Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT -PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I -IV CRC patients with (n ¼ 20) and without (n ¼ 18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of b 2 microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC) ¼ 0.85; 95% confidence interval (CI) ¼ 0.69 -0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC ¼ 0.87; 95% CI ¼ 0.71 -0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R 2 value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival.
Abstract. Colorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative realtime RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12). We were able to determine, by AUC curve analysis, that the ratio of microtubule associated protein 7 (Map7)/B2M was predictive of outcome in our sample set. Further, using Kaplan-Meier survival analysis, we observed significantly different curves as a function of marker positivity for the Map7/B2M (p=0.0001; HR=11) expression ratio. This suggests that the expression ratio of Map7/B2M may serve as a valuable prognostic marker in patients with Stage II colon cancer, and potentially guide therapeutic decision making.
Results 192 prescriptions corresponding to 112 patients were identified. 62 of 112 (56%) were prescribed long-term azithromycin. Bronchiectasis (60%), COPD(19%), asthma (8%), ILD (7%), Bronchiolitis and others (6%) were the variety of diseases for which Azithromycin was prescribed. 28% had pseudomonas colonisation.51(46%) patients were prescribed long-term azithromycin. Of these, 21 (25%) had been on azithromycin for less than 12 months.Sixty eight (82%) patients on long-term azithromycin had had LFTs and 3(3.5%) had audiology testing in the preceding 12 months.21(25%)had documented ECGs with Qtc interval.No patients tested had hearing loss and no documented QTc prolongation.The other common side effect noticed was GI upset in 6 patients (5.6%).The dosing was mostly 250mg three times a week 103(92%) There was also 500mg three times a week in 20(18%) H.influenzae (42%)Staphylococcus aureus (21%)Moraxella catarrhalis (11%)coliform sp (10%). We identified no new NTM in our Cohort. Conclusion Although formal monitoring in this cohort was patchy, Significant documented adverse effects in this cohort were rare and optimal practice for long-term management of azithromycin use remains to be established. Introduction and Objectives Non CF Bronchiectasis has diverse aetiologies. This includes idiopathic, systemic disease related and as a complication of asthma. Such diversity may be important in determining therapeutic strategies (personalised medicines) and may also be an important consideration in clinical trial design. This is increasingly relevant when neutrophil targeting or eosinophil targeted therapies are being developed. We hypothesised that patients could be phenotyped by sputum cytospins irrespective of suspected aetiology or disease severity. Methods Patients underwent a standardised clinical phenotyping protocol including HRCT chest (Anwar et al 2013). Baseline therapy was recorded. Spontaneous sputa were collected in stable state and spirometry was undertaken according to guidelines. Sputum cell counts were calculated using standard methods with data expressed as medians and ranges. P112 DEEPER PHENOTYPING OF NON CF BRONCHIECTASIS THROUGH SPUTUM DIFFERENTIAL COUNTSResults Fifty three patients' data are reported. The M:F ratio was 1:1.4. The mean FEV1 predicted was 62%, mean FEV1/VC ratio was 64%. Forty three (83%) were on inhaled corticosteroids and 24.5% had a historical diagnosis of asthma and /or ABPA. The predominant cell in sputa was neutrophils, median 94 (range 23-100%), macrophages were the 2nd most prevalent cell type median 2.6 (range 0-75%). Eosinophils showed a skewed distribution with median of 0.2 with a range of 0-24.8%. Four patients had sputum eosinophilia >3%. Of these, only 2 had a history of asthma and / or ABPA being diagnosed. Despite historical diagnoses of asthma and / or ABPA in 13 patients the eosinophil percentage was not statistically different to "non asthmatics". (P = 0.59 Chi Sq test) This group included features of ABPA in 2 patients and significant atopy in another.Conclusion...
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