Metformin inhibits cancer cell proliferation and epidemiology studies suggest an association with increased survival in cancer patients taking metformin, however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation while increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.

Study Type – Therapy (case series)
Level of Evidence 4 OBJECTIVE To assess how advances in urology, radiology and orthopaedics are changing the current management of bladder ruptures, by reviewing patients treated for bladder ruptures after blunt trauma. PATIENTS AND METHODS Our database was screened for patients admitted with bladder ruptures between 1980 and 2008. Charts were reviewed for demographics, clinical variables, diagnostics, treatment and outcome. RESULTS Thirty‐six patients with extraperitoneal (EPR, 61%) and intraperitoneal (IPR) or combined ruptures (39%) were identified; 81% of them presented pelvic‐ring fractures. Diagnosis relied on computed tomography cystography (CT‐C), which has replaced plain‐film cystography. The sensitivity of either type of cystography was >90%. However, three bladder ruptures (11%) were missed on CT‐C performed with insufficient bladder distension. All 14 patients with IPRs had immediate surgical repair, four of them by laparoscopy. Twelve of 22 EPRs (55%) were sutured during concomitant orthopaedic/visceral surgery or because of the urologist’s apprehension of infection. Only eight of 22 patients with EPR (36%) completed conservative treatment. CONCLUSIONS Diagnosis relies increasingly on CT‐C, allowing simultaneous assessment of multiple organ systems. However, only specific CT‐C guarantees an adequate sensitivity. Orthopaedists increasingly use open reductions and fixation of pelvic‐ring fractures, prompting urologists to suture EPRs simultaneously. Our data indicate that this proactive management reduces infectious complications, and we have adopted it as the standard of care in our institution. Laparoscopic suture is an advantageous treatment of isolated IPR.

E. Forestier). y Forestier Emmanuel and Claire Roubaud-Baudron are joint first authors.x The members of the collab group AEPEI and the GInGer Elderl-IE study group are listed under the Acknowledgements section. Contents lists available at ScienceDirect Clinical Microbiology and Infectionj o u r n a l h o m e p a g e : w w w . c l i n i c a l m i c r o b i o l o g y a n d i n f e c t i o n . c o m

BackgroundNontuberculous mycobacteria (NTM) are environmental organisms associated with a range of infections. Reports of NTM epidemiology are mainly focused on pulmonary infections and isolations, and extrapulmonary infections are less frequently described.MethodsWe conducted a retrospective study of NTM infections at the Bordeaux University Hospital, France, between January 2002 and December 2013. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease.ResultsIn our setting, 170 patients were included. Pulmonary cases predominated (54.1%), followed by skin and soft tissue infections (22.9%), disseminated cases (10.6%), lymphadenitis (7.7%), bone and joint infections (2.9%) and the remaining 1.8% catheter-related infections. Overall, 16 NTM species were isolated. Mycobacterium avium (31.8%) and M. intracellulare (20%) were the most common species identified, followed by M. marinum (13.5%), M. kansasii (10.6%), M. xenopi (9.4%), rapidly growing mycobacteria (9.4%) and other slowly growing mycobacteria (5.3%). In general, NTM isolates were largely prevalent in people older than 50 (62.4%); patients aged 1–10 year-old exclusively yielded M. avium from lymph nodes, almost cases having being diagnosed after 2007. Among the 121 patients with complete follow-up, 78 (64.5%), 24 (19.8%), and 19 (15.7%) were cured, experienced relapse, or died, respectively.ConclusionIn our study, extrapulmonary NTM infections represented almost half of cases, consisting mainly in skin and soft tissue infections. The increase lymphadenitis cases in children after 2007 could be linked to the cessation of mandatory BCG vaccination in France. We observed similar cure rates (64%) between pulmonary and extrapulmonary infections.

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