Anti-resorptive therapy in the osteometabolic patient affected by periodontitis. A joint position paper of the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP).

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior.

The orthogeriatric comanagement improves clinical outcomes of hip fracture in older adults.

Treatment of older adults with hip fracture is a healthcare challenge. Orthogeriatric comanagement that is an integrated model of care with shared responsibility improves time to surgery and reduces the length of hospital stay and mortality compared with orthopedic care with geriatric consultation service and usual orthopedic care, respectively. INTRODUCTION: Treatment of fractures in older adults is a clinical challenge due partly to the presence of comorbidity and polypharmacy. The goal of orthogeriatric models of care is to improve clinical outcomes among older people with hip fractures. We compare clinical outcomes of persons with hip fracture cared according to orthogeriatric comanagement (OGC), orthopedic team with the support of a geriatric consultant service (GCS), and usual orthopedic care (UOC). METHODS: This is a single-center, pre-post intervention observational study with two parallel arms, OGC and GCS, and a retrospective control arm. Hip fracture patients admitted to the trauma ward were assigned by the orthopedic surgeon to the OGC (n = 112) or GCS (n = 108) group. The intervention groups were compared each with others and both with the retrospective control group (n = 210) of older adults with hip fracture. Several clinical indicators are considered, including time to surgery, length of stay, in-hospital, and 1-year mortality. RESULTS: Patients in the OGC (OR 2.62; CI 95% 1.40-4.91) but not those in the GCS (OR 0.74; CI 95% 0.38-1.47) showed a higher probability of undergoing surgery within 48 h compared with those in the UOC. Moreover, the OGC (ß, - 1.08; SE, 0.54, p = 0.045) but not the GCS (ß, - 0.79; SE, 0.53, p = 0.148) was inversely associated with LOS. Ultimately, patients in the OGC (OR 0.31; CI 95 % 0.10-0.96) but not those in the GCS (OR 0.37; CI 95% 0.10-1.38) experienced a significantly lower 1-year mortality rate compared with those in the UOC. All analyses were independent of several confounders. CONCLUSIONS: Older adults with hip fracture taken in care by the OGC showed better clinical indicators, including time to surgery, length of stay and mortality, than those managed by geriatric consultant service or usual orthopedic care.

Partnering with carryouts: implementation of a food environment intervention targeting youth obesity.

Youth obesity is a major public health problem in the United States, especially among urban-based, minority youth. The B'More Healthy Communities for Kids (BHCK) trial worked at multiple levels of the food environment, including carryouts, to increase access to and demand for healthy, affordable foods. The objective of this article is to describe the development and implementation of BHCK's carryout intervention. Process evaluation was conducted to assess intervention reach (number of interactions with youth and adults either in person or on social media), dose delivered (number of food samples and promotional materials distributed, social media posts and meetings with owners) and fidelity (availability of promoted items). Overall, the carryout intervention showed moderate to optimal reach, moderate to optimal dose delivered and moderate to optimal fidelity. These findings demonstrate a successfully implemented carryout intervention in a low-income urban setting. Lessons learned about new methods for engaging the community and increasing demand for healthy food can be used to inform future studies and programs to improve the food environment.

Implementation of B'More Healthy Communities for Kids: process evaluation of a multi-level, multi-component obesity prevention intervention.

B'More Healthy Communities for Kids was a multi-level, multi-component obesity prevention intervention to improve access, demand and consumption of healthier foods and beverages in 28 low-income neighborhoods in Baltimore City, MD. Process evaluation assesses the implementation of an intervention and monitor progress. To the best of our knowledge, little detailed process data from multi-level obesity prevention trials have been published. Implementation of each intervention component (wholesaler, recreation center, carryout restaurant, corner store, policy and social media/text messaging) was classified as high, medium or low according to set standards. The wholesaler component achieved high implementation for reach, dose delivered and fidelity. Recreation center and carryout restaurant components achieved medium reach, dose delivered and fidelity. Corner stores achieved medium reach and dose delivered and high fidelity. The policy component achieved high reach and medium dose delivered and fidelity. Social media/text messaging achieved medium reach and high dose delivered and fidelity. Overall, study reach and dose delivered achieved a high implementation level, whereas fidelity achieved a medium level. Varying levels of implementation may have balanced the performance of an intervention component for each process evaluation construct. This detailed process evaluation of the B'More Healthy Communities for Kids allowed the assessment of implementation successes, failures and challenges of each intervention component.

Early post-surgical cognitive dysfunction is a risk factor for mortality among hip fracture hospitalized older persons.

This study investigates the relationship between cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality among 514 hip fracture hospitalized older persons. Patients with early cognitive dysfunction or delirium experienced a 2-fold increased mortality risk. Early post-operative cognitive dysfunction and delirium are negative prognostic factors for mortality. BACKGROUND AND PURPOSE: Premorbid cognitive impairment and dementia in older individuals negatively affect functional recovery after hip fracture. Additionally, post-operative delirium is an established risk factor for negative outcomes among hip fracture patients. While the majority of hip fracture patients experience minor post-surgical cognitive dysfunction, the prognostic value of this phenomenon is unknown. Therefore, we investigated the relationship between minor cognitive dysfunction or delirium detected in the early post-surgical phase and the 1-year mortality after index hip fracture. SUBJECTS AND METHODS: We enrolled 514 patients with hip fracture (77.4 % women), aged 65 years or older (mean age 83.1 ± 7.3 years), who underwent surgical hip fracture repair. Patients were assessed daily from the second to the fourth post-operative day and at 3, 6, and 12 months thereafter. All participants underwent comprehensive assessment, including detection of delirium by using the confusion assessment method and evaluation of cognitive function by using mini-mental state examination (MMSE; score range 0 to 30, with lower scores indicating poorer performance). In the absence of delirium, post-surgical cognitive dysfunction was defined as having low performance on MMSE. Vital status of 1 year after the index fracture and date of death were gathered from local registries. RESULTS: The observed 1-year mortality rate was 14.8 %. Men were more likely to die than women within 1 year of the index fracture (p < 0.01). Compared to participants with better cognitive performance, those with MMSE < 24, as well as those with delirium in the post-operative phase, showed a significantly higher 1-year mortality rate (23.3 versus 17.9 and 8.1 %, respectively). Independent of age and sex, post-operative cognitive dysfunction as well as delirium was both associated with a 2-fold increased mortality risk. CONCLUSIONS: The presence of minor cognitive dysfunction in the early post-surgical phase is a negative prognostic factor for mortality among elderly hip fracture patients. The burden of minor cognitive dysfunction is likely superimposed on that of delirium in subgroups of frail patients.

Association of increased carotid intima-media thickness and lower plasma levels of vitamin C and vitamin E in old age subjects: implications for Alzheimer's disease.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT >1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

Dementia, osteoporosis and fragility fractures: Intricate epidemiological relationships, plausible biological connections, and twisted clinical practices.

Dementia, osteoporosis, and fragility fractures are chronic diseases, often co-existing in older adults. These conditions pose severe morbidity, long-term disability, and mortality, with relevant socioeconomic implications. While in the research arena, the discussion remains on whether dementia is the cause or the consequence of fragility fractures, healthcare professionals need a better understanding of the interplay between such conditions from epidemiological and physiological standpoints. With this review, we summarized the available literature surrounding the relationship between cognitive impairment, dementia, and both low bone mineral density (BMD) and fragility fractures. Given the strength of the bi-directional associations and their impact on the quality of life, we shed light on the biological connections between brain and bone systems, presenting the main mediators, including gut microbioma, and pathological pathways leading to the dysregulation of bone and brain metabolism. Ultimately, we synthesized the evidence about the impact of available pharmacological treatments for the prevention of fragility fractures on cognitive functions and individuals' outcomes when dementia coexists. Vice versa, the effects of symptomatic treatments for dementia on the risk of falls and fragility fractures are explored. Combining evidence alongside clinical practice, we discuss challenges and opportunities related to the management of older adults affected by cognitive impairment or dementia and at high risk for fragility fracture prevention, which leads to not only an improvement in patient health-related outcomes and survival but also a reduction in healthcare cost and socio-economic burden.

Fermentation kinetics of sainfoin hay with and without PEG.

The in vitro gas production technique was applied to evaluate the biological activity of tannins in sainfoin (Onobrychis viciifolia Scop.) hay cut at four progressive phenological stages. The buffalo (Bubalus bubalis) rumen fluid was used as inoculum, polyethylene glycol (PEG) was added as specific binding agent and an alfalfa hay (AH) was used as control. All samples were analysed for chemical composition and condensed tannin (CTs). According to the phenological stage of sainfoin, crude protein gradually decreased [from 219 to 122 g/kg dry matter (DM)] and neutral detergent fibre (NDF) increased (from 391 to 514 g/kg DM). Condensed tannins showed the highest value at the first phenological stage [31.5 mg catechin equivalents (CE)/g DM], and their level significantly decreased at the subsequent growth stages. Gas production and fermentation rate were significantly affected by substrate type and PEG addition. The first stage of sainfoin showed the lowest value of gas and volatile fatty acids production and the slowest fermentation kinetics compared with the other samples, when incubated without PEG, because of the CTs effect. The incubation with PEG improved the fermentation process of the first stage of sainfoin, but no effect was registered on AH, where CTs were not detected. Among the sainfoin samples, the slowest kinetics with PEG was observed in the hay harvested at the fourth stage, probably due to its chemical composition. The use of PEG allowed to verify the effect of tannins on the in vitro fermentation characteristics of sainfoin hay.

Dietary antioxidants as potential pharmacological agents for ischemic stroke.

Acute ischemic stroke is a leading cause of death and severe disability in industrialised countries and also in many developing countries. An excessive amount of free radicals is generated during cerebral ischemia, which significantly contributes to brain damage. Therefore, an increasing interest has been devoted to the potential benefits of antioxidant compounds in ischemic stroke patients. In this review, we examined the most relevant observational studies concerning the relationship between dietary antioxidants and ischemic stroke as well as clinical trials investigating the effects of single or multiple antioxidant supplementation in the prevention or treatment of acute ischemic stroke. Furthermore, we reviewed the most promising antioxidant compounds, i.e. dehydroascorbic acid, alpha-tocotrienol, gamma-tocopherol, flavonoids, resveratrol and gingko biloba, tested in animal models of acute ischemic stroke. Finally, we carefully evaluated the reasons for the discrepancy between experimental and clinical studies, and provided recommendations to improve the translation of the results obtained in animal models to patients with acute ischemic stroke.

Sex hormone binding globulin levels across the adult lifespan in women--the role of body mass index and fasting insulin.

SHBG is a major carrier of androgens. In men, SHBG levels increase with age, while in women data are scant. There is evidence that body mass index (BMI) and fasting insulin influence SHBG concentration. Since low SHBG levels are predictors of insulin resistance and diabetes, understanding the relationship of SHBG with age, insulin, and BMI is important to gain insight into the role of SHBG as a cardiovascular risk factor in women. Differences in SHBG across adult life span and their relationship with insulin and BMI were evaluated in a representative cohort of 616 Italian women free of diabetes and not on hormone replacement therapy enrolled in the InCHIANTI Study. The relationship of SHBG with age, BMI, and fasting insulin levels was analyzed using linear regression and by loess smoother. Serum SHBG levels showed a U-shaped trajectory with age, declining from the 2nd to the 6th decade of life and increasing after the 6th decade (p<0.0001). Age-related trends for BMI and fasting insulin mirrored the trend observed for SHBG. After adjusting for fasting insulin, the relationship between log (SHBG) and age square was attenuated (beta coefficient from 0.00044 to 0.00039) and was further reduced after adjustment for BMI (from 0.00039 to 0.00028). SHBG levels show an age-related U-shaped trajectory. These changes mirror the age-related changes in BMI and fasting insulin, suggesting that BMI and insulin negatively influence SHBG concentration.

Anticholinergic Burden and Functional Status in Older People with Cognitive Impairment: Results from the Regal Project.

OBJECTIVE: The use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment. DESIGN: Cross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer's diseases (AD) (n=1127) subjects. SETTING: Data were gathered from the ReGAl project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large longitudinal Italian multicentric clinical-based study, promoted by the Italian Society of Gerontology and Geriatrics (SIGG). PARTICIPANTS: 2359 outpatients, older than 65 years, admitted to memory clinics. The total sample size, estimated according to a global effect size of 25% with type I error of 0.05 and a power of 95% is 2010 subjects. MEASUREMENT: Functional status was evaluated by the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scales. The drug-related anticholinergic burden was estimated by the Anticholinergic Risk Scale (ARS). RESULTS: The 15.9 % (n=375) of total population used at least one drug with anticholinergic properties. Such a drug use was associated with partially dependence in ADL (OR:1.42, CI95%: 1.10-1.83; p=0.006), independently of gender, number of drugs, comorbidity index, presence of clinically relevant neuropsychiatric symptoms and adjusted MMSE. Anticholinergic drug use was associated with un-ability at each IADL task only in male MCI subjects, with significant impairment in shopping (p=0.011), and drug management (p=0.05). CONCLUSIONS: The use of medications with anticholinergic properties is common among older persons cognitively health as well as with cognitive impairment. Our results suggest that the use of anticholinergic drugs is associated with functional impairment, especially in old age subjects with initial cognitive impairment. Minimizing anticholinergic burden should result in maintaining daily functioning, especially in a vulnerable population, such as MCI and mild AD.

Development of a piezoelectric immunosensor for the measurement of paclitaxel.

This paper describes the development of a piezoelectric immunosensor for the measurement of paclitaxel (taxol), a natural anti-cancer agent. An antibody specific for taxanes was immobilized onto the surface of quartz crystals by means of the layer-by-layer self-assembly technique. The immobilization was achieved using electrostatic interactions between a precursor layer and the antibody molecules. The assembly process was monitored by a quartz crystal microbalance (QCM) and the topography of the modified quartz crystals was investigated by means of atomic force microscopy. The specific interaction of the immobilized antibody with paclitaxel in solution at different concentrations was monitored as a change in resonant frequency of the modified crystal. Moreover, the influence of non-specific adsorption was also characterized. The results show that the proposed immunosensor offers a promising alternative to classical analytical methods for a fast and easy determination of paclitaxel.

Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals.

BACKGROUND: Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. OBJECTIVE: To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. DESIGN: We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. RESULTS: Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. CONCLUSION: Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of prescribing.

Role of antioxidants in atherosclerosis: epidemiological and clinical update.

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents.

Protein-surface interactions: an energy-based mathematical model.

This article describes an energy-based approach to protein adsorption, focusing on the energies involved in the interactions between a protein and a surface. Mathematical modeling and simulation based on this approach allow an improved understanding of the conditions that favor or prevent adsorption of a protein onto a surface and that can play a significant role in the design of material surfaces that interact with biological tissues according to specific needs. Biocompatibility with respect to fluids in motion, such as blood, is the main foreseeable application of our work. The considered energies are the van der Waals energy, the electrostatic energy, and the hydrophobic or hydrophilic energy. Moreover, the motion of the medium in which particles are immersed is also taken into account, considering the drag effect of the motion of the fluid on the particle, leading to a kinetic contribution to the total energy. It is shown that the adsorption behavior is not mainly determined by the van der Waals energy and by the double layer energy, but that a significant role is also played by the hydrophobic or hydrophilic energy. These results support the findings of experimental studies.

[A new method of functional rehabilitation of patients with occupational disability caused by lumbar spine pathology]. / Un nuovo metodo di riabilitazione funzionale (DBC) in pazienti con disabilità lavorativa da patologia del rachide lombare.

Rehabilitation is reducing disability through an improvement of function, i.e. rehabilitation need always to be "functional". Nevertheless, like it happened in other fields where rehabilitation has not yet reached its maturity, in spinal pathologies it has usually been considered equal to conservative treatment, i.e. not surgical relief of pain. But relieving pain does not always mean to recover function: in fact, it has been proven that there are no long term good results treating symptomatically chronic low back pain (CLBP). In the Eighties in USA a new kind of treatment has been introduced for inpatient rehabilitation of CLBP, based on a full-time four-weeks training of physical abilities, together with a cognitive and educational approach to pain. This treatment, named "functional rehabilitation", proved its efficacy also in randomised controlled trials (RCT). In the Nineties in Finland the outpatient version of this treatment for CLBP has been developed by "Documentation Based Care" (DBC), whose efficacy have also been documented in RCT: the efficiency of this last kind of treatment should be higher. DBC treatment is spreading around the world, and it recently reached Italy in Don Gnocchi.

Isolation of T-cell clones with specificity for arterial antigen from spontaneously hypertensive rats.

OBJECTIVE: It has been postulated that hypertension in the spontaneously hypertensive rat (SHR) results from autoimmune damage to the SHR vasculature. The objective of this study was to isolate autoreactive T-cells specific for arterial antigens, and to characterize these cells. DESIGN: The presence of autoreactive T-cells in the SHR has not been studied previously. Lymphocytes were isolated from spleens obtained from SHR and Wistar-Kyoto (WKY) rats aged 4, 8, 12, 16, 20, 24 and 28 weeks. METHODS: Limiting dilution analysis was used to clone and to establish arterial antigen-reactive T-cell clones. The specificity of these clones was assessed by measuring lymphokine production and T-cell proliferation induced by arterial antigen and by irrelevant control antigens. RESULTS: All of the SHR, regardless of age, possessed arterial antigen-specific CD4+, major histocompatability complex class II-restricted T-cells. The responses of freshly isolated spleen cells to arterial antigen were weaker than the proliferative responses of interleukin-2-expanded T-cells to arterial antigen. The T-cell clones also produced interleukin-2, interleukin-4 and interferon-gamma in response to arterial antigen. However, the presence of T-cells specific for arterial antigen is not unique to SHR, since a similar response was seen in normotensive WKY rats. CONCLUSIONS: The results indicate the existence of T-cells specific for arterial antigen in the spleens of both SHR and WKY rats. Thus, arterial antigen-reactive T-cells cannot be the initial cause of hypertension, but the activation of such autoreactive T-cells might be important in the development of hypertension.

Magnetic resonance imaging and high-resolution computed tomography in tumors of the lung and the mediastinum.

Magnetic resonance (MR) imaging and high resolution computed tomography (CT) have been compared in 37 patients who had expansive processes of the lung and the mediastinum. MR imaging and CT scanning gave identical results in 32 patients; in 5 patients, CT scanning has proved more useful in evaluating the stag e of primary lung tumors. MR imaging often gives more information about the actual size of the tumor, and the involvement of close structures, although it does not modify staging of the tumor. MR imaging has the advantage to differentiate hilar adenopathy from blood vessel structures. Evaluation of T2 relaxing time (that we have performed in the same location of thin-needle biopsy aspiration), however, did not prove to be of diagnostic significance; this indicates that MR imaging at the moment is not suitable for tissue typification.

Vitamin D receptor gene polymorphism is associated with metastatic breast cancer.

The vitamin D receptor (VDR) has been detected in breast tumor cells. We tested the hypothesis that VDR gene polymorphism might influence the outcome of women affected by breast cancer. A total of 88 breast cancer patients were recruited: 50 women were affected by newly diagnosed breast cancer whereas 38 women suffered from relapsing disease. The individual genetic pattern for VDR was evaluated by DNA extraction followed by PCR amplification of the VDR gene, and digestion with the restriction enzyme BsmI. In 167 healthy women, participating in the osteoporosis prevention trial and being used as a control, we detected 121 Bb heterozygotes (72%), 26 homozygotes for the bb alleles (16%), and 20 homozygotes for the BB alleles (12%). In the newly diagnosed breast cancer group the occurrence of Bb patients was 58% (29/50); bb patients represented 22% (11/50), and BB cases were 20% (10/50). The VDR frequency distribution in the control and primary disease patient groups was not statistically different. In the metastatic cancer group, the prevalence of the bb genotype (14/38; 37%) was double the percentage of control subjects, whereas the percentage of BB women with metastases was half the control group (2/38; 5%). Women who were homozygous bb appeared to have almost a four times higher risk of developing metastases than BB women. Whatever the molecular mechanisms underlying the VDR effects in cancer cells, we believe that the VDR gene polymorphism may represent an important determinant in the evaluation of women affected by breast cancer and might help design targeted therapy.