Qualitative and quantitative assessment of cartilage degeneration using full-field optical coherence tomography ex vivo.

OBJECTIVE: The purpose of this study was to investigate the ability of full-field optical coherence tomography (FFOCT) to qualitatively and quantitatively evaluate cartilage degeneration using the qualitative evaluation of histology sections as the reference. DESIGN: Thirty-three human knee cartilage samples of variable degeneration were included in the study. A closely matching histology and FFOCT image was acquired for each sample. The cartilage degeneration was qualitatively evaluated by assigning a grade to each histology and FFOCT image. The relevance of the performed grading was assessed by calculating the intra- and inter-observer reproducibility and calculating the concordance between the histology and FFOCT grades. A near-automatic algorithm was developed to quantitatively characterize the cartilage surface in each image. The correlation between the quantitative results and the reference qualitative histology was calculated. RESULTS: An almost perfect agreement was achieved for both the intra- and inter-reproducibility of the histology and FFOCT qualitative grading (κ ≥ 0.91). A high and statistically significant level of agreement was measured between the histology and FFOCT grades (W = 0.95, P < 0.05). Strong and statistically significant correlations were measured between the quantitative results and the reference qualitative histology grades (ρ ≥ 0.75, P < 0.05). CONCLUSIONS: We have demonstrated that FFOCT is an alternative approach to conventional optical coherence tomography (OCT) that is as well adapted for the qualitative and quantitative assessment of human cartilage as the reference gold standard - histology. This study constitutes the first promising results towards developing a new diagnostic tool in the field of osteoarthritis.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Temporal dynamics of hepatitis C genotypes in a five-year hospital-based surveillance in Northern Italy.

Hepatitis C virus (HCV) genotypes have became important epidemiological markers in the management of HCV-infected subjects and infection treatment. The dynamics of HCV genotypes are changing in Europe. During a five-year (2009-2013) hospital-based surveillance in the area of Parma, Northern Italy, serum/plasma samples from 1,265 HCV RNA-positive subjects were genotyped. Subtypes 1b, 3a, and 1a were predominant (32.6 %, 19.1 %, and 17.8 %, respectively), with a correlation between viral load and gender. Subtypes 1a and 3a were more frequent in adults and males with a significant difference with the over-50 age group and females (P > 0.0001). Subtype 1b, as well as 2a/2c and G2 not-subtypeable (15.7 % and 7.2 %, respectively), were more common in females and in the over-50 age group compared to males (P < 0.0001, P < 0.0001, and P < 0.05, respectively) and the under-50 age group (P < 0.0001). While subtype 1b showed a nearly constant trend, subtype 1a peaked in 2012, when a consistent decrease in G2 was observed. The increasing detection of G4, mainly in adults, and subtypes 1a and 3a suggests their epidemiological relevance in the population. The detection of more than one HCV genotype in the same sample (0.2 %) and different genotypes in distant samples (5.1 %) from the same subject reinforces the opinion that re-infection and super-infection with different genotypes are not negligible events, especially in HIV-infected subjects. The dynamics of HCV genotypes could have significant implications for infection control.

[Rigid cystoscopy versus retrovision for adjustable peri-urethral balloons guidance: Comparison of precision thanks to a surgical navigation system]. / Cystoscopie rigide versus rétro-vision pour le guidage des ballonnets péri-urétraux : comparaison de la précision grâce à un système de navigation chirurgicale.

OBJECTIVES: The main goal of our phantom study was to compare the precision of adjustable periurethral balloons positioning depending whether the guidance was obtained by retrovision or rigid cystoscopy. MATERIAL AND METHODS: A navigation guidance system was used to localize the introduction mandrel which was equipped with tracking targets. Two ideal sites of implantation were predefined and recorded into the navigation system. The two points were placed symmetrically to the phantom reproducing the urethra. Four different users were asked to position the tip of the introduction mandrel as close as possible to the ideal site of implantation with the help of each method of guidance. For each attempt, the distance (mm) between the tip of the introduction mandrel and the ideal position was recorded by the navigation system. RESULTS: For each method of guidance, a total of 20 attempts on each side were made by direct puncture on one side and a symmetrical contralateral puncture. For direct puncture, the median distances were 5.20 (±3.96) and 4.38 (±1.55) mm with rigid cystoscopy and retrovision respectively (P=0.29). For symmetrical contralateral puncture, the median distance were 7,19 (±3,78) and 6,86 (±2,76) mm with rigid cystoscopy and retrovision respectively (P=0,32) CONCLUSION: This study could not demonstrate any significant difference between the two guidance systems. Nevertheless, it showed that navigation guidance system could be used to compare the precision of surgical interventions. LEVEL OF EVIDENCE: 4.

Epidemiological and molecular features of norovirus infections in Italian children affected with acute gastroenteritis.

During a 5-year (2007-2011) surveillance period a total of 435 (15·34%) of 2834 stool specimens from children aged <14 years with acute gastroenteritis tested positive for norovirus and 217 strains were characterized upon partial sequence analysis of the polymerase gene as either genogroup (G)I or GII. Of the noroviruses, 99·2% were GII with the GII.P4 genotype being predominant (80%). GII.P4 variants (Yerseke 2006a, Den Haag 2006b, Apeldoorn 2008, New Orleans 2009) emerged sequentially during the study period. Sequence analysis of the capsid gene of 57 noroviruses revealed that 7·8% were recombinant (ORF1/ORF2) viruses including GII.P7_GII.6, GII.P16_GII.3, GII.P16_GII.13, GII.Pe_GII.2, and GII.Pe_GII.4, never identified before in Italy. GII.P1_GII.1, GII.P2_GII.1, GII.P3_GII.3 and GII.P6_GII.6 strains were also detected. Starting in 2011 a novel GII.4 norovirus with 3-4% nucleotide difference in the polymerase and capsid genes from variant GII.4 New Orleans 2009 was monitored in the local population. Since the epidemiology of norovirus changes rapidly, continuous surveillance is necessary to promptly identify the onset of novel types/variants.

Dew condensation on desert beetle skin.

Some tenebrionind beetles inhabiting the Namib desert are known for using their body to collect water droplets from wind-blown fogs. We aim to determine whether dew water collection is also possible for desert insects. For this purpose, we investigated the infra-red emissivity, and the wetting and structural properties, of the surface of the elytra of a preserved specimen of Physasterna cribripes (Tenebrionidæ) beetle, where the macro-structure appears as a series of "bumps", with "valleys" between them. Dew formation experiments were carried out in a condensation chamber. The surface properties (infra-red emissivity, wetting properties) were dominated by the wax at the elytra surface and, to a lower extent, its micro-structure. We performed scanning electron microscope on histological sections and determined the infra-red emissivity using a scanning pyrometer. The emissivity measured (0.95±0.07 between 8-14 µm) was close to the black body value. Dew formation occurred on the insect's elytra, which can be explained by these surface properties. From the surface coverage of the condensed drops it was found that dew forms primarily in the valleys between the bumps. The difference in droplet nucleation rate between bumps and valleys can be attributed to the hexagonal microstructure on the surface of the valleys, whereas the surface of the bumps is smooth. The drops can slide when they reach a critical size, and be collected at the insect's mouth.

Evidence for recombination between pandemic GII.4 norovirus strains New Orleans 2009 and Sydney 2012.

During 2012, a novel pandemic GII.4 norovirus variant, Sydney 2012, emerged worldwide. A signature of the variant was a GII.Pe ORF1, in association with GII.4 Apeldoorn 2008-like ORF2-ORF3 genes. We report the detection of recombinant GII.4 Sydney 2012 strains, possessing the ORF1 gene of the former pandemic variant New Orleans 2009.

Nationwide surveillance study of human astrovirus infections in an Italian paediatric population.

The study investigated the genetic diversity of human astroviruses (HAstVs) detected in children hospitalized with gastroenteritis in Italy in 2008-2009. A total of 1321 faecal samples were collected in Parma (northern Italy), Bari (southern Italy), and Palermo (Sicily) and screened for the presence of HAstVs. RT-PCR amplification of a portion at the 5'-end of ORF2 allowed the detection of HAstVs in 3·95% of the patients. Four different genotypes (HAstV-1, HAstV-2, HAstV-4, HAstV-5) were found to be circulating during the study period, with HAstV-1 being the predominant type. Interestingly, a novel lineage, proposed as HAstV-2d, was found to have emerged in Parma in 2009. Investigating the genetic variability of HAstVs will be important for understanding the epidemiological trends and evolution of these viruses.

Genetic heterogeneity and recombination in human type 2 astroviruses.

Novel lineages of human astrovirus (HAstV) types 2, 2c, and 2d have been identified. Upon sequencing of the 3' end of the genome, the type 2c and 2d HAstVs were found to be open reading frame 1b (ORF1b)-ORF2 recombinant, with ORF1b being derived from type 3 and type 1 HAstVs, respectively. An ORF2 interlineage recombinant strain, 2c/2b, was also identified.

Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy.

BACKGROUND: To reduce side-effects of corticosteroid-containing antiemetic regimens, tailoring antiemetic schedules to specific requirements of different patients could be of benefit. We evaluated the possibility to reduce the total dose of corticosteroids when palonosetron, a long-acting second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, is used. MATERIALS AND METHODS: Double-blind, multicentre, noninferiority study of chemotherapy-naive breast cancer patients receiving 0.25 mg palonosetron and 8 mg dexamethasone on day 1, randomly assigned to receive placebo (n = 151) or 4 mg b.i.d. dexamethasone (n = 149) on days 2 and 3. Primary end point was complete response (CR) rate (no emesis, no rescue medication) in the overall (days 1-5) period. Secondary end points were CR rates in the acute (day 1) and delayed (days 2-5) periods, rates of no emesis and no nausea and impact on daily functioning (Functional Living Index-Emesis). RESULTS: Noninferiority between the two treatments was demonstrated by similar CR rates (P = 0.487) in the overall period. Most parameters showed that palonosetron and dexamethasone on day 1 only offer chemotherapy-induced nausea and vomiting protection similar to multiple-day dexamethasone administration. CONCLUSION: In patients treated with a single injection of palonosetron on day 1, reducing dexamethasone is an option that is not associated with significant reduction in antiemetic control during the 5-day period or an impact on patient functioning.

Lactobacillus reuteri CRL 1098 prevents side effects produced by a nutritional vitamin B deficiency.

AIMS: To evaluate the efficiency of the vitamin B(12-)producing Lactobacillus reuteri CRL1098 strain in preventing the symptoms caused by a nutritional cobalamin-deficient diet in pregnant female mice and their weaned offspring. METHODS AND RESULTS: Pregnant female mice were divided into three groups: animals fed with a B(12)-deficient diet (DD), animals fed with DD plus L. reuteri CRL1098 and animals fed with a B(12)-sufficient diet. The animals received the different feedings from the end of gestation up to weaning. At the end of the trials, they and their corresponding offspring were bled to determine haematological, immunological and histological parameters. The administration of the pseudovitamin B(12)-producing strain prevented the symptoms observed in female and weaned young animals fed with a nutritional B(12)-deficient diet. CONCLUSIONS: Our data suggest that the pseudovitamin B(12) produced by L. reuteri CRL1098 is biologically active and effective in preventing the pathologies caused by the nutritional deficiency of B(12) both in pregnant mice and their offspring. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability of L. reuteri CRL1098 to prevent a nutritional vitamin deficiency was demonstrated for the first time. The addition of a GRAS micro-organism to complement the B(12) content in deficient foods is an interesting biotechnological alternative.

Prevention of chronic gastritis by fermented milks made with exopolysaccharide-producing Streptococcus thermophilus strains.

Acetyl-salicylic acid (ASA) is a nonsteroidal antiinflammatory/analgesic drug, which may cause gastritis or stomach ulcers if intensively employed. Exopolysaccharide (EPS)-producing lactic acid bacteria have been claimed to induce immunostimulatory/antiulcer effects in the host. This study investigated the potential preventive effect of fermented milks (FM) with EPS-producing Streptococcus thermophilus strains (CRL 1190 and CRL 804) on an in vivo model of chronic gastritis. Fermented milks (2 EPS(+) and 1 EPS(-), separately) were fed to BALB/c mice for 7 d before inducing gastritis with ASA (400 mg/kg of body weight per day for 10 d; gastritis group, n = 5). Appropriate control groups (ASA administered but not given FM, n = 5; and ASA not administered but given FM) were included in this study. Gastric inflammatory activity was evaluated through the stomach's histology and the number of IFNgamma(+) and IL-10(+) cytokine-producing cells in the gastric mucosa. Only mice preventively treated with the EPS-producing Strep. thermophilus CRL 1190 FM and later administered ASA did not develop gastritis, showing a conserved gastric mucosa structure similar to those of healthy mice. A marked decrease of IFNgamma(+)- and increase of IL-10(+)-producing cells compared with the gastritis group mice were observed. Purified EPS from Strep. thermophilus CRL 1190 resuspended in autoclaved milk was also effective for gastritis prevention. The EPS-protein interaction might be responsible for the observed gastroprotective effect; such interactions may be affected by industrial manufacturing conditions. The results indicate that the FM with Strep. thermophilus CRL 1190 or its EPS could be used in novel functional foods for preventing chronic gastritis.

Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications.

BACKGROUND: This study aimed to evaluate the prognostic significance of circulating tumor cells (CTCs) detection in advanced breast cancer patients. PATIENTS AND METHODS: We tested 80 patients for CTC levels before starting a new treatment and after 4, 8 weeks, at the first clinical evaluation and every 2 months thereafter. CTCs were detected using the CellSearch System. RESULTS: Forty-nine patients had >or=5 CTCs at baseline. At the multivariate analysis, baseline number of CTCs was significantly associated with progression-free survival [hazard ratio (HR) 2.5; 95% confidence interval (CI) 1.2-5.4]. The risk of progression for patients with CTCs >or=5 at last available blood draw was five times the risk of patients with 0-4 CTCs at the same time point (HR 5.3; 95% CI 2.8-10.4). Patients with rising or persistent >or=5 CTCs at last available blood draw showed a statistically significant higher risk of progression with respect to patients with <5 CTCs at both blood draws (HR 6.4; 95% CI 2.8-14.6). CONCLUSION: CTCs basal value is a predictive indicator of prognosis and changes in CTC levels during therapy may indicate a clinical response. Testing CTC levels during targeted treatments might substitute other measurement parameters for response evaluation.

Incidence and prevalence of amyotrophic lateral sclerosis in Uruguay: a population-based study.

OBJECTIVE: To determine the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the Republic of Uruguay. METHODS: The study was performed in Uruguay (3,241,003 inhabitants) during a 2-year period (2002-2003). To ensure complete case ascertainment, multiple sources of information were used, including all the neurologists, other medical specialties, general physicians, neurophysiology laboratories, hospital medical records and death certificates. ALS diagnosis was based on El Escorial criteria. Although all patients with motor neuron disease were enrolled in the follow-up, only probable and definite cases are included in the study. RESULTS: Between January 1st, 2002, and December 31st, 2003, 89 new patients were diagnosed with probable or definite ALS. The mean annual incidence rate was 1.37 per 100,000 persons. The incidence was higher for men (1.95) than for women (0.84) with a male to female ratio of 2:1. For both, the incidence increased throughout the years showing a peak in the 65-74 age group among men and the 55-64 age group among women. Mean age at onset of ALS disease was 58.7 years. The estimated mean annual incidence for ALS calculated by the capture recapture method was 1.42 (95% CI, 1.13-1.72). On December 31st, 2002, the crude prevalence was 1.9 per 100,000 inhabitants. CONCLUSIONS: ALS incidence is within a narrow range across countries despite the genetic, environmental and socioeconomic differences when similar prospective design, diagnosis criteria and data analyses are applied.

CT-texture analysis of subsolid nodules for differentiating invasive from in-situ and minimally invasive lung adenocarcinoma subtypes.

PURPOSE: The purpose of this study was to evaluate the usefulness of computed tomography-texture analysis (CTTA) in differentiating between in-situ and minimally-invasive from invasive adenocarcinomas in subsolid lung nodules (SSLNs). MATERIAL AND METHODS: Two radiologists retrospectively reviewed 49 SSLNs in 44 patients. There were 27 men and 17 women with a mean age of 63±7 (SD) years (range: 47-78years). For each SSLN, type (pure ground-glass or part-solid) was assessed by consensus and CTTA was conducted independently by each observer using a filtration-histogram technique. Different filters were used before histogram quantification: no filtration, fine, medium and coarse, followed by histogram quantification using mean intensity, standard deviation (SD), entropy, mean positive pixels (MPP), skewness and kurtosis. RESULTS: We analyzed 13 pure ground-glass and 36 part-solid nodules corresponding to 16 adenocarcinomas in-situ (AIS), 5 minimally invasive adenocarcinomas (MIA) and 28 invasive adenocarcinomas (IVA). At uni- and multivariate analysis CTTA allowed discriminating between IVAs and AIS/MIA (P<0.05 and P=0.025, respectively) with the following histogram parameters: skewness using fine textures and kurtosis using coarse filtration for pure ground-glass nodules, and SD without filtration for part-solid nodules. CONCLUSION: CTTA has the potential to differentiate AIS and MIA from IVA among SSLNs. However, our results require further validation on a larger cohort.

Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia.

The pathogenesis of the immunoglobulin deficiency of 20 patients with ataxia telangiectasia was studied using an in vitro immunoglobulin biosynthesis system. 10 patients had no detectable IgA in their serum as assessed by radial diffusion in agar and 3 had a reduced serum IgA concentration. The peripheral blood mononuclear cells of 17 of the patients and 17 normal controls were cultured with pokeweed mitogen for 12 d and the immunoglobulin in the supernatants measured. The immunoglobulin synthesis was below the lower limit of the normal 95% confidence interval for IgM in 5 patients, for IgG in 8, and for IgA in 14. The mononuclear cells from 9 of the 10 patients with a serum IgA concentration less than 0.1 mg/ml failed to synthesize IgA in vitro. None of the patients manifested excessive suppressor cell activity. All patients had reduced but measurable helper T cell activity for immunoglobulin synthesis by co-cultured normal pokeweed mitogen-stimulated B cells (geometric mean 22% of normal). Furthermore, the addition of normal irradiated T cells to patient peripheral blood mononuclear cells led to an augmentation of IgM synthesis in 15 of 17 and to increased IgG synthesis in 9 of the 17 patients studied, including 9 of the 12 patients who had synthesized IgG before the addition of the irradiated T cells. In addition, IgA synthesis was increased in all eight patients examined that had serum IgA concentrations greater than 0.1 mg/ml. These studies suggest that a helper T cell defect contributes to the diminished immunoglobulin synthesis. However, a helper T cell defect does not appear to be the sole cause since there was no IgA synthesis by the peripheral blood mononuclear cells of 9 of the 10 patients with a profoundly reduced serum IgA even when co-cultured with normal T cells. Furthermore, the cells of the nine patients with profoundly reduced IgA levels examined also failed to produce IgA when stimulated with the relatively helper T cell-independent polyclonal activators, Nocardia water soluble mitogen or Epstein-Barr virus. Taken together these data support the view that the reduced immunoglobulin synthesis of these patients is due to defects of both B cells and helper T cells. Such a broad defect in lymphocyte maturation taken in conjunction with our demonstration of persistent alpha fetoprotein production by ataxia telangiectasia patients provides support for the proposal that these patients exhibit a generalized defect in tissue differentiation.

Optimizing clinical care of patients with metastatic breast cancer: a new oral vinorelbine plus trastuzumab combination.

BACKGROUND: Trastuzumab (T) combined with i.v. vinorelbine (i.v.VNR) is an active regimen for patients with advanced breast cancer (ABC). In order to further improve quality of life of patients undergoing treatment for ABC, a new regimen using oral vinorelbine (oVNR) (d1 + d3) plus q3wks T was tested (ToVNR). PATIENTS AND METHODS: Thirty-nine patients with ABC, human epidermal growth factor receptor 2/neu 3+ or FISH positive received 288 treatment cycles with T 6 mg/kg (loading dose, 8 mg/kg) on d1 and oVNR 55 mg/m(2) on d1 + d3, q3wks until disease progression or unacceptable toxicity. RESULTS: Thirty-seven patients and 286 treatment cycles were evaluated (two patients were lost to follow-up). Treatment was very well tolerated. Two patients had complete response (CR), 14 partial response (PR), 17 stable disease (SD) and four disease progression (PD) (overall response rate: 43%). Clinical benefit rate (CR + PR + SD >24 months) was 73%. Median time to progression was 8.9 months (range 2-27) and median duration of response was 10.9 months (range 2-27). CONCLUSIONS: The ToVNR combination is active and very well tolerated. It favorably compares with the combination of T and weekly i.v. administered VNR, allowing a more convenient once every three weeks hospital admission and leaving patients and care providers free from the unpleasant effect of i.v.VNR.

Signaling pathway used by HSV-1 to induce NF-kappaB activation: possible role of herpes virus entry receptor A.

We have previously demonstrated that wild-type herpes simplex virus type 1 (HSV-1), as well as nonreplicating UV-inactivated HSV-1, promptly activates the nuclear factor-kappaB (NF-kappaB) in U937 monocytoid cells and that glycoprotein D (gD) of HSV-1 is sufficient by itself to exert a similar effect. We then investigated the signaling pathway used by HSV-1 to initiate NF-kappaB activation and, particularly, whether our observation could be related to the capability of HSV-1-gD to directly stimulate NF-kappaB through its interaction with the herpes virus entry receptor A (HveA). Here we report that: (a) co-cultivation of U937 cells with an adherent cell line expressing wild-type gD on its surface led to increased NF-kappaB activation, while co-cultivation with the same adherent cell line expressing a mutated form of gD, lacking the capability to bind HveA, did not cause the same effect; (b) exposure to UV-inactivated HSV-1 induced the activation of NF-kappaB in HveA-expressing U937 and THP-1 cells, but not in non-HveA-expressing HEp-2 cells; and (c) activation of NF-kappaB in U937 and THP-1 cells exposed to soluble gD was inhibited by an antibody able to interfere with gD-HveA interaction. These results suggest that HSV-1-gD-HveA interaction initiates a signal transduction pathway leading to NF-kappaB activation.

Brain metastases in patients with advanced breast cancer.

BACKGROUND: The incidence of brain metastases (BM) is apparently rising in patients with advanced breast cancer (ABC). We performed a case control study to define current features of breast cancer related to central nervous system (CNS) metastases. PATIENTS AND METHODS: From March 1999 to May 2006, we identified 72 patients with symptomatic BM of breast cancer. A comparison group was randomly selected assigning to each case two patients with primary breast cancer and no BM, matched for year of diagnosis, age and tumour stage (pT status and nodal status). RESULTS: Cases had a significantly higher rate of negative estrogen receptors (ERs) (60% in cases vs. 29% in controls), negative progesterone receptors (PgRs) (79% vs. 43%), HER2/neu over expression (44% vs. 13%) and immunostaining for Ki-67 > or =20% (84% vs. 55%), with p-value <0.001 for all four parameters in univariate analyses. On multivariate analysis, HER2/neu over expression and Ki-67 -20% were independent predictive factors of brain relapse (Odds Ratio (OR) 2.55, 95% confidence intervals (CI) 1.10-5.94 and OR 2.97, 95% CI 1.01-8.73, respectively). Endocrine unresponsive tumours (both ER and PgR <10%) showed an increased risk of relapse with BM of borderline significance (OR 1.91, 95% CI 0.87-4.12). CONCLUSION: Patients with ER and PgR negative tumours either with or without HER-2/neu over expression should be considered at higher risk of BM.

Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial.

BACKGROUND: Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator's instruments, meaning the position and progression of the instruments are visualised in real time on the patient's images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. METHODS/DESIGN: This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. DISCUSSION: This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01896219 . Registered on 5 July 2013.