Effectiveness of 2D fingerprints for scaffold hopping.

BACKGROUND: It has been suggested that similarity searching using 2D fingerprints may not be suitable for scaffold hopping. METHODS: This article reports a detailed evaluation of the effectiveness of six common types of 2D fingerprints when they are used for scaffold-hopping similarity searches of the Molecular Design Limited Drug Data Report database, World of Molecular Bioactivity database and Maximum Unbiased Validation database. RESULTS: The results demonstrate that 2D fingerprints can be used for scaffold hopping, with novel scaffolds being identified in nearly every search that was carried out. The degree of enrichment depends on the structural diversity of the actives that are being sought, with the greatest enrichments often being obtained using the extended connectivity fingerprint encoding a circular substructure of diameter four bonds (ECFP4) fingerprint. CONCLUSION: 2D fingerprints provide a simple and computationally efficient way of identifying novel chemotypes in lead-discovery programs.

Tuberculosis complicated by immune reconstitution inflammatory syndrome in a patient on anti-TNFα therapy for Crohn's disease.

A 28-year-old man treated with the antitumour necrosis factor α (TNFα) monoclonal antibody infliximab for Crohn's disease developed pulmonary tuberculosis (TB), despite testing negative for latent TB prior to treatment. On starting anti-TB treatment and withdrawal of the anti-TNFα therapy, he deteriorated both clinically and radiologically. He was diagnosed with a flare of Crohn's disease, and immune reconstitution inflammatory syndrome (IRIS) in his right upper lobe and mediastinal lymph nodes, and commenced on oral prednisolone. Anti-TNFα therapy was re-introduced, and prednisolone weaned, following 4 months of anti-TB treatment without complication. He made a full recovery from TB, although his Crohn's symptoms continue to be troublesome. There has been no reactivation of TB to date, after 2 years follow-up.

Elevated preoperative C-reactive protein predicts poor cancer specific survival in patients undergoing resection for non-small cell lung cancer.

BACKGROUND: Although only the minority of patients with non-small cell lung cancer (NSCLC) are suitable for surgical resection, it offers the best possibility of cure. The aim of this study was to examine the relationship between the clinicopathological status, the preoperative systemic inflammatory response, and survival in patients undergoing potentially curative resection for NSCLC. METHODS: Data from 96 patients who underwent resection of NSCLC between 2000 and 2003 were collected retrospectively and that for 2004-2006 prospectively. RESULTS: All patients had Eastern cooperative oncology group performance status 0 or 1. No patient had T4, unresectable nodal or metastatic disease, and all macroscopic tumors were removed, with subsequent negative surgical margins. The majority of patients were older than 60 years (71%), men (57%), underwent a lobectomy (65%), and had tumor, node, metastasis stage I disease (66%). Of the markers of the systemic inflammatory response, white cell count, C-reactive protein, and albumin, only an elevated C-reactive protein (>10 mg/L) was associated with cancer-specific survival. On multivariate analysis, only tumor, node, metastasis stage (hazard ratio 1.88, 95% confidence interval 1.34-2.63, p < 0.001) and preoperative C-reactive protein (hazard ratio 1.67, 95% confidence interval 1.01-2.83, p < 0.05) retained independent significance. Those patients with a preoperative C-reactive protein concentration >10 mg/L had a median survival of 26.2 months compared with 75.9 months in those patients with a C-reactive protein < or =10 mg/L (p < 0.05). CONCLUSION: The results of this study indicate that the presence of a systemic inflammatory response predicts poor outcome in patients who have undergone potentially curative resection for lung cancer.