Indications for sexology consultation in women after surgical treatment due to breast cancer

Introduction and objectives. Surgical treatment due to brest cancer have an impact on women sexuality. There is a need for research about effective indications for sexology consultation in women after such treatment. The aim of this study is to determine the indications for sexology consultation in women after surgical treatment for breast cancer. Materials and method. We tested 42 women patients diagnosed with breast cancer who had undergone mastectomy 3 months before the study. 3 months after the surgery the women were surveyed using the Polish version of FSFI assessing sexual functioning in women. The result of PL-FSFI were compared with the control group. Results. It was found that the mean score of PL-FSFI in the study group 3 months after the surgery was 13.33 points (score range: 1.2–31.7; median 8.3 points) with a statistically significant difference in terms of areas: desire, arousal, lubrication and orgasm in favour of the control group. The total score of PL-FSFI was significantly lower in women after mastectomy than in women after breast-conserving surgery. It has been shown that sexually active women in whom the surgery concerned the right breast (on the side of the dominant hand) scored lower on the scale “sexual functioning” of QLQ-BR-23 than women with surgery of the left breast, with this difference being statistically significant. There was a statistically significant correlation between the baseline performance status on the Zubrod scale and the scales: desire, lubrication and satisfaction of PL-FSFI. Living in a small town proved to be statistically significant for predicting a lower risk of sexual dysfunction among the surveyed women. Conclusions. The women who underwent surgery due to breast cancer had a higher risk of sexual dysfunction compared to the general population. Higher risk of sexual dysfunction especially concerns women after mastectomy, those who underwent breast surgery on the side of the dominant hand, and those with a worse preoperative overall level of functioning of ≥ 1 point on the Zubrod scale. A lower risk of disorders was observed in women living in smaller towns. The above factors indicate the advisability for sexology consultation in women with breast cancer

Evaluation of quality of life in women with breast cancer, with particular emphasis on sexual satisfaction, future perspectives and body image, depending on the method of surgery

Introduction. Both because of the large number of women undergoing surgery and a high cure rates, psychological rehabilitation of the consequences of breast cancer and side effects of their treatment is a major challenge of modern psycho-oncology. Aim. The study analyzed the quality of life in women with breast cancer, with particular emphasis on indicators of sexual satisfaction, future perspectives and body image, depending on the method of surgery. Method. The study included 42 women aged 35–70 years, 3 months after surgery due to early breast cancer, treated with adjuvant chemotherapy. The following research tools were used in the study: two EORTC questionnaires: QLQ-C30, BR23, and sexual function questionnaire: PL-FSFI. Results. There was no significant difference in the overall quality of life, depending on the type of surgery. The greatest local complaints were reported by patients after breast conserving surgery (BCT) with axillary lymphadenectomy. A higher level of cognitive functioning but a greater severity of systemic side effects was found in women undergoing mastectomy compared to BCT-patients. Women who underwent surgery of the right breast reported increased problems in sexual functioning (p = 0.034). Multiple regression analysis showed a positive correlation of the emotional functioning variable with the assessment of future perspectives (p = 0.01) and body image (p = 0.007). Conclusions. The type of surgical technique does not affect the overall quality of life and sexual satisfaction. Problems with memory and attention do not correlate directly with the side effects, and as such require an independent diagnostics. Women undergoing treatment of the dominant-side breast should be the candidates for sexology consultation. There is a risk of disturbances in the body image and in the assessment of future perspectives in patients with emotional disorders observed within 3 months after surgery

Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in women with low-risk breast cancer : results of a prospective randomized study

Background: Anthracycline‑induced cardiotoxicity (AIC) remains the main long‑term irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of the most reasonable approaches. Aims: In this prospective randomized open‑label study, we aimed to verify whether ramipril protects from early‑onset AIC in women with breast cancer (BC). Methods: We analyzed data from 96 women (median age, 47 years) with BC after breast surgery, without significant cardiovascular diseases, who were eligible for adjuvant anthracyclines. They were randomized to a ramipril or control arm. Cardiotoxicity was estimated with repeat echocardiography and themeasurement of troponin I and N‑terminal fragment of the prohormone brain natriuretic peptide (NT‑proBNP) levels over 1‑year follow‑up. Anthracycline‑induced cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF), elevated biomarker levels, and/or occurrence of heart failure (HF) or cardiac death. Results: A decrease in LVEF above 10‑percent points occurred in 6.3% of ramipril patients and 18.5% ofcontrols (P = 0.15). No cases of HF, cardiac death, or LVEF decline below 50% were reported. The percentage of patients with elevated NT‑proBNP levels increased with time in controls (P = 0.003) and remained unchanged in the ramipril arm. At the end of follow‑up, an increase in NT‑proBNP levels was more common and decline was less common in the control than ramipril arm (P = 0.01). No significant differences in troponin levels were found between the study arms. Ramipril was well tolerated in normotensive women. Conclusions: In relatively young women with BC without serious comorbidities, who received anthracyclines, 1‑year treatment with ramipril exerts potentially protective effects on cardiotoxicity assessed with NT‑proBNP levels

The relationship between surgical treatment (mastectomy vs. breast conserving treatment) and body acceptance, manifesting femininity and experiencing an intimate relation with a partner in breast cancer patients

Aim. The aim of the study was to verify the following hypotheses: (1) Do women who have undergone surgical treatment for breast cancer differ from healthy women in the way they experience their body (body self)?; (2) Does the surgical technique (mastectomy vs. breast conserving treatment) differentiate the group in terms of experiencing their body after the surgery?; (3) Do demographic variables, BMI, breast size and the evaluation of the scar differentiate the group in terms of experiencing their body self after the surgery? Method. In order to gain some insight into how women experience their body after breast surgery, the Body Self Questionnaire designed in 2005 by Beata Mirucka was used. The analysis included data from 50 women who completed surveys. This data were compared to the control group. Data were analyzed using IBM SPSS Statistics package, version 24, with a one-way analysis of variance (ANOVA). Results. Statistically significant differences were obtained between the entire group of women after breast surgery (mastectomy and BCT, jointly) and the control group of healthy women in three aspects of the Body Self Questionnaire: body acceptance, manifesting femininity and experiencing an intimate relation with a partner. Conclusions. Surgical treatment of breast cancer is significantly associated with the way patients experience their body, which is expressed in three dimensions of the body self in treated women

A novel MMP12 locus is associated with large artery atherosclerotic stroke using a genome-wide age-at-onset informed approach.

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10⁻⁷), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10⁻⁸). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10⁻¹⁵; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS

Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke

Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-tage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 1549 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r(2)>= 0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-ge Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.Peer reviewe

Genetic variation at 16q24.2 is associated with small vessel stroke.

OBJECTIVE: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. METHODS: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. RESULTS: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10-1.22]; p = 3.2 × 10-9 ). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05-1.16]; p = 5.3 × 10-5 ; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84-1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10-7 ) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10-6 ). INTERPRETATION: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. Ann Neurol 2017;81:383-394.Matthew Traylor is funded by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by NIHR Comprehensive Biomedical Research Unit funding awarded to Cambridge University Hospitals Trust. Cathryn Lewis receives salary support from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Collection of the UK Young Lacunar Stroke DNA Study (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples was supported by a Stroke Association Grant (TSA 2013/01). Robin Lemmens is a senior clinical investigator of FWO Flanders. Martin Dichgans received funding from the DFG (CRC 1123, B3) and a EU Horizon 2020 grant (agreement No 666881 SVDs@target). The TwinsUK study was funded in part by the European Research Council (ERC 250157), and from the TwinsUK resource, which receives support from the Wellcome Trust and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. SNP Genotyping was performed by The Wellcome Trust Sanger Institute and National Eye Institute via NIH/CIDR. The SiGN study was funded by a cooperative agreement grant from the US National Institute of Neurological Disorders and Stroke, National Institutes of Health (U01 NS069208)

Panitumumab w leczeniu chorych na uogólnionego raka jelita grubego

Panitumumab is a fully human monoclonal IgG2 antibody approved for the treatment of metastatic colorectal cancer (mCRC). Efficacy of the panitumumab was proven in combination with chemotherapy in the first line of mCRC therapy and as a monotherapy after failure of standard chemotherapy with oxaliplatin, 5-fluorouracil and irinotecan. 2,3,4 exon of KRAS/NRAS and BRAF gene testing with negative mutation status is required before introducing panitumumab. Skin toxicity represents typical adverse events of EGFR blockers and does not limit the effectiveness of the antibody. Panitumumab is an important element of mCRC therapy due to its positive impact on prognosis, favorable toxicity profile and presence of predictive biomarkers enabling initial selection of patients potentially responding to the treatment.Panitumumab jest ludzkim przeciwciałem monoklonalnym klasy IgG2 zarejestrowanym w terapii chorych na przerzutowego raka jelita grubego. Skuteczność leku potwierdzono podczas stosowania w skojarzeniu z chemioterapią w I linii leczenia zaawansowanego raka jelita grubego oraz w monoterapii po niepowodzeniu schematów zawierających oksaliplatynę, irynotekan oraz fluorouracyl. Warunkiem zastosowania panitumumabu jest wykluczenie obecności mutacji w eksonach 2., 3. i 4. genów KRAS i NRAS oraz mutacji aktywującej (V600E) w genie BRAF. Toksyczność jest typowa dla leków blokujących receptor naskórkowego czynnika wzrostu (EGFR, epidermal growth factor receptor) i nie stanowi czynnika ograniczającego wartość leczenia. Panitumumab ma ugruntowane miejsce w leczeniu chorych na uogólnionego raka jelita grubego z uwagi na znaczący wpływ na poprawę rokowania, korzystny profil bezpieczeństwa oraz dostępność biomarkerów predykcyjnych umożliwiających dobór chorych odnoszących korzyść z leczenia