Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with CHEK2 Germline Mutations.

The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2.

Tumor location matters, next generation sequencing mutation profiling of left-sided, rectal, and right-sided colorectal tumors in 552 patients.

Despite the introduction of new molecular classifications, advanced colorectal cancer (CRC) is treated with chemotherapy supplemented with anti-EGFR and anti-VEGF targeted therapy. In this study, 552 CRC cases with different primary tumor locations (250 left side, 190 rectum, and 112 right side) were retrospectively analyzed by next generation sequencing for mutations in 50 genes. The most frequently mutated genes were TP53 in left-sided tumors compared to right-sided tumors and BRAF in right-sided tumors compared to left-sided tumors. Mutations in KRAS, NRAS, and BRAF were not detected in 45% of patients with left-sided tumors and in 28.6% of patients with right-sided tumors. Liver metastases were more common in patients with left-sided tumors. Tumors on the right side were larger at diagnosis and had a higher grade (G3) than tumors on the left. Rectal tumors exhibit distinctive biological characteristics when compared to left-sided tumors, including a higher absence rate of KRAS, NRAS, and BRAF mutations (47.4% in rectal versus 42.8% in left-sided tumors). These rectal tumors are also unique in their primary metastasis site, which is predominantly the lungs, and they have varying mutation rates, particularly in genes such as BRAF, FBXW7, and TP53, that distinguish them from tumors found in other locations. Primary tumor location has implications for the potential treatment of CRC with anti-EGFR therapy.

Agreement between Accelerometer-Assessed and Self-Reported Physical Activity and Sedentary Behavior in Female Breast Cancer Survivors.

An accurate quantitative assessment of physical activity and sedentary lifestyles enables a better understanding of their relationship with the health records of cancer survivors. The objective of this study was to compare the subjective and objective methods of physical activity measurement in female breast cancer survivors. Materials and methods: In total, 135 female breast cancer survivors at the Holycross Cancer Center, Kielce, Poland, were included in this study. A shortened version of the International Physical Activity Questionnaire (IPAQ) was used to subjectively assess the participants' physical activity (PA), and an ActiGraph GT3X-BT accelerometer was used for an objective assessment. In total, 75% of the studied women did not report any vigorous PA, irrespective of the measurement method. The average values of moderate PA and moderate-to-vigorous PA (MVPA) measured with IPAQ compared with the accelerometer were sevenfold and tenfold higher, respectively. Conversely, the sedentary behavior values measured with the accelerometer were almost three times higher than those measured with IPAQ. The PA and sedentary behavior measurements were significantly different. Irrespective of PA intensity, the accelerometer-based measurements produced significantly lower results than IPAQ, while higher results were observed for sedentary behavior. The measurement differences between these two methods increased as the average differences grew. Regardless of the measurement method, a negative association was observed between moderate PA with general adiposity and adipose tissue distribution, whereas sedentary behavior demonstrated an opposite trend. This indicates the detrimental role of obesity in limiting PA.

Next-Generation Sequencing-Based Analysis of Clinical and Pathological Features of PIK3CA-Mutated Breast Cancer.

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients.

Research into the Association of Cadmium and Manganese Excretion with Thyroid Function and Behavioral Areas in Adolescents with Autism Spectrum Disorders.

Thyroid dysfunction and toxic metal exposure have been linked to the increased risk of autism spectrum disorders (ASD); however, the relationship between those factors remains unclear. We aimed to evaluate the relationship between the serum level of hormones, namely thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and urinary cadmium (U-Cd) and urinary manganese (U-Mn), in patients with ASD. The study group consisted of 129 adolescents with ASD, and the control group consisted of 86 healthy persons. Ion chromatography with spectrophotometric detection (IC-UV/ViS) was used to quantitatively determine Cd and Mn in all 24-h urine samples. These results indicate that severity of certain symptoms in autism is associated with thyroid function. Correlation analysis between Childhood Autism Rating Scale (CARS) results and the content of both U-Mn and U-Cd as well as fT3, fT4 and TSH values in ASD patients showed significantly positive correlation of CARS7 (visual reaction) with fT3 and fT4 and a negative correlation with TSH for the whole study group. In the group of adolescents over 14 years of age, it was also observed that CARS10 (anxiety reaction) negatively correlates with serum TSH levels, and among younger individuals, CARS9 (near receptor responsiveness, taste, smell) positively correlates with TSH.

Is ERCC1 a prognostic biomarker for urothelial cancer following radical cystectomy? A long-term analysis.

INTRODUCTION: Excision repair cross-complementation 1 protein (ERCC1) plays a vital role in cancer cells enabling DNA repair via nucleotide excision repair. Thus, we hypothesized whether expression of this protein may be utilized as a prognostic marker in patients after radical cystectomy. MATERIAL AND METHODS: The final analysis involved 123 patients with urothelial bladder carcinoma who underwent radical cystectomy with bilateral lymphadenectomy. The median follow-up time was equal to 853 days. ERCC1 status was evaluated immunohistochemically with the application of tissue microarrays. RESULTS: Positive ERCC1 expression was noted in 46% of the studied cases. Among the analyzed clinical and pathological factors, we could not establish a statistically significant correlation with ERCC1. Similarly, survival curves were statistically indifferent in patients with tumors categorized according to both expression categories. We did not confirm a prognostic value of ERCC1 in the multivariate regression analysis. CONCLUSIONS: ERCC1 expression does not influence the overall survival of patients with urothelial bladder carcinoma after radical cystectomy.

Two-year follow-up cohort study focused on gender-specific associations between socioeconomic status and body weight changes in overweight and obese middle-aged and older adults.

OBJECTIVE: As overall spread of obesity in populations is generally acknowledged to result from unhealthy lifestyles rather than individual genetic makeup, this study aimed to gain specific insights into its determinants through assessing the prevalent associations between individual socioeconomic status (SES) and weight loss in overweight and obese men and women. METHODS: A prospective, 2-year follow-up study covered 3362 (38.0% men) respondents, aged 43-64 years, body mass index ≥25 kg/m2. Changes in body weight were estimated as a percentage of initial weight. Three categories of changes were defined: gained ≥3%, stable (gained <3% or lost <3%), lost ≥3%. Body weight loss was determined against three categories: lost ≥3 to <5%, lost ≥5 to <10%, lost ≥10%. Select SES variables (ie, gender, age, education, marital status, occupational activity and income) were determined in line with the Health Status Questionnaire. The associations between SES and body weight changes were analysed with the aid of logistic regression models. The results were presented as ORs with 95% CIs. RESULTS: Only 18% of the respondents had complied with the medical recommendations on weight loss. Significant differences were encountered between the gender, age and occupational activity variables and the weight loss one. Multifactorial models were used to determine the following gender-specific associations between SES and weight loss. Men with moderate income had significantly higher odds for weight loss (≈75%), as compared with the higher earners, whereas women with low income, occupationally inactive, had significantly higher odds (≈30% and ≈50%, respectively), as compared with the high earners and occupationally active ones. CONCLUSIONS: Lower education, male gender, lower income per household, older age and unemployment status were the established factors predisposing to obesity. While aiming to ensure effectiveness of the measures specifically aimed at preventing obesity, population groups deemed most at risk of potential weight gain must prior be identified.

Evaluation of Complete Pathological Regression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients with BRCA1 Founder Mutation Aided Bayesian A/B Testing Approach.

The aim of this study was to evaluate the probability of pathologic complete regression (pCR) by the BRCA1 gene mutation status in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy. The study involved 143 women (mean age 55.4 ± 13.1 years) with TNBC. The BRCA1 mutation was observed in 17% of the subjects. The most commonly used (85.3%) chemotherapy regimen was four cycles of adriamycine and cyclophosphamide followed by 12 cycles of paclitaxel (4AC + 12T). The differences between clinico-pathological factors by BRCA1 status were estimated. Odds ratios and 95% confidence intervals for pCR vs. non-pCR were calculated using logistic regression. The probability distribution of pCR based on BRCA1 status was estimated using beta distributions. The presence of T3-T4 tumours, cancer in stages II and III, lymphovascular invasion, and the use of chemotherapy schedules other than 4AC + 12T significantly decreased the odds of pCR. It was established that there was a 20% chance that pCR in patients with the BRCA1 mutation was 50% or more times as frequent than in patients without the mutation. Thus, the BRCA1 mutation can be a predictive factor for pCR in patients with TNBC.

Competing Risks of Cancer and Non-Cancer Mortality When Accompanied by Lifestyle-Related Factors-A Prospective Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: The study aimed to identify the association between the lifestyle-related factors and the cancer-specific, or non-cancer-specific mortality, when accompanied by a competing risk. Two statistical methods were applied, i.e., cause-specific hazard (CSH), and sub-distribution hazard ratio (SHR). Their respective key advantages, relative to the actual study design, were addressed, as was overall application potential. METHODS: Source data from 4,584 residents (34.2% men), aged 45-64 years, were processed using two different families of regression models, i.e., CSH and SHR; principal focus upon the impact of lifestyle-related factors on the competing risk of cancer and non-cancer mortality. The results were presented as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: Age, smoking status, and family history of cancer were found the leading risk factors for cancer death; the risk of non-cancer death higher in the elderly, and smoking individuals. Non-cancer mortality was strongly associated with obesity and hypertension. Moderate to vigorous physical activity decreased the risk of death caused by cancer and non-cancer causes. CONCLUSIONS: Specific, lifestyle-related factors, instrumental in increasing overall, and cancer-specific mortality, are modifiable through health-promoting, individually pursued physical activities. Regular monitoring of such health-awareness boosting pursuits seems viable in terms of public health policy making.

Assessment of Age-Induced Changes in Body Fat Percentage and BMI Aided by Bayesian Modelling: A Cross-Sectional Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: Loss of fat-free mass (FFM) and gain in body fat (BF) are the key disability risk factors, also instrumental in perpetuating already existing functional disorders. Obesity construed in terms of body mass index (BMI) values, in view of undesirable gain in BF, is a risk factor for cardio-metabolic disorders. Both detrimental processes clearly evidence a scope of involutionary changes characteristic of an aging population, also standing for one of its greatest burdens. PURPOSE: The present study aimed to assess the changes in body composition (BC), in conjunction with the relationship between BF% and BMI, for defining overweight and obesity status in middle-aged and older adults, against the select indicator variables under study. MATERIALS AND METHODS: The study involved 4799 individuals (33.7% men), PONS Project participants, aged 43-64 years. BF% was measured with the aid of bioelectrical impedance analysis (BIA) method. Age-induced changes in BC were determined against BF%, fat mass (FM), FFM, BMI, fat mass index (FMI), and fat-free mass index (FFMI). The relationship between BF% and BMI was established with the aid of Bayesian regression models, adjusted for gender and age. RESULTS: In both genders, BF% increased with age at a similar annual rate. The reduction of FFM was noted mainly in men, which in conjunction with BF% gain ensured BMI stability. The increase in BF% in women with stable FFM affected an increase in BMI. Regardless of the BMI threshold, the anticipated (predicted) BF% increased with age in both genders. CONCLUSION: Monitoring of BC is of particular importance in older adults, in view of appreciably better characteristics of both the short- and long-term health predictors, as well as overall potential for developing specifically targeted, effective health interventions.

A Two-Year Follow-Up Cohort Study-Improved Clinical Control over CVD Risk Factors through Weight Loss in Middle-Aged and Older Adults.

Modest weight loss enhances clinical control over cardiovascular disease (CVD) risk factors in overweight and obese individuals. This study aimed to assess the associations between individual weight loss and predefined criteria for clinical improvement in blood pressure, lipid levels, and glycemia. A two-year follow-up study involved 3388 (37.9% men) aged 45-64 years, BMI ≥ 25 kg/m2. Changes in body weight were calculated as a percentage of baseline weight; outcome variables: systolic (SBP), diastolic (DBP) blood pressure, high-density (HDL-C) and low-density (LDL-C) lipoproteins, fasting blood glucose (FBG), and triglycerides (TG) were construed as the differences between baseline and outcome values. Clinically significant improvement was defined as SBP/DBP reduction by 5 mm/Hg, FBG-20 mg/dL, LDL-C-10 mg/dL, TG-40 mg/dL, and HDL-C increase by 5 mg/dL. Apart from LDL-C, a modest 5%-10% weight loss was associated with clinically significantly improved outcomes. The incident rate ratios and 95% confidence intervals for clinical improvement of SBP were: 1.27 (1.14-1.40), DBP/1.30 (1.12-1.50), HDL/1.54 (1.18-2.02), and TG/1.69 (1.32-2.17). In the higher category of weight loss, associations were still manifest, although the results proved diagnostically challenging (low number of cases). Even though modest weight loss does enhance clinical control over CVD risk factors, offering regular medical guidance to patients is postulated to further boos the anticipated outcomes.

Optimal cut-off values for anthropometric measures of obesity in screening for cardiometabolic disorders in adults.

Excessive accumulation of body fat (BF) promotes obesity, whilst posing a significant health hazard. There being no agreed, optimal quantifying methods, application of BF variable in clinical practice is not deemed an effective assessment option. The study, involving 4,735 patients (33.6% men), aged 45-64, aimed to identify optimal cut-off values for anthropometric indicators of obesity to evaluate cardiometabolic risk. A minimum P-value approach was applied to calculate the cut-offs for BF%. Threshold values for body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height (WHTR) ratio, facilitating optimal differentiation of cardiometabolic risk, were based on BF%, expressed as a binary classifier. The newly estimated cut-off values for predicting cardiometabolic risk, based on BMI, were lower than the referential obesity thresholds, whereas the threshold values of WC, WHR, and WHTR were higher. Apart from dyslipidemia, the odds of cardiometabolic disorders were higher, when the anthropometric indicators under study exceeded the cut-off points in both sexes. The proposed cut-offs proved instrumental in predicting cardiometabolic risk, whilst highlighting diagnostic and clinical potential of BF%, whereas BMI boasted the highest predictive potential. Cardiometabolic risk also proved significantly higher even in the overweight patients.

Changes in survival of colorectal cancer patients in Swietokrzyskie Province (Southern Poland) from the second half of the 1990s to the early 21st century - a population-based study.

INTRODUCTION AND OBJECTIVES: For years, the increase in cancer incidence and deaths has constituted a significant health and social problem. Variation in the burden in cancers in different regions of the world requires constant monitoring of the epidemiological situation in this regard. Assessing survival in cancer patients is a valuable source of information for patients and physicians alike, as well as for politicians who have a direct impact on the shaping of health policy and health systems. The aim of the present study was to assess the changes in the 5-year relative survival of colorectal cancer patients during 1995-2014. MATERIAL AND METHODS: The data of 8,970 patients with colorectal cancer in the years 1995-2014, 5,033 males and 3,937 females aged 67.5 ± 11.7 from Swietokrzyskie Cancer Registry were used. Cases were classified according to the topographical codes ICD-O-3: C18.0-C18.9, C19.9, C20.9, C21.0-C21.2, C21.8. The end of follow-up was fixed at 31 December 2014. Four five-year calendar periods were defined. In each calendar period, relative survival rates using the Ederer II method were estimated separately for males and females. RESULTS: In 2010-2014 (against 1995-1999), the absolute increase in the 5-year relative survival in males and females with colon cancer was the highest and reached 9.8 percentage point (p.p.) and 9.6 p.p., respectively. Patterns of survival for both colon and rectal cancer patients according to gender and age were very similar. CONCLUSIONS: In 1995-2014, an increase in the value of relative survival rates of males and females with colorectal cancer was observed. Systematic increase in funding in health care was a chance for reducing the burden of colorectal cancer by more widespread and equal access of effective early detection and cancer treatment.

Optimal Body Fat Percentage Cut-Off Values in Predicting the Obesity-Related Cardiovascular Risk Factors: A Cross-Sectional Cohort Study.

BACKGROUND: Reliable obesity assessment is essential in evaluating the risk of cardiovascular risk factors (CRFs). Non-availability of clearly defined cut-offs for body fat percentage (BF%), as well as a widespread application of surrogate measures for obesity assessment, may result in incorrect prediction of cardio-metabolic risk. PURPOSE: The study aimed to determine optimal cut-off points for BF%, with a view of predicting the CRFs related to obesity. PATIENTS AND METHODS: The study involved 4735 (33.6% of men) individuals, the Polish-Norwegian Study (PONS) participants, aged 45-64. BF% was measured with the aid of bioelectrical impedance analysis (BIA) method. The gender-specific cut-offs of BF% were found with respect to at least one CRF. A P-value approach, and receiver operating characteristic curve analyses were pursued for BF% cut-offs, which optimally differentiated normal from the risk groups. The associations between BF% and CRFs were determined by logistic regression models. RESULTS: The cut-offs for BF% were established as 25.8% for men and 37.1% for women. With the exception of dyslipidemia, in men and women whose BF% was above the cut-offs, the odds for developing CRFs ranged 2-4 times higher than those whose BF% was below the cut-offs. CONCLUSION: Controlling BF% below the thresholds indicating an increased health hazard may be instrumental in appreciably reducing overall exposure to developing cardio-metabolic risk.

Age-Dependent Disparities in the Prevalence of Single and Clustering Cardiovascular Risk Factors: A Cross-Sectional Cohort Study in Middle-Aged and Older Adults.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide; with age acknowledged as an independent cardiovascular risk factor (CRF) in adults. Appreciating the association between age and classic CRFs is believed to boost all potential benefits of prevention. PURPOSE: Assessment of the prevalence of single and clustered CRFs and their association with age. PATIENTS AND METHODS: The survey involved 4735 people (33.6% men) who were PONS project attendees aged 45-64. The study protocol comprised the Health Status Questionnaire, general medical examination, anthropometric measurements, and blood and urine sampling. The prevalence of single and clustered CRFs (hypertension, dyslipidemia, diabetes mellitus, and obesity) in the incrementally split age groups was calculated. The incidence rate of CRFs, against their absence, was determined by Poisson regression models with robust standard errors. RESULTS: The prevalence of CRFs was established in 90% of the respondents. Except dyslipidemia and ≥1 CRFs, prevalence of risk factors increased with age, although this trend was the weakest in men. In the total group, and in women, prevalence of dyslipidemia and ≥1 CRFs was unrelated to age, whereas in men, it was on the rise in the younger age groups. The incidence rate of CRFs was strongly related to age, and, with the exception of dyslipidemia, was higher in the older age groups. CONCLUSION: Cardiovascular risk factors are common in the adult population, while their prevalence and clustering are more prevalent in seniors. Apart from dyslipidemia, the risk of CRFs is appreciably age-related, and higher in seniors.

Programmed cell death 1 expression and Epstein-Barr virus infection in chronic lymphocytic leukaemia: a prospective cohort study.

PURPOSE: Infection with Epstein-Bar virus (EBV) is associated with an unfavourable prognosis in chronic lymphocytic leukaemia (CLL), but the underlying mechanisms remain unknown. We aimed to establish whether EBV worsens the course of CLL by up-regulating the programmed cell death 1 expression. PATIENTS AND METHODS: Using polymerase chain reaction, we measured EBV DNA in the blood of 110 newly diagnosed, treatment-naïve patients with CLL. We used flow cytometry to measure the expression of programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand (PD-L1) on CD4+, CD8+, and CD19+ cells. Additionally, PD-1 and PD-L1 serum concentrations were measured using enzyme-linked immunosorbent assays. We related the expressions of PD-1 and PD-L1 to EBV DNA load and clinical outcomes. RESULTS: Fifty-nine (54%) patients had detectable EBV DNA [EBV(+)], and these patients had more advanced disease at baseline than the rest. PD-1 and PD-L1 serum concentrations and their expressions on all cell populations were higher in EBV(+) than EBV(-) patients. EBV load correlated positively with unfavourable clinical markers of CLL and the expression of PD-1 and PD-L1 on CD4+ and CD8+ cells (rho =0.42-0.75; p<0.001). EBV(+) patients had increased risks of treatment initiation and lymphocyte doubling during a median follow-up period of 32 months (p<0.001). Among EBV(+), but not EBV(-), patients, higher expressions of PD-1 and PD-L1 on CD4+ and CD8+ cells were associated with higher risks of treatment initiation and lymphocyte doubling (p≤0.020). CONCLUSION: EBV-induced up-regulation of PD-1-PD-L1 expression is associated with worse outcomes in CLL.

WHO recommendations on physical activity versus compliance rate within a specific urban population as assessed through IPAQ survey: a cross-sectional cohort study.

OBJECTIVE: The study was designed to address the following three key areas, that is, (1) evaluate overall level of physical activity in the residents of a mid-sized, Central-European city, (2) compliance level with WHO's recommendations on physical activity in leisure time and (3) actual impact of select socioeconomic factors on the physical activity level within the study population. METHODS: Assessment of the source data collected for 4619 participants (1532 men and 3087 women, aged 45-65 years; mean age 56.41±5.31 years) was completed. Three levels of physical activity, and compliance level with pertinent WHO recommendations was evaluated, based on International Physical Activity Questionnaire (long form). Multilevel logistic regression models of socioeconomic factors associated with moderate-level, high-level physical activity, and WHO recommendations were developed. RESULTS: Data analyses revealed that 6.19% of the study participants (n=286) engaged in low-level physical activity, 48.86%-in moderate-level activity, while high-level activity was reported in 44.94% of them. Compliance with pertinent WHO recommendations was higher in men aged 44-55 years, boasting upper-level education, living without a partner and in the persons with a net income over €1140 per household. CONCLUSIONS: Overall level of physical activity in the residents of a mid-sized, Central-European city was established as moderate. Pertinent WHO recommendations on physical activity were met by 4.2% of the subjects only.

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.

Retrospective evaluation of the effectiveness of radiotherapy in patients with plantar fascitis (heel spurs).

AIM: The aim of the study was the evaluation of the effectiveness of radiotherapy in patients with the feet pain caused by heel spurs. BACKGROUND: Treatment options for patients reporting these symptoms include use of suitable orthopedic footwear, the use of general or topical non-steroidal anti-inflammatory drugs or steroids, physiotherapy, manual therapy, shock wave or appropriate surgical procedures. Radiotherapy is one of the method used in patients with chronic pain syndrome. MATERIALS AND METHODS: The material consisted of 47 patients treated in Radiotherapy Department at the Holycross Cancer Center. The time of follow-up ranged from 1 to 129 months. After treatment patients were observed. RESULTS: During the first follow-up visit a complete relief of symptoms was observed in 37 patients, and the pain was felt by 10 patients for 4 months after the treatment. One patient was re-irradiated 6 months after treatment because of persistent pain. At 16 and 17 months after the onset of treatment, pain was reported by two patients. These patients were re-irradiated. One patient had recurrence of pain 48 months after completion of radiation. After the second irradiation the pain was relieved. The remaining patients, with the exception of two, experienced remission of pain, which has been documented. Tolerance of the treatment was very good. No complications of radiation were observed. CONCLUSIONS: Radiotherapy remains an attractive treatment for patients with inflammation of the heel fascia.

Identifying predictive motor factors for falls in post-menopausal breast cancer survivors.

OBJECTIVE: Breast cancer treatment, including radical surgery, is also pursued as late as the 7th - 8th decade of women's lives. Standard physical rehabilitation procedures offered to those women are predominantly focused on attenuating specific functional deficits of the upper limb and trunk. Seldom do they entail any regimens specifically aimed at recovering overall functionality, and reducing exposure to falls-risk. The study aimed to assess potential interrelationships between the self-reported falls, individual functional capabilities and appreciably reducing exposure to falls-risk in a group of post-menopausal, post-surgical breast cancer survivors. METHODS: The study recruited 102 women (aged 65-79; mean age 70.2), post-surgical breast cancer survivors. The subjects were stratified by age into three groups: Group 1 (65-69 years); Group 2 (70-74 years), and Group 3 (75-79 years). Individual functional capabilities were assessed with Eight-foot up & go test (8UG), chair stand test (CST), and 2-minute step test (2ST). Tinetti POMA test was applied to assess gait and balance disorders. Self-reported falls in the past year were ascertained through a questionnaire. RESULTS: Assessment of individual aerobic endurance (2ST) also demonstrated a clear deficit in the mean scores category in all respective age sub-groups, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values; the oldest subjects demonstrating the largest deficit. The aerobic endurance tests results significantly impacted the ultimate assessment of an individual falls-risk in the oldest group. The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such incidents. CONCLUSION: An individual exposure to falls-risk was found to be appreciably more dependent upon individual aerobic endurance rather than overall strength of the lower part of the body in the breast cancer survivors over 75.