Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Biliary sepsis: an ascending infection.

AIM: To study the bacteriology of normal and obstructed biliary tree and determine the mode of biliary infection. METHODS: Fifty seven patients undergoing elective biliary surgery for calculous biliary disease cholecystitis 45, obstructive jaundice 12) were studied. Bile samples collected separately from gall bladder, common bile duct and duodenum at the time of surgery were processed for aerobic and anaerobic cultures and antibiotic assays. To locate endogenous foci of infection, urine, nasal swab and throat swab cultures were done. Isolates from/biliary tract were compared with those from other sites. RESULTS: Thirty eight patients (66.7%) had bactobilia. The prevalence was higher in patients with obstructive jaundice (10/12, 83.3%) than (p = 0.5) in those with non-obstructed biliary tree. Single bacterial infection (31 cases, 81 %) was more common than mixed infection (7 cases, 19%). Colonization of more than one segment of the biliary tree was seen in 30 patients (79%). E coli was the most frequently isolated organism. In 24 cases (63.2%), strains of organisms from the common bile duct and gall bladder were similar to those from the duodenum, and in only 10 cases (23.2%) were similar to those found in the nose, throat and urine. The antibiotic concentrations in the common bile duct after single doses of preoperative antibiotic (gentamicin and cephazolin) were lower in the obstructed biliary tree (1.5 +/- 0.4 milligrams/mL and 2.8 milligrams/mL respectively) than in the non-obstructed system (3.9 +/- 1.7 milligrams and 12.6 milligrams/mL/mL respectively) (p = 0.5 for both antibiotics). CONCLUSION: Ascending infection forms the mode of biliary sepsis in a majority of cases. Prophylactic antibiotics give low levels in the bile in an obstructed biliary tree.