUAD) were identified. Among them, 5652 patients who had comprehensive sequencing results (gene panel ≥ 275) were selected for further analysis. Patients with unknown race, undefined and Pacific Island (only 3 patients) were excluded. Finally, 5360 patients were included in the study. The prevalence and distribution of genomic alteration cross all racial groups were analyzed. Results: Overall 5951 samples from 5360 patients were collected (85.7% white, 7.9% Asian, 4.7% black, 0.2% Native American and 1.4% other). Most patients have only one sample. The median mutation counts in white, black, Asian, Native American and others are 7, 6, 5, 5, 7 respectively (Kruskal–Wallis test, P< 0.001). Asian have significantly higher rates of insertion and deletions than other races (14.8% of Asian versus 9.8% of white, 10.7% of black, 10.4% of Native American, 11.1% of other; Pearson’s chi-square test, < 0.001). TP53, EGFR, KRAS and STK11 are the most frequent alterations in white, black and other. EGFR, TP53, KRAS and APC are the most frequent alterations in Asian. STK11 mutations are rare in both Asian and Native American. Native Americans have more alterations of LRP1B, ARID2 and ATM, although the patients’ number remains small. ATM and KEAP1 mutations are also common in white and black. EGFR is the highest discrepancy gene in racial distribution. 78.9% Asian, 47.7% black, 36.4% of native American had EGFR alteration in comparison to 29.6% in white (Fisher's exact test, P < 0.001). KRAS is the second highest discrepancy gene in racial distribution. 11.6% Asian, 26.3% black, 27.3% of Native American had KRAS alteration in comparison to 36.1% in white (Fisher's exact test, P< 0.001). Conclusions: Our study demonstrated the potential diversity of genomic alterations across all racial groups with potential impact on therapeutic decisions.

Elevated D-Dimer Level Is a Predictor of Poor Survival Even in Patients without Venous Thromboembolism (VTE).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4020-4020
Author(s):  
S. Bacchu ◽  
Shankaranarayana Paneesha ◽  
K. French ◽  
E. Cheyne ◽  
Anton Borg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Venous Thrombosis ◽  
P Value ◽  
Poor Survival ◽  
Exact Test ◽  
Cox Regression Analysis ◽  
Fisher's Exact Test ◽  
Underlying Malignancy ◽  
Fisher’S Exact Test ◽  
D Dimer

Abstract Use of D-dimer levels along with clinical probability scores in the diagnosis of venous thrombosis is well established. Recently it has been shown that high quantitative D-dimer levels at presentation are predictor for poor survival and underlying malignancy in patients with VTE. Do quantitative D-dimer levels in patients without VTE have a similar predictive role? Materials and Methods This study included 2263 (F: 1518; M: 745) consecutive patient episodes from the prospectively maintained database of patients without venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients with suspected venous thrombosis underwent a Doppler ultrasound examination to rule out venous thrombosis. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review. Statistical analysis was carried out using SPSS 13.0 for Windows and GraphPad InStat ® Version 3.06 for Windows software’s. Overall survival (OS) was estimated by the Kaplan-Meier method. Cox regression analysis by forward Likelihood Ratio was subsequently used to explore the independent effect of variables that showed a significant influence on OS. Results Median age at diagnosis was 69 yrs (range: 18–105 yrs). Median D-dimer level was 1000ug FEU/ml (range: 300–35500ug FEU/ml). 1165 patients (51.7%) had a D-dimer level of &gt;1000ug FEU/ml and 40 (2%) had a D-dimer level of &gt;8000ug FEU/ml at presentation. 1472 patients (65.4%) were aged above 60 years. Median follow up was 22 months (range: 0–65 months). D-dimer level &gt;1000ug FEU/ml, &gt;4000ug FEU/ml and &gt;8000ug FEU/ml were associated with decreased overall survival (Log rank test: p value: 0.002, &lt; 0.001 and &lt;0.001 respectively). Age&gt;60 yr is also associated with decreased overall survival (Log rank test: p value: &lt;0.001). D-dimer &gt;8000ug FEU/ml and age&gt;60yr were an independent poor prognostic factor for overall survival on Cox regression analysis (p value: &lt;0.001). 27.5% of patients with a D-dimer level &gt;8000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.003). 17% of patients with a D-dimer level &gt;4000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.04). 12.4% of patients with a D-dimer level &gt;1000ug FEU/ml had cancer (Fisher’s exact test; p value: 0.02). Conclusions This study show elevated D-dimer levels at presentation in patients without venous thrombosis is a marker of poor survival and a predictor for underlying malignancy. We have previously shown that D-dimer &gt;8000ug FEU/ml is a predictor for poor survival and underlying malignancy in patients with proven venous thrombosis. This suggests heightened fibrinolytic activity in the absence or presence of established venous thrombosis is associated with poor prognosis. Further studies are warranted to establish in different medical conditions the presence or absence of increased fibrinolysis and impact on clinical outcome.

Retrospective review of treatment for angiosarcoma at Fox Chase Cancer Center over the past 15 years

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10034-10034 ◽  
Author(s):  
S. Saroha ◽  
S. Litwin ◽  
M. von Mehren
Keyword(s):  
Overall Survival ◽  
Chemotherapeutic Agents ◽  
Weekly Paclitaxel ◽  
Cancer Center ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
The Past ◽  
Response To Chemotherapy ◽  
Fisher’S Exact Test ◽  
Anatomic Locations

10034 Background: Angiosarcoma is a rare vascular neoplasm that may arise in a variety of anatomic locations. There is limited published data on chemotherapy treatment in angiosarcoma and data on taxane therapy does not utilize contemporary schedules. We present a retrospective analysis of our institution's experience with angiosarcoma over the past 15 years. We reviewed patient characteristics, overall survival and response to various chemotherapeutic agents. We specifically compared the response to weekly paclitaxel with all other chemotherapeutic agents used over the study period. Methods: Medical records of all the patients treated with the diagnosis of angiosarcoma at Fox Chase Cancer Center between January 1990 and June 2005 were reviewed. Overall survival was determined by the Kaplan-Meier method. Response to chemotherapy was determined at two-month follow-up after starting treatment. Clinician judgment was used to define response for superficial lesions. We compared the response to weekly paclitaxel with all other chemotherapy regimens using Fisher's exact test. p <0.10 was considered significant. Results: A total of 39 patients were identified. Most common sites for angiosarcoma were head and neck (including scalp) and breast. Median overall survival was 21 months. Since many patients received several lines of chemotherapy, 40 chemotherapy administrations were identified for analysis. 10 of 13 patients showed response to weekly paclitaxel versus 14 of 27 for non-paclitaxel regimens, which was not statistically significant by Fisher's exact test (2-tail, p=0.18). We also analyzed the response with respect to different anatomic locations of angiosarcoma and individual chemotherapy regimens used, however the numbers were too small for statistical comparisons. Conclusions: Angiosarcoma is an aggressive malignancy with poor survival rates. Our study demonstrated that paclitaxel has efficacy in angiosarcoma, although not statistically superior to non-taxane containing regimens. No significant financial relationships to disclose.

scholarly journals TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Edaise M. da Silva ◽  
Pier Selenica ◽  
Mahsa Vahdatinia ◽  
Fresia Pareja ◽  
Arnaud Da Cruz Paula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Genetic Alterations ◽  
Wild Type ◽  
Histologic Subtype ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Hotspot Mutations ◽  
Or Gene

AbstractMetaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher’s exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher’s exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers.

scholarly journals Association of P10L Polymorphism in Melanopsin Gene with Chronic Insomnia in Mexicans

2021 ◽  
Vol 18 (2) ◽  
pp. 571
Author(s):  
Bianca Ethel Gutiérrez-Amavizca ◽  
Ernesto Prado Montes de Oca ◽  
Jaime Paul Gutiérrez-Amavizca ◽  
Oscar David Castro ◽  
Cesar Heriberto Ruíz-Marquez ◽  
...  
Keyword(s):  
Statistical Power ◽  
Medical Condition ◽  
Severity Index ◽  
Recessive Model ◽  
Chronic Insomnia ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Increased Risk ◽  
Fisher’S Exact Test ◽  
And Function

The aim of this pilot study was to determine the association of the P10L (rs2675703) polymorphism of the OPN4 gene with chronic insomnia in uncertain etiology in a Mexican population. A case control study was performed including 98 healthy subjects and 29 individuals with chronic insomnia not related to mental disorders, medical condition, medication or substance abuse. Samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genetic analyses showed that the T allele of P10L increased risk to chronic insomnia in a dominant model (p = 1 ×10−4; odds ratio (OR) = 9.37, CI = 8.18–335.66, Kelsey statistical power (KSP) = 99.9%), and in a recessive model (p = 7.5 × 10−5, OR = 9.37, KSP = 99.3%, CI = 2.7–34.29). In the insomnia group, we did not find a correlation between genotypes and chronotype (p = 0.219 Fisher’s exact test), severity of chronic insomnia using ISI score (p = 0.082 Fisher’s exact test) and ESS score (p ˃ 0.999 Fisher’s exact test). However, evening chronotype was correlated to daytime sleepiness severity, individuals with an eveningness chronotype had more severe drowsiness according to their insomnia severity index (ISI) score (p = 0.021 Fisher’s exact test) and Epworth sleepiness scale (ESS) score (p = 0.015 Fisher’s exact test) than the morningness and intermediate chronotype. We demonstrated that the T allele of the P10L polymorphism in the OPN4 gene is associated with chronic insomnia in Mexicans. We suggest the need to conduct larger studies in different ethnic populations to test the probable association and function of P10L and other SNPs in the OPN4 gene and in the onset of chronic insomnia.

scholarly journals Detection of AZF microdeletions and reproductive hormonal profile analysis of infertile sudanese men pursuing assisted reproductive approaches

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hassan Osman Alhassan Elsaid ◽  
Tarteel Gadkareim ◽  
Tagwa Abobakr ◽  
Eiman Mubarak ◽  
Mehad A. Abdelrhem ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Klinefelter Syndrome ◽  
Semen Analysis ◽  
Control Group ◽  
Male Factor ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Infertile Men ◽  
Significant Difference ◽  
Fisher’S Exact Test

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.

Επίδραση αναλόγου της προστακυκλίνης στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού

2012 ◽  
Author(s):  
Γεώργιος Γαλανόπουλος
Keyword(s):  
Analysis Of Variance ◽  
Anova Analysis ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Significant Difference ◽  
Fisher’S Exact Test

Στόχος της παρούσας διδακτορικής διατριβής ήταν η πειραματική μελέτη της επίδρασης της ιλοπρόστης (ανάλογο της προστακυκλίνης) στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού. Για τη μελέτη χρησιμοποιήθηκαν 80 άρρενες επίμυες, οι οποίοι χωρίστηκαν τυχαιοποιημένα σε 4 (1, 2, 3, 4) ομάδες, με 2 (α, β) ισοδύναμες υποομάδες έκαστη. Στην ομάδα 1 (ελέγχου) και 3 (ιλοπρόστη) διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Στην ομάδα 2 (ειλεός) και 4 (ειλεός και ιλοπρόστη) επιτεύχθηκαν αρχικά συνθήκες αποφρακτικού ειλεού και 24 ώρες μετά διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Η ιλοπρόστη χορηγήθηκε στις ομάδες 3 και 4 σε δόση 2μg/kg Β.Σ. σε 3ml διαλύματος NaCl 0,9% ενδοπεριτοναϊκά, διεγχειρητικά και κάθε ημέρα μέχρι τη θυσία, ενώ αντίστοιχα στις ομάδες 1 και 2 στα πειραματόζωα χορηγούνταν 3ml διαλύματος NaCl 0,9%. Σε κάθε ομάδα τα μισά πειραματόζωα (υποομάδα 1α, 2α, 3α, 4α) θυσιάστηκαν την 4η μετεγχειρητική ημέρα και τα υπόλοιπα (υποομάδα 1β, 2β, 3β, 4β) την 8η. Κατά τη νεκροτομή γινόταν μακροσκοπικός έλεγχος για ρήξη της αναστόμωσης, ύπαρξη περιτονίτιδος ή περιαναστομωτικού αποστήματος καθώς και ποσοτική αξιολόγηση των συμφύσεων σύμφωνα με την κλίμακα Van der Hamm. Ακολουθούσε μέτρηση της πίεσης διάσπασης και στη συνέχεια τμήμα της αναστόμωσης αποστέλλονταν για ιστολογική εξέταση κατά την οποία αξιολογούνταν η φλεγμονώδης αντίδραση (διήθηση από ουδετερόφιλα), η νεοαγγειογένεση, ο αριθμός των ινοβλαστών και η εναπόθεση νεοκολλαγόνου. Η ταξινόμηση των μικροσκοπικών ευρημάτων έγινε σύμφωνα με την κλίμακα Ehrlich και Hunt με τις τροποποιήσεις κατά Phillips. Επιπλέον, προσδιορίστηκε βιοχημικά η συγκέντρωση υδροξυπρολίνης και κολλαγενάσης I επί της αναστόμωσης. Για την συνοπτική παρουσίαση των αποτελεσμάτων υπολογίστηκαν απόλυτες και σχετικές συχνότητες (ποσοστά %), δείκτες κεντρικής τάσης (μέσοι όροι, διάμεσες τιμές) και δείκτες διασποράς (ελάχιστες τιμές, μέγιστες τιμές, τυπικές αποκλίσεις). Για τη σύγκριση των μέσων όρων χρησιμοποιήθηκε το κριτήριο της Ελάχιστης Σημαντικής Διαφοράς (Least Significant Difference-LSD), μετά από την εφαρμογή της μεθόδου ANOVA (Analysis of Variance). Για τις συγκρίσεις των ποσοστών, εφαρμόστηκε ο ακριβής έλεγχος του Fisher (Fisher’s Exact Test). Από την ανάλυση των πειραματικών δεδομένων προέκυψε ότι η ενδοπεριτοναϊκή χορήγηση ιλοπρόστης σε συνθήκες αποφρακτικού ειλεού, έχει ως αποτέλεσμα τον περιορισμό της αρνητικής δράσης του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου. Συγκεκριμένα, την 4η και 8η μετεγχειρητική ημέρα ελαττώνει σημαντικά την απώλεια σωματικού βάρους. Επίσης, προάγει τη νεοαγγειογένεση, ενώ συγχρόνως αυξάνει τον πολλαπλασιασμό των ινοβλαστών και τη συγκέντρωση υδροξυπρολίνης. Επιπλέον, την 4η μετεγχειρητική ημέρα ελαττώνει τη φλεγμονώδη αντίδραση και μειώνει τη συγκέντρωση κολλαγενάσης Ι. Σταδιακά, την 8η μετεγχειρητική ημέρα αυξάνει τη σύνθεση νεοκολλαγόνου στην περιοχή της αναστόμωσης. Οι παραπάνω δράσεις έχουν ως αποτέλεσμα την αύξηση της μηχανικής ισχύος των αναστομώσεων, κατά την 4η και 8η μετεγχειρητική ημέρα, όπως αυτή προκύπτει από τη μέτρηση των πιέσεων διάσπασης. Συμπερασματικά, η άμεση μετεγχειρητική ενδοπεριτοναϊκή χορήγηση ιλοπρόστης ενισχύει τους μηχανισμούς επούλωσης και αντισταθμίζει την αρνητική δράση του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου.

scholarly journals Efficiency of small mammal trapping in an Atlantic Forest fragmented landscape: the effects of trap type and position, seasonality and habitat

2014 ◽  
Vol 74 (3) ◽  
pp. 538-544 ◽  
Author(s):  
ALM Vieira ◽  
AS Pires ◽  
AF Nunes-Freitas ◽  
NM Oliveira ◽  
AS Resende ◽  
...  
Keyword(s):  
Ground Level ◽  
Fragmented Landscape ◽  
Pitfall Traps ◽  
Exact Test ◽  
Future Studies ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test ◽  
Trapping Methods ◽  
Mammal Communities ◽  
Total Effort

Trapping methods can strongly influence the sampling of mammal communities. This study compared the efficiency of the capture of small mammals in Sherman traps in two positions (at ground level and in trees) and pitfall traps in a fragmented landscape. Trapping sessions were carried out between October 2008 and October 2009 at two fragments (8 and 17 ha), an agroforest corridor between them, and the adjacent pasture. A total effort of 4622 trap-nights resulted in 155 captures of 137 individuals from six species. Pitfalls had greater success (4.03%), followed by Shermans on the ground (2.98%) and on trees (2.37%; χ2= 6.50, p = 0.04). Five species were caught in Sherman ground traps, four in pitfalls and just two on trees. There was no difference among trap types for marsupials (χ2 = 4.75; p = 0.09), while for rodents, pitfalls were more efficient than Shermans on the ground (Fisher's exact test, p = 0.02). As a result, the efficiency of each trap type differed among habitats, due to differences in their species composition. Pitfalls were more efficient in the rainy season (Fisher's exact test, p <0.0001) while Shermans on trees were more efficient in the dry season (Fisher's exact test, p = 0.009). There was no difference between seasons for Shermans on the ground (Fisher's exact test, p = 0.76). Considering the results found, we recommend that future studies of forest mammal communities, particularly those designed to test the effects of forest fragmentation, include combinations of different trap types.

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