Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors.

Introduction: Corticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing's disease (CD), however, some remain clinically silent. Recurrent USP8, USP48, BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs. Methods: Study included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8, USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry. Results: USP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke's cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency. Conclusions: We confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD.

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.

Utility of Immunohistochemistry With Antibodies to SS18-SSX Chimeric Proteins and C-Terminus of SSX Protein for Synovial Sarcoma Differential Diagnosis.

Synovial sarcoma is a relatively common soft tissue tumor characterized by highly specific t(X;18)(p11;q11) translocation resulting in the fusion of SS18 with members of SSX gene family. Typically, detection of SS18 locus rearrangement by fluorescence in situ hybridization or SS18 :: SSX fusion transcripts confirms the diagnosis. More recently, immunohistochemistry (IHC) for SS18-SSX chimeric protein (E9X9V) and C-terminus of SSX (E5A2C) showed high specificity and sensitivity for synovial sarcoma. This study screened a cohort of >1000 soft tissue and melanocytic tumors using IHC and E9X9V and E5A2C antibodies. Three percent (6/212) of synovial sarcomas were either negative for SS18-SSX or had scattered positive tumor cells (n=1). In these cases, targeted RNA next-generation sequencing detected variants of SS18 :: SSX chimeric transcripts. DNA methylation profiles of 2 such tumors matched with synovial sarcoma. A few nonsynovial sarcoma tumors (n=6) revealed either focal SS18-SSX positivity (n=1) or scattered positive tumor cells. However, targeted RNA next-generation sequencing failed to detect SS18 :: SSX transcripts in these cases. The nature of this immunopositivity remains elusive and may require single cell sequencing studies. All synovial sarcomas showed positive SSX IHC. However, a mosaic staining pattern or focal loss of expression was noticed in a few cases. Strong and diffuse SSX immunoreactivity was also seen in epithelioid sclerosing osteosarcoma harboring EWSR1 :: SSX1 fusion, while several sarcomas and melanocytic tumors including cellular blue nevus (5/7, 71%) revealed focal to diffuse, mostly weak to intermediate SSX staining. The SS18-SSX and SSX IHC is a useful tool for synovial sarcoma differential diagnosis, but unusual immunophenotype should trigger molecular genetic testing.

The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment.

BACKGROUND: A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. METHODS: Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. RESULTS: Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. CONCLUSIONS: Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.

Alterations in key signaling pathways in sinonasal tract melanoma. A molecular genetics and immunohistochemical study of 90 cases and comprehensive review of the literature.

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.

Didymium pseudonivicola: A new myxomycete from the austral Andes emerges from broad-scale morphological and molecular analyses of D. nivicola collections.

A new nivicolous myxomycete is described as a result of a comprehensive study of Didymium nivicola collections from the entire range of its occurrence. Statistical analysis of 12 morphological characters, phylogenetic analyses of nuc 18S rDNA and elongation factor 1-alpha gene (EF1A), and a delimitation method (automatic barcode gap diversity) have been applied to corroborate the identity of the new species. A preliminary morphological analysis of D. nivicola revealed high variability of South American populations where four types of spore ornamentation were noted. However, results of molecular study and statistical analysis of morphological characters did not support recognition of these four forms but the distinction of two morphotypes. Consequently, two species have been recognized: D. nivicola and the newly proposed D. pseudonivicola. The new species can be distinguished from D. nivicola by distinctly larger and mostly plasmodiocarpic sporophores, which are scattered to gregarious, paler spores, and by the paler, more delicate and more elastic capillitium. Spore ornamentation of D. pseudonivicola is uniform and can be described as distinctly spiny (pilate under scanning electron microscope [SEM]), whereas those of D. nivicola is more variable, where spines (pilae under SEM) are delicate, distinct, or conspicuous. Additionally, whereas D. nivicola is a species distributed worldwide, D. pseudonivicola occurs only in the austral Andes of Argentina and Chile.

Pack-year cigarette smoking affects the course of palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease with poorly understood pathogenesis. The disease has a chronic course with improvements and exacerbations. Due to palmoplantar location, PPP has a severely negative impact on patients' quality of life. OBJECTIVES: To identify demographic and environmental factors, concomitant diseases, medications, and bacterial factors which may affect the course of PPP. MATERIAL AND METHODS: A total of 51 patients suffering from PPP took part in the study. They were classified according to the Palmoplantar Pustulosis Psoriasis Area and Severity Index (ppPASI) into 3 groups due to the severity of the disease. Pack-year of smoking score was established as a quotient of packets smoked every 24 h and the years of being addicted. Diagnosis of metabolic syndrome was based on the IDF criteria from 2009. Chlamydia trachomatis was detected using enzyme-linked immunosorbent assay (ELISA) technique, Staphylococcus aureus by the culture swabs. Contact hypersensitivity was examined with the T.R.U.E. test. RESULTS: Significantly high severity of PPP was observed in patients addicted to smoking with a high pack-year score (p = 0.03). Significantly lower intensity of PPP lesions was observed in patients treated with ibuprofen (p < 0.01). There was no correlation between severity of PPP skin lesions and comorbidities. CONCLUSIONS: Addiction to cigarette smoking and a high pack-year score aggravates the course of PPP. Treatment with ibuprofen can improve the course of the disease.

Palmoplantar pustulosis: Factors causing and influencing the course of the disease.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disease, most often occurring in middle-aged women. In the course of the condition, painful skin lesions appear on the hands and feet, i.e., areas that are extremely important in everyday life. Therefore, the disease significantly reduces quality of life. The pathogenesis of this disease is poorly understood, although it is known that genetic, immunological and environmental factors play a role in its development. Clinical observations confirm the role of nicotine and contact allergens in the development of the lesions. The skin lesions can also occur as a side effect of certain medications. In some cases, PPP coexists with other diseases, i.e., seronegative arthropathies, as well as celiac and thyroid diseases. There is also a connection between the disease and infectious bacterial foci. Exacerbation of the skin lesions is triggered by stress. Therefore, patients require multidirectional tests, since finding the cause of the disease is essential to administering effective treatment.

Influence of social competence of physicians on patient compliance with osteoporosis medications--a study on Polish postmenopausal women.

OBJECTIVE: The aim of the study was to examine the impact of social competence of physicians on the effectiveness of patient compliance and persistence with therapy. MATERIAL AND METHODS: The study included physicians and their patients, previously diagnosed with osteoporosis, and eligible to receive pharmacological treatment. The physicians were evaluated with the social competence questionnaire involving three dimensions: social exposure, intimacy and assertiveness, as well as in the combined scale. All patients in the study group were prescribed the same medication: alendronate once a week. Compliance and persistence of the patients were juxtaposed with social interaction skills of physicians during 7 scheduled appointments at 2-month intervals. RESULTS: Doctor's effectiveness in situations demanding close interpersonal contact was higher in the group with good compliance--group A (p < 0.001), as well as in the situations of social exposure, (p < 0.001). On the other hand, their assertiveness was higher in the group with poor compliance--group B (p < 0.001). Co-morbid conditions (group A: 76%, group B: 74%), as well as earlier fractures (40.43% vs. 36.78%) were comparable in both groups. Disease acceptance and suggested methods of treatment were more often accepted by patients from group A than group B (56% vs. 33%, respectively). CONCLUSIONS: (1) Disease acceptance is essential for effective treatment. (2) Social skills of physicians influence patient adherence to therapy recommendations. (3) Close interpersonal contact between physicians and their patients eliminates the feeling of fear and

[The role of anorexia nervosa in secondary osteoporosis development with the risk for low energy fractures]. / Rola jadlowstretu psychicznego w rozwoju wtórnej osteoporozy z uwzglednieniem ryzyka zlaman kosci.

Anorexia nervosa (AN) has in recent years become considerably more common. The disease primarily affects girls and young women, also boys and young men. AN is a risk factor for secondary osteoporosis. AN-related metabolic disturbances lead to diminished bone quality and increased risk of fractures. The consequences of low energy fractures are the main causes of death in women with AN. Hormonal disturbances (e.g. hypoestrogenism, increased levels of ghrelin and Y peptide, changes in leptin and endocannabinoid levels), as well as the mechanisms involved in bone resorption (RANK/RANKL/OPG system), are considered to be of great importance for anorectic bone quality. The risk for osteoporotic, non-vertebral fractures in AN patients is significantly higher than in healthy women. Improvement of bone mineral density is possible after substantial body mass increase. Weight loss, in conjunction with a well-balanced, controlled diet, is the key to correct peak bone mass levels, and diminishes the risk for osteoporosis with its consequence of low energy bone fractures.

Association between estrogen receptor alpha gene polymorphisms and bone mineral density in Polish female patients with Graves' disease.

Graves' (GD) hyperthyroidism leads to reduced bone mineral density (BMD) accompanied by accelerated bone turnover. Ample studies have identified association between estrogen receptor (ESR1) gene polymorphism and decreased BMD and osteoporosis. In contrast, number of publications that link ESR1, BMD and Graves' disease is limited. The purpose of this study was to identify the association between ESR1 polymorphisms and BMD in premenopausal women with GD and to determine whether ESR1 polymorphic variants can predispose to GD. The study included 75 women aged 23-46 years with GD and 163 healthy controls. BMD was measured at lumbar spine and femoral neck. We investigated two SNPs in the ESR1 gene and analyzed genetic variants in the form of haplotypes reconstructed by statistical method. Three out of four possible haplotypes of the PvuII and XbaI restriction fragment length polymorphisms were found in GD patients: px (55.3 %), PX (33.3 %) and Px (11.4 %). Women homozygous for xx of XbaI and for pp of PvuII had the lowest BMD at lumbar spine. Moreover, the px haplotype predisposed to reduced lumbar BMD. No associations were observed for femoral neck BMD. No statistically significant relationship were found between ESR1 polymorphisms or their haplotypes and GD. These results indicate that the PvuII and the XbaI polymorphisms of ESR1 gene are associated with bone mineral density in premenopausal women with GD and may help to estimate the risk of bone loss particularly at lumbar spine. However, none of the ESR1 gene alleles predict the risk of GD in Polish female patients.

A discussion of the intervention thresholds in osteoporosis treatment in Poland.

INTRODUCTION: Epidemiological prognoses regarding the global spread of post-menopausal osteoporosis can prove somewhat nebulous. But it is clear that low-energy fractures and their consequences will become an increasingly serious health problem. Therefore it is crucial to implement prognostic procedures which could more effectively predict the incidence of osteoporosis and its complications. MATERIAL AND METHODS: The study involved 378 female patients aged 40-86 years for whom clinical risk factors of osteoporotic fracture were analysed. Densitometry (DPX) was performed at femoral neck. The 10-year risk of fracture was assessed according to the British model of FRAX calculator. RESULTS: The study group was divided into two, depending on the history of low-energy fractures. Previous osteoporotic fractures were confirmed in 128 patients. In this group, the mean bone mineral density (BMD) values (0.717 g/cm(2)) were lower than in the group without fracture history (0.735 g/cm(2)). In 33.3% of patients aged 50-59 years and 17% of women aged 60-79 who required medical treatment for their clinical status (previous fracture), the FRAX value did not meet the criterion of pharmacotherapy administration. Considering BMD in the calculation of FRAX produced an even higher underestimation of the fracture risk. Of women aged 40-49, 25% were qualified for pharmacotherapy of osteoporosis. In that particular age category, BMD did not affect the FRAX value. BMD measurement had a higher discriminatory value among patients aged 50-79, increasing the number of patients requiring therapy by more than 50%. CONCLUSIONS: 1. The FRAX calculator does not always consider the history of low-energy fractures as a criterion sufficient for therapy implementation. 2. Designing a FRAX calculator specifically for the Polish population would be advisable.

The role of anorexia nervosa in secondary osteoporosis development with the risk for low energy fractures.

Anorexia nervosa (AN) has in recent years become considerably more common. The disease primarily affects girls and young women, and also boys and young men. AN is a risk factor for secondary osteoporosis. AN-related metabolic disturbances lead to diminished bone quality and increased risk of fractures. The consequences of low energy fractures are the main causes of death in women with AN. Hormonal disturbances (e.g. hypoestrogenism, increased levels of ghrelin and Y peptide, changes in leptin and endocannabinoid levels), as well as the mechanisms involved in bone resorption (RANK/RANKL/OPG), are considered to be of great importance for anorectic bone quality. The risk of osteoporotic, non-vertebral fractures in AN patients is significantly higher than in healthy women. An improvement of bone mineral density is possible after substantial body mass increase. Weight loss, in conjunction with a well-balanced, controlled diet, is the key to correct peak bone mass levels, and diminishes the risk of osteoporosis with its consequence of low energy bone fractures. (Pol J Endocrinol 2011; 62 (1): 45-47).

Influence of lean and fat mass on bone mineral density (BMD) in postmenopausal women with osteoporosis.

Despite known positive association between body mass and bone mineral density (BMD), relative contribution of fat and lean tissue to BMD remains under debate. We aimed at investigating the effect of selected anthropometric parameters, including fat content and lean body mass (LBM) on BMD in postmenopausal, osteoporotic women with body mass index (BMI) > 20 kg/m(2). The study involved 92 never-treated women (mean age 69.5 ± 7.3). L1-L4 and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA). Absolute (kg) and relative (%) fat and LBM were assessed by means of electric bioimpedance method. We showed both FN and L1-L4 BMD were positively correlated with body mass, waist circumference (WC), hip circumference (HC) and LBM (kg). Fat content correlated with FN BMD (r = 0.36, p < 0.001). Regression analysis revealed the only predictor of L1-L4 BMD was LBM (R(2) = 0.18, p < 0.05), for FN--both LBM and fat (R(2) = 0.18, p < 0.05 and p < 0.001, respectively). Of the women, 44.5% were overweight, 18.4% obese. Obese women displayed the highest BMD. Both L1-L4 and FN BMD were higher in women with WC > 80 cm. In postmenopausal osteoporotic women with BMI > 20 kg/m(2) both fat and lean tissue might contribute to BMD. Positive association between body mass and BMD does not make obesity and osteoporosis mutually exclusive.

Vitamin D supplementation in adults - guidelines.

Vitamin D is necessary in maintaining appropriate calcium and phosphate homeostasis in the body (classical function) and ensuring appropriate functioning of many tissues, organs and cells, unrelated to mineral economy (non-classical function). Vitamin D deficiency in adults may cause osteomalacia, increase fracture risk in osteoporosis, induce cardiovascular diseases, diabetes type 1 and 2, multiple sclerosis, Lesniowski-Crohn disease, and cancer, including colon, breast, and prostate cancer. Possible causes of vitamin D deficiency in a healthy population include decreased cutaneous synthesis and an inadequate intake of vitamin D, both in food and in supplements. Vitamin D deficiency level (25(OH) D. 〈 20 ng/mL), is fairly widespread, being found in a substantial percentage of healthy subjects around the world, regardless of race, gender and age. Daily vitamin D dose, as determined by the Food and Nutrition Board in 1997, is now rather insufficient, the biggest problem being associated with maximal vitamin D levels (50 µg/day) in actually available food supplements. Nowadays, it is recommended that adults need a minimum of 800-1,000 U/day when their exposure to the sun is inadequate (in Poland from October to April). This dosage should be provided to all subjects who avoid sunlight, as well as to those aged over 65 because of their slower skin synthesis of vitamin D and for its proven anti-fracture and anti-fall effects.

[Vitamin D supplementation in adults--guidelines]. / Suplementacja witaminy D u osób doroslych--wytyczne.

Vitamin D is necessary in maintaining appropriate calcium and phosphate homeostasis in the body (classical function) and ensuring appropriate functioning of many tissues, organs and cells, unrelated to mineral economy (non-classical function). Vitamin D deficiency in adults may cause osteomalacia, increase fracture risk in osteoporosis, induce cardiovascular diseases, diabetes type 1 and 2, multiple sclerosis, Lesniowski-Crohn disease, and cancer, including colon, breast, and prostate cancer. Possible causes of vitamin D deficiency in a healthy population include decreased cutaneous synthesis and an inadequate intake of vitamin D, both in food and in supplements. Vitamin D deficiency level (25(OH) D. <20 ng/mL), is fairly widespread, being found in a substantial percentage of healthy subjects around the world, regardless of race, gender and age. Daily vitamin D dose, as determined by the Food and Nutrition Board in 1997, is now rather insufficient, the biggest problem being associated with maximal vitamin D levels (50 µg/day) in actually available food supplements. Nowadays, it is recommended that adults need a minimum of 800-1,000 U/day when their exposure to the sun is inadequate (in Poland from October to April). This dosage should be provided to all subjects who avoid sunlight, as well as to those aged over 65 because of their slower skin synthesis of vitamin D and for its proven anti-fracture and anti-fall effects.

Gender makes the difference: the influence of patients' gender on the delivery of preventive services in primary care in Poland.

OBJECTIVE: General practitioners' (GPs') time and resources for preventive services needs to be delivered equitably. We aimed to study the effect of patients' gender on the delivery of preventive procedures to adult patients aged 40 years and over. METHOD: An observational study was performed in primary care surgeries in Wielkopolska (Poland) as a part of the Improving Quality in Primary Care (PIUPOZ) programme carried out by Family Medicine Department of the University of Medical Sciences, Poznan. Trained observers directly observed GPs in their office, to register preventive procedures performed during the consultation and in the previous year (via the medical record) in patients aged 40 years and over. RESULTS: A total of 1073 preventive procedures were registered among 450 patients (267 women and 183 men) by 113 doctors in one year. The most common were serum glucose, blood pressure and total cholesterol measurements. Six procedures were offered to less than 10% of patients: dietary advice, tobacco use and alcohol screening, exercise counselling, body mass index (BMI) recording, and waist measurement. Men were more likely to receive tobacco use and alcohol screening and BMI measurement, while more women were offered a total cholesterol screen. CONCLUSIONS: The annual delivery rate of preventive procedures in patients aged 40 years and above is below the recommended level set by the Polish Ministry of Health. Procedures based on clinical examinations or laboratory tests were offered and performed more frequently than lifestyle advice. More men than women received preventive services for tobacco use or alcohol screening and BMI measurements. Patients' gender and physicians' engagement may influence GPs' preventive attitude and performance. These elements should be incorporated in the development of guidelines concerning prevention in primary care.

[Efficacy of densitometry and fracture risk assessment tool FRAX in making therapeutic decisions in osteoporosis--a study on female patients of university of medical sciences endocrinology outpatient clinic]. / Znaczenie densytometrii oraz zastosowania metody szacowania ryzyka zlamania osteoporotycznego za pomoca algorytmu FRAX dla podejmowania decyzji terapeutycznych w osteoporozie na przykladzie pacjentek Poradni Endokrynologicznej Uniwersytetu Medycznego w Poznaniu.

INTRODUCTION: Contemporary understanding of osteoporosis is based on the assessment of fracture risk. Evaluation of clinical risk factors of fracture with or without densitometry (DEXA) allows to identify patients requiring pharmacological treatment. AIM: The aim of the study was to estimate the usefulness of DEXA in assessment of fracture risk in women >50 years old. MATERIALS AND METHODS: In 296 previously untreated for osteoporosis women of Endocrinology Outpatient Clinic aged 50 to 85 years (mean 68.8+/-7.8) 10-year fracture risk using FRAX tool was computed from clinical risk factors alone (FRAX, FRAX hip) and after measurement of BMD (FRAX BMD). Then FRAX parameters were compared in 4 age categories. Fracture risk was confronted with therapeutic thresholds proposed in Poland. RESULTS: 10-year fracture risk by FRAX increased with age. The most frequent risk factors were: previous fracture and family history of fractures. FRAX and FRAX BMD were significantly different in the 50-59 year-olds and 60-69 year-olds. Statistically significant difference was found for FRAX hip and FRAX hip BMD in 50-59 year old women. FRAX and FRAXhip were better predictors of fractures than FRAX BMD in patients >80 years old. In 50-79 year old women qualification for treatment was more effective when risk was assessed according to FRAX BMD. DEXA performance did not change the number of women over 80 who were eligible for treatment according to FRAX. CONCLUSIONS: BMD is crucial for the 10-year risk assessment in 50-69 year-olds without previous fracture, as an increasing number of patients need therapy. In >80 year old women clinical risk factors alone are sufficient to make therapeutic decisions. DEXA in these women has no influence on the risk of future fractures, including hip fracture. In 60-69 women with previous fracture DEXA is a good predictor for future fractures but has no value as far as therapeutic decisions are concerned.

Reasons for visiting Polish primary care practices by patients aged 18-44 years: the largest emigrating age group.

Over 3% of the entire Polish population migrate for a job within the European Union, most are aged 18-44 years. The main destinations are Germany, the United Kingdom and Ireland. Immigration is connected with the use of many public services, including healthcare services. Assuming Polish immigrants require medical consultations in the countries they reside in, the authors have analysed the reasons for patients' visits to general practitioners (GPs) in Poland in order to predict possible reasons why Polish patients living abroad may make appointments with GPs in other countries. Data from 22,769 visits to GP practices between June 2005 and May 2006 by Polish patients aged 18-44 years were collected electronically. Age was categorised into three groups (18-24, 25-4 and 35-44 years) and the reason for the visit was categorised according to the ICD 10 coding system. Among the 12,535 patients registered with GPs, 73.1% of women and 68.6% of men required consultations during the year the study was conducted. The highest percentage of visits was recorded for women aged 35-44 years, while men of the same age were the least likely to visit a GP. The mean number of visits per patient ranged from 1.89 for men aged 25-34 years to 3.11 for women aged 35-44 years. The means were similar for 18- to 24-year-old men and women. Women aged 35-44 years had a higher mean number of visits compared with women aged 18-4 years, whereas the opposite was true for men. The analysis of reasons for visits within the age groups indicated that the percentage of appointments for respiratory problems and general and unspecified problems dropped by more than half from the 18-24-year-olds to the 35-44-years-olds, while visits for musculosceletal, cardiovascular, and mental and behavioural problems increased by a factor of four. The presented results intend to enable healthcare services meet Polish immigrants' healthcare needs.

Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease.

UNLABELLED: Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). IN CONCLUSION: VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development.