Somatic mutations in BRCA1&2 in 201 unselected ovarian carcinoma samples - single institution study.

Ovarian cancer (OC) is the most lethal among gynecologic malignancies worldwide. Unfortunately, in around 70% of cases cancer is diagnosed in late stages (III-IV) which decreases the 5-year survival rate to 25%. The standard of care in ovarian cancer is debulking surgery followed by chemotherapy regimens based on platinum salts. Since 2014 PARP inhibitors became available for OC patients with germline or/and somatic mutations in BRCA1/2, including maintenance therapy. BRCA1/2 Next Generation Sequencing (NGS)-based analysis of formalin-fixed paraffin-embedded (FFPE) ovarian cancer samples becomes the standard of care. The aim of the present study was to evaluate the frequency of mutations in 201 unselected ovarian cancer tissues using the NGS method. In total, pathogenic mutations in both genes were detected in 24% (49/201) of the ovarian cancer cases tested. For 41 patients the results of testing of DNA isolated from blood sample revealed that 17% (35/201) mutations were germline origin, whereas 3% (6/201) mutations were somatic. In 4% (8/201) cases blood sample was inaccessible. The presence of pathogenic mutations was correlated with younger age at diagnosis and serous subtype. Close cooperation between many specialists (gynecologist, pathologist, oncologist, clinical genetics and molecular biologist) is indispensable for efficient and on-time BRCA1/2 ovarian tumor tissue testing.

Ketogenic diet and cardiovascular risk - state of the art review.

The ketogenic diet is based on extreme carbohydrate intake reduction and replacing the remaining with fat and has become a popular dietary pattern used for weight loss. The relationship between the ketogenic diet and cardiovascular risk is a controversial topic. This publication aimed to present evidence on the ketogenic diet and cardiovascular risk factors and mortality. The ketogenic diet does not fulfill the criteria of a healthy diet. It presents the potential for rapid short-term reduction of body mass, triglycerides level, Hb1Ac, and blood pressure. Its efficacy for weight loss and the above-mentioned metabolic changes is not significant in long-term observations. In terms of cardiovascular mortality, the low-carb pattern is more beneficial than very low-carbohydrate (including the ketogenic diet). There is still scarce evidence comparing ketogenic to the Mediterranean diet. Other safety concerns in cardiovascular patients such as adverse events related to ketosis, fat-free mass loss, or potential pharmacological interactions should be also taken into consideration in future research.

Dietary strategies for cardiovascular disease risk factors prevention.

Nutrition can play a key role in cardiovascular disease risk reduction, and its risk factors modification. This paper aims to present, compare, and summarize the main dietary concepts for preventing the main cardiovascular disease risk factors - obesity, hypertension, and dyslipidemia. The dietary models and macronutrient intakes were compared between main cardiovascular risk factors prevention recommendations. Dietary recommendations related to selected cardiovascular risk factors share the points, that can be suggested as crucial for overall cardiovascular risk factors reduction. Recommendations suggest limiting saturated fatty acids intake to <10% of total caloric intake in obesity, and <7 % in hypercholesterolemia, along with an increased intake of mono- and polyunsaturated fatty acids. In addition, daily dietary fiber intake should reach a level of 25-40 g. The vegetables and fruits should be consumed at a daily minimum level of 200g (or 4-5 portions) each. Salt intake should not exceed 5g/day. Alcohol should be generally avoided, and moderate intake levels (sex-specific) should not be exceeded. It is also worth noting, that proteins are essential for tissue formation and regeneration. Carbohydrates are the main source of energy, but it is necessary to choose products with a low glycemic index. Dietary antioxidants help combat free radicals and prevent cell damage.

Nutritional Status Predicts the Length of Stay and Mortality in Patients Undergoing Electrotherapy Procedures.

(1) Background: Nutritional status is a factor that impacts the patients' outcomes in various medical conditions including cardiovascular patients or surgical procedures. However, there is limited available information about its impact on the short-term outcomes of cardiac implantable electronic device (CIED) implantations. This study aimed to assess the relationship between nutritional status, complications, mortality risk, and length of stay at the hospital in patients undergoing CIED implantations. (2) Material and Methods: 588 patients who underwent CIED implantation in 2022 and 2023 were included in the retrospective analysis. The nutritional status assessment was performed using NRS 2002 and BMI. The implanted devices were single-chamber pacemakers (n = 82), dual-chamber pacemakers (n = 329), one-chamber ICDs (n = 83), dual-chamber ICDs (n = 19), CRT-P (n = 19), and CRT-D (n = 56). (3) Results: The regression analysis showed that the NRS 2002 score predicted the length of stay (age-adjusted: ß = 1.02, p = 0.001) among the CIED-implanted patients. The CRT-D subgroup was particularly responsible for this relationship (ß = 4.05, p = 0.003 after age adjustment). The analysis also revealed significant differences between the NRS 2002 score in the in-hospital death subgroups (1.75 ± 1.00 points for deaths vs. 1.00 ± 1.00 points for survivors; p = 0.04). There were no significant differences in nutritional status parameters regarding early complications subgroups. (4) Conclusions: This study showed that nutritional risk assessed with NRS 2002 is a predictor of length of stay (particularly for CRT-D) and mortality among patients undergoing CIED implantations. The results of the analysis point out the impact of patients' nutritional status on short-term outcomes of CIED implantations, particularly in CRT-D implants where 1 NRS 2002 point was a predictor of a mean 4.05 days (77.2%) longer hospitalization.

The Impact of Education Level on Individual Lifestyle Behaviors among Dietetics Students and Professionals.

Lifestyle and habits are acquired in the family environment and then shaped by the potential influence of the environment and received education. In recent years, there has been growing interest in understanding the relationship between sleep and dietary behaviors in various health professionals, including medical and dietetics professionals and students, as well as their self-perceived knowledge and attitudes. Despite the importance of this topic, there is a lack of research on the assessment of individual behaviors in dietetics students and professionals. The aim of this study was to assess the impact of education level on individual behaviors regarding nutrition, sleep, and physical activity in dietetics students and professionals. 71 dietetics students and professionals were enrolled in this study. Their overall knowledge, sleep, and nutritional behavior were assessed with a validated Questionnaire of Eating Behaviors at the beginning of their dietetics university education and then prospectively after a year. It was also compared to dieticians who already graduated. The analysis showed that the educational level did not correlate with sleep length or the physical activity level. However, the educational level was correlated with dietary knowledge and properly self-assessed by the participants. Significant differences were observed in both the prospective and comparative analyses. The educational level and knowledge were not correlated with eating behaviors. The self-assessment of nutritional behaviors also did not correlate with the objective assessment. Sleep length did not correlate with BMI, but it was inversely correlated with overall and healthy diet scores and knowledge levels. On the other hand, physical activity levels were positively correlated with healthy diet scores. Dietary education results in better nutritional knowledge; however, it does not significantly impact individual nutritional behaviors among dietetics students and professionals. Moreover, the inverse relationship between sleep length and nutritional knowledge and behaviors, as well as the positive relationship between physical activity level and dietary behaviors, shows that nutritional aspects of lifestyle are probably prioritized among dietetic students and professionals, with an acknowledgment of the role of physical activity and a neglect of sleep hygiene importance. Dietetics students should be advised to use their theoretical knowledge not only to guide their patients but also to implement it in their own lives.

The Relationship between Dietary Flavonols Intake and Metabolic Syndrome in Polish Adults.

Metabolic syndrome (MetS) is a cluster of metabolic disorders primarily caused by central obesity, which results in chronic inflammation leading to hypertension, diabetes and atherogenic dyslipidemia. Inflammation underlying MetS could be the target for dietary flavonols as they present antioxidative properties. The aim of this paper was to analyze the differences in habitual intake of selected flavonols (quercetin, kaempferol, isorhamnetin and myricetin) between MetS patients and healthy participants, and its relationship with MetS advancement. Ninety participants were enrolled in this study. The one-year flavonol intake was assessed with a dedicated food frequency questionnaire. The patients with MetS consumed significantly less quercetin (p = 0.01), kaempferol (p = 0.04), isorhamnetin (p < 0.001), total flavonols (p = 0.01), tomatoes (p = 0.001) and wine (p = 0.01) daily. Further analysis revealed a moderate inverse correlation between quercetin (p = 0.001), kaempferol (p = 0.01), isorhamnetin (p < 0.001), total flavonols (p = 0.001) and tomato consumption (p = 0.004) and MetS stage. The analysis of laboratory parameters showed that dietary intake of flavonols was not correlated with lipid profile, glucose level or renal function. On the basis of this observation, a potential protective effect of dietary flavonols, mainly from tomatoes, against MetS could be suggested. However, when referring to MetS components, flavonols probably mainly impact central obesity and blood pressure, without a significant impact on conventional lipid-profile parameters and glucose level.

Nutritional Status of Coronary Artery Disease Patients-Preliminary Results.

INTRODUCTION: Malnutrition is a condition that negatively impacts the clinical outcomes of numerous diseases. The aim of this study was to assess the nutritional status of coronary artery disease (CAD) patients and to investigate its relationship with the main clinical aspects of CAD. MATERIAL AND METHODS: 50 CAD patients undergoing coronary angiography were enrolled in this study. The nutritional status assessment was based on Nutritional Risk Score 2002 (NRS 2002), body mass index (BMI), and bioelectrical impedance analysis (BIA) measurements. RESULTS: The analysis showed a moderate inverse correlation between NRS 2002 and BIA phase angle measured at 50 kHz (R: -0.31; p = 0.03) and Z200/5 parameter (R: 0.34; p = 0.02). The analysis of CAD clinical parameters showed a significant correlation between NRS 2002 and Canadian Cardiovascular Society (CCS) class (R: 0.37; p = 0.01). Left ventricle ejection fraction (LVEF) was correlated with BMI (R: 0.38; p = 0.02), however further BIA revealed hydration changes as LVEF was correlated to intracellular (ICF) and extracellular fluid (ECF) proportion: positively with ICF (R: 0.38; p = 0.02) and negatively with ECF (R: -0.39; p = 0.02). CONCLUSIONS: NRS 2002 and BIA are valuable tools for nutritional status assessment in CAD patients. Malnutrition is related to the severity of CAD symptoms, particularly in women. Maintaining proper nutritional status can have a potentially important role in this group of patients.

Bioelectrical Impedance Analysis and Body Composition in Cardiovascular Diseases.

Nutritional status and body composition in cardiovascular (CV) patients are important aspects of their performance. Bioelectrical impedance analysis (BIA) is a noninvasive method that provides reliable information about bioelectrical parameters which reflect nutritional status and body composition data. The aim of this paper was to describe BIA, its advantages, limitations, and clinical applications in CV patients. The PubMed database was searched for all papers showing the use of BIA in CV conditions until January 1, 2023. A total of 42 papers regarding BIA application in CV patients were identified. Phase angle, Z200/5 parameter, and membrane capacitance are the BIA parameters that can be used for nutritional status assessment in CV patients, mainly in heart failure and after myocardial infarction. Among secondary body composition parameters, fat mass can be used for obesity assessment which is a CV risk factor. Body cell mass can be used together which the direct BIA parameters for nutritional status assessment which is an important factor in treatment outcome, quality of life, and disease prognosis. Total body water can be used for hydration assessment in heart failure and during invasive procedures. To conclude, BIA is a noninvasive method that provides essential information about the general condition of the body which is the result of nutritional and hydration status in CV patients.

Apple Peel Supplementation Potential in Metabolic Syndrome Prevention.

(1) Introduction: Apples are a source of bioactive substances, e.g., anthocyanidins and flavonols, and dietary fiber. Their highest concentrations are observed in the skin. Metabolic syndrome (MetS) is a set of conditions originally associated with obesity. Excessive adipose tissue accompanying obesity leads to chronic inflammation and metabolic disorders, which result in the development of dyslipidemia, elevated blood pressure, and glucose levels. Thus, supplementation of apple peels, a source of antioxidant substances and fiber, could potentially be a method supporting the prevention of MetS. This paper summarizes the results of available research on the potential impact of apple peel supplementation on the components of MetS. (2) Results: The results from in vitro and animal model studies indicate a positive effect of apple peel supplementation on lipid profile, glucose levels, and blood pressure regulation mediators. Only one human study was performed, and it showed that the consumption of apple peels had an effect on endothelial function but not on other clinical parameters. At the moment, there are no results from observations on large groups of people available. (3) Conclusions: The results of in vitro and animal-model studies indicate the potential of apple peel supplementation in MetS prevention, but it has not been clinically confirmed in human studies. Conducting large human studies could allow a definite clarification of the role of apple peel supplementation in MetS prevention.

The Relationship between Knowledge, Dietary Supplementation, and Sleep Quality in Young Adults after the COVID-19 Pandemic.

INTRODUCTION: Sleep is one of the most important factors affecting the quality of life. More than 50% of Polish adults have sleeping disorders, and young adults are the ones particularly vulnerable to this. This is why the analysis of the predictors of sleep quality, such as sleep hygiene knowledge and dietary knowledge, in young adults is a very important topic, especially after the COVID-19 pandemic, which may have affected sleeping habits. MATERIAL AND METHODS: 402 young adults (mean age 28.12 ± 6.08 years old) were enrolled in the study during the COVID-19 pandemic. Sleep quality was assessed with the Pittsburgh Sleep Quality Questionnaire, while dietary knowledge and sleep hygiene knowledge were assessed with dedicated questionnaires. The participants were also asked about the use of specific dietary supplements. RESULTS: The analysis showed that sleep hygiene knowledge was significantly associated with sleep length (R = -0.17, p = 0.003) and overall sleep quality (R = -0.17, p = 0.005), while dietary knowledge significantly correlated with time to fall asleep (R = -0.12, p = 0.026). The regression analysis revealed that sleep hygiene knowledge was a significant negative predictor of sleep quality impairment (ß = -0.13, p = 0.028). Significant results were also obtained for the use of supplements (ß = -0.20; p = 0.001) and the use of medications (ß = -0.32, p = 0.001), which were negative predictors of sleep quality impairment. CONCLUSIONS: This study showed that increased sleep hygiene knowledge promoted improved sleep length and overall sleep quality. In addition, dietary knowledge significantly correlated with time to fall asleep. On the other hand, decreased sleep quality was observed in participants who used medications or dietary supplements.

The Impact of Dietary Flavonols on Central Obesity Parameters in Polish Adults.

Background: Central obesity is defined as the excessive fat tissue located in abdominal region accompanied by systemic inflammation, which drives to cardiovascular disease. Flavonols are antioxidative agents present in food. The aim of this study was investigating the relationship between dietary flavonols intake and central obesity. Methods and results: 80 participants (40 central obese and 40 healthy controls) were administered a food frequency questionnaire dedicated to flavonols intake assessment. Body composition was measured with bioelectrical impedance analysis. The analysis showed significant differences between central obese participants and healthy controls in total flavonol (p = 0.005), quercetin (p = 0.003), kaempferol (p = 0.04) and isorhamnetin (p < 0.001) habitual intake. Among central obese participants, there was a moderate inverse correlation between fat mass (FM) and total flavonol (R = −0.378; 95% CI: −0.620 to −0.071; p = 0.02), quercetin (R = −0.352; 95% CI: −0.601 to −0.041; p = 0.03), kaempferol (R = −0.425; 95% CI: −0.653 to −0.127; p = 0.01) and myricetin intake (R = −0.352; 95% CI: −0.601 to −0.041; p = 0.03). BMI was inversely correlated with total flavonol (R = −0.330; 95% CI: −0.584 to −0.016; p = 0.04) and quercetin intake (R = −0.336; 95% CI: −0.589 to −0.023; p = 0.04). Waist circumference was inversely correlated with total flavonol (R = −0.328; 95% CI: −0.586 to −0.009; p = 0.04), quercetin (R = −0.322; 95% CI: −0.582 to −0.002; p = 0.048) and myricetin intake (R = −0.367; 95% CI: −0.615 to −0.054; p = 0.02). Among flavonols' dietary sources, there was an inverse correlation between black tea consumption and FM (R: −0.511; 95% CI: −0.712 to −0.233; p < 0.001) and between coffee and waist circumference (R: −0.352; 95% CI: −0.604 to −0.036; p = 0.03) in central obese participants. Conclusions: The higher flavonol intake could play a protective role in abdominal obesity development. What is more, total and selected flavonol dietary intakes are inversely correlated with the parameters used for obesity assessment in central obese participants. The habitual consumption of products rich in flavonols, mainly tea and coffee, could possibly have a preventive role in abdominal obesity development.

The Impact of Flavonols on Cardiovascular Risk.

Cardiovascular disease (CVD) is the leading cause of deaths globally. The main target for prevention of cardiovascular (CV) risk are lifestyle changes, including particular dietary recommendations, involving high intake of fruits and vegetables. Flavonols are a subgroup of flavonoids-compounds present in fruits, vegetables, and tea-known for their antioxidative properties. There are many findings about the beneficial impact of flavonols on general CV risk and its factors, but mainly from in vitro and animal model studies. This paper summarizes data from human studies about flavonols' impact on general CV risk and its factors. A high dietary intake of flavonols could decrease CVD mortality directly or through impact on selected CV factors; however, available data are inconsistent. Nonetheless, specific groups of patients (smoking men, hypertensive and diabetic patients) can potentially benefit from selected dietary modifications or flavonols (quercetin) supplementation. Future investigations about kaempferol and myricetin are needed.

Dietary Isorhamnetin Intake Is Inversely Associated with Coronary Artery Disease Occurrence in Polish Adults.

The role of antioxidative agents in coronary artery disease (CAD) has been investigated, but the analysis of specific flavonols intake in Polish adults requires validated tools. The aim of this study was to estimate the dietary intake of flavonols in CAD patients by creating a food frequency questionnaire (FFQ) dedicated for this purpose in Polish adults. The FFQ included 140 products from 12 food groups. The study involved 103 adult respondents (43 CAD patients and 60 healthy controls). Mean daily intakes of total flavonols, quercetin, kaempferol, myricetin and isorhamnetin were calculated as absolute values and quartiles. Mean daily intakes of 12 main food categories and 27 subcategories were calculated as portions and quartiles. The validity test revealed high correlation for total flavonols, kaempferol, myricetin and isorhamnetin and moderate for quercetin. In the reproducibility analysis, the correlation was high for total flavonols, quercetin, kaempferol and myricetin, moderate for isorhamnetin and high for all 12 categories and 25 out of 27 subcategories of the tested food groups. The application of the FFQ in healthy adults and CAD patients revealed that dietary intakes of total flavonols and proportional intakes of kaempferol and isorhamnetin in Polish adults and CAD patients are higher than in most other European countries, while the proportional intakes of quercetin and myricetin are lower than in most European countries. The comparison between CAD patients and the healthy controls revealed significant differences in dietary isorhamnetin intake (p = 0.002). The results suggest that dietary isorhamnetin could have a potential role in CAD prevention.

Cardiac Resynchronization Therapy Remote Monitoring - COVID-19 Pandemic Experiences and Future Perspectives.

Cardiac resynchronization therapy (CRT) is a well-established form of the treatment for heart failure (HF) in patients with left ventricle contraction dyssynchrony. Apart from typical in-office management, remote monitoring enables constant surveillance on both the patient's and the device's condition. This way, in case of any problems, clinical decisions could be made earlier leading to better outcome of CRT patients. COVID-19 pandemic with following lockdowns in many countries resulted in getting more attention on remote monitoring systems. The aim of this paper was to gather and summarize worldwide experiences from CRT remote monitoring during COVID-19 pandemic and point out future possibilities for HF patients treated with CRT. Already published experiences from remote monitoring of CRT devices during COVID-19 restrictions confirmed previous advantages of telemedical approach, however, more publications in this area would be helpful.

The Effects of Quercetin Supplementation on Blood Pressure - Meta-Analysis.

The effects of quercetin supplementation on blood pressure (BP) remain unclear. The aim of this meta-analysis is to summarize data focused on quercetin impact on systolic BP (SBP) and diastolic BP (DBP). Medline, EMBASE and Web of Science databases were searched to identify randomized controlled trials that assessed the impact of quercetin on BP until May 2022. A random-effects model was used for data analysis. Subgroup analysis was performed to explore the effects in (pre)hypertensive and normotensive adults. Ten trials (841 participants in total) were included into the analysis. The results showed that quercetin supplementation significantly decreased SBP in the mixed population (MD: -2.38mmHg; 95% CI: -3.80 - -0.96; P = 0.01) and in the normotensive subgroup (MD: -1.82mmHg; 95% CI: -2.43 - -1.20; P < 0.0001) and DBP in the (pre)hypertensive subgroup (MD: -3.14mmHg; 95% CI: -4.44 - -1.84; P < 0.00001). Quercetin supplementation decreases BP in normotensive and (pre)hypertensive patients.

Dietary Isorhamnetin Intake Is Associated with Lower Blood Pressure in Coronary Artery Disease Patients.

Background: Recent studies suggest the positive role of flavonols on blood pressure (BP) values, although there are not many conducted on humans. The aim of this study was to examine the relationship between flavonol intake and their main sources of consumption, and systolic (SBP) and diastolic (DBP) BP values in coronary artery disease (CAD) patients. Methods and results: forty CAD patients completed a food-frequency questionnaire dedicated to flavonol-intake assessment. The analysis revealed significant correlation between isorhamnetin intake and SBP values­absolute (R: −0.36; 95% CI: −0.602 to −0.052; p = 0.02), and related to body mass (R: −0.38; 95% CI: −0.617 to −0.076; p = 0.02. This effect was observed in male participants (R: −0.65; 95% CI: −0.844 to −0.302; p = 0.001 and R: −0.63; 95% CI: −0.837 to −0.280; p = 0.002 respectively), but not in female patients. The main contributors were onions, tomatoes, blueberries, apples, tea, coffee and wine. White onion (R: −0.39; 95% CI: −0.624 to −0.088; p = 0.01) consumption was inversely correlated with SBP, and tomato consumption (R: −0.33; 95% CI: −0.581 to −0.020; p = 0.04) with DBP. The comparison between patients with BP < 140 mmHg and ≥140 mmHg revealed significant differences in white onion (p = 0.01) and blueberry (p = 0.04) intake. Conclusions: This study revealed the relationship between long-term dietary isorhamnetin intake and SBP values. The analysis of specific food intake showed that onion, tomato and blueberry consumption could impact BP values. This may suggest that a dietary approach which includes a higher intake of isorhamnetin-rich products could possibly result in BP lowering in CAD patients.

Potential bioelectrical impedance analysis (BIA) parameters in prediction muscle strength in women with anorexia nervosa.

OBJECTIVES: The role of physical activity in anorexia nervosa (AN) treatment has been investigated. Muscle strength (MS) reflects physical condition and can predict AN patients' response to this novel treatment approach. This study was intended to find bioelectrical impedance analysis (BIA) parameters that predict AN patients' MS. METHODS: The study included 42 AN patients and 42 healthy ones in the control group. BIA parameters that predict MS were assessed by dividing AN patients into groups by their hand grip strength test score (higher/lower than 22.5 kg). RESULTS: The highest accuracy for distinguishing AN subjects from the control group was achieved by cell membrane capacitance (AUC = 0.916), impedance at 200 kHz and 5 kHz ratio (AUC = 0.924), phase angle (PA) 5 kHz (AUC = 0.906) and PA 50 kHz (AUC = 0.919). The low MS group had significantly lower values of PA 50 kHz (mean: 4.03 ± 0.80° vs. 4.58 ± 0.65°; p = 0.032) and fat-free mass index (mean: 12.22 ± 1.41 kg/m2 vs. 13.14 ± 0.94 kg/m2; p = 0.026). In the univariate model, PA 50 kHz ≥4.037° was associated with the lowest chance of muscle weakness (OR = 0.230; p = 0.005). In the multivariate analysis, PA 50 kHz was the only significant factor of MS (OR = 0.01; p = 0.027). CONCLUSIONS: PA 50 kHz is the best BIA parameter to predict MS in AN patients. It could be useful for assessment before physical activity treatment application.

Cell-free DNA BRAF V600E measurements during BRAF inhibitor therapy of metastatic melanoma: long-term analysis.

OBJECTIVE: We assessed the status of the BRAF V600E mutation in cell-free circulating tumor DNA (cfDNA) isolated from the plasma of patients with metastatic melanoma treated with the BRAF inhibitor vemurafenib, collected at different time points during therapy to evaluate the sensitivity and specificity of quantitative polymerase chain reaction and droplet digital polymerase chain reaction (ddPCR) and the correlation between the level of plasma cfDNA p.V600E and the long-term clinical outcome. METHODS: cfDNA in patients with BRAF-mutated melanoma (n = 62) was analyzed at baseline and at 4-8 weeks from the start of vemurafenib therapy. BRAF mutations were assessed using tumor tissue-derived DNA and circulating cfDNA from plasma samples. Quantification of BRAF V600E was performed in cfDNA using ddPCR. RESULTS: cfDNA V600E was detected in the plasma of 48/62 (77%) patients at baseline and in 18/62 (29%) patients after 4-8 weeks of treatment. Patients positive for BRAF mutations in cfDNA at baseline had shorter progression-free survival (PFS) and overall survival (OS) compared with patients with undetectable cfDNA BRAF mutations. Undetectable cfDNA p.V600E at baseline and after 4-8 weeks of therapy was associated with the best prognosis. When treated as a continuous variable, the log-transformed concentration of baseline cfDNA p.V600E was significantly associated with both PFS and OS. This effect was retained in the multivariate OS Cox model adjusted for Eastern Cooperative Oncology Group performance status, the presence of brain metastases, patient age, and previous systemic treatment. CONCLUSIONS: Monitoring of plasma BRAF p.V600E cfDNA concentrations in patients with metastatic melanoma on targeted therapy may have prognostic value. Undetectable cfDNA p.V600E before and during treatment was associated with a favorable prognosis.

BRCA1 founder mutations and beyond in the Polish population: A single-institution BRCA1/2 next-generation sequencing study.

Hereditary mutations in BRCA1/2 genes increase the risk of breast cancer by 60-80% and ovarian cancer by about 20-40% in female carriers. Detection of inherited mutations in asymptomatic carriers allows for the implementation of appropriate preventive measures. BRCA1/2 genotyping is also important for poly(adenosine diphosphate)-ribose polymerase (PARP) inhibitor administration. This work addresses the need for next-generation sequencing (NGS) technology for the detection of BRCA1/2 mutations in Poland where until recently mostly founder mutations have been tested, and whether BRCA diagnostics should be extended beyond the panel of founder mutations in this population. The study comprises 2931 patients who were referred for genetic counseling and tested for founder and recurrent mutations in BRCA1 (5382insC (c.5266dupC; p.Gln1756Profs), c.5370C>T (c.5251C>T; p.R1751*), 300T>G (c.181T>G; p.Cys61Gly), 185delAG (c.68_69delAG; p.Glu23Valfs), and 4153delA (c.4035delA; p.Glu1346Lysfs)) by high-resolution melting/Sanger sequencing. A total of 103 (3.5%) mutations were detected, including 53 (51%) in healthy subjects and 50 (49%) in cancer patients. Then, based on more stringent clinical and pedigree criteria, sequencing of all BRCA1/2 exons was performed in 454 (16%) patients without founder mutations by NGS, which detected 58 mutations (12.8%), 40 (8.8%) of which were pathogenic. In 14 (3.1%) subjects, variants of uncertain significance (VUS) were detected, and in four (0.9%) subjects, the detected mutations were benign. In total, 161 mutations were detected using our two-step algorithm (founder test and NGS), of which 64% were founder mutations, 25% were NGS-detected pathogenic mutations, 9% were VUS, and 2% were benign. In addition, 38 mutations not yet reported in the Polish population were detected. In total, founder mutations accounted for only 64% of all detected mutations, and the remaining mutations (36%) were dispersed across the BRCA1/2 gene sequences. Thus, in Poland, testing for constitutional mutations in BRCA1/2 should be carried out in two stages, where NGS is performed in qualifying subjects if founder mutations are not identified.