SummaryBackgroundData suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival.MethodsFOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global).FindingsBetween Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least ...

A direct comparison of two automated blood culture systems was conducted to compare their ability to detect Candida growth. The systems evaluated were the BACTEC 9240 (Bactec) and BacT/ALERT 3D (BacT). The aerobic, anaerobic, and mycology media for each system were evaluated: Bactec Plus Aerobic/F, Plus Anaerobic/F, and Myco/F Lytic bottles,, respectively, and BacT FA, SN, and MB bottles, respectively. Each blood culture bottle was inoculated with fresh blood from healthy donors. Fifty isolates of Candida spp. were used. The six different blood culture bottles were each inoculated with 1,000 yeasts per bottle and then incubated in the corresponding automated system. The BacT detected growth of 90% (135 of 150) of Candida pathogens, while Bactec detected 66% (100 of 150). Growth was detected in all BacT and Bactec mycology bottles, all BacT aerobic bottles, and by terminal subculture of all bottles. Sixty-five of 300 (22%) bottles had no growth detected; 50 from the Bactec (5 aerobic and 45 anaerobic) and 15 from the BacT (all anaerobic). Terminal subculture of "negative" bottles demonstrated viable yeast growth from all 65 bottles, representing 65 false-negatives. The mean time to growth detection in the BacT system was 25.62 h while the Bactec was 27.30 h (P < 0.01). Both automated blood culture systems detected all episodes of simulated candidemia when specialized mycology media were used. However, when only standard aerobic and anaerobic media were used, the BacT performed better than the Bactec in overall growth detection, time to growth detection, and number of false-negatives.Candida spp. are now the fourth most common pathogen isolated from the blood of hospitalized patients in the United States (5, 19). Unfortunately, candidemia is also associated with the highest mortality (40%) of all nosocomial bloodstream infections (5). Episodes of candidemia are most commonly detected with standard aerobic and anaerobic blood culture media in automated blood culture systems. Multiple studies have demonstrated effective recovery of Candida spp. with the BACTEC 9240 (Bactec) (BD Diagnostic Systems, Sparks, Md.) (7,18,20,27) and BacT/ALERT 3D (BacT) (bioMérieux, Inc., Durham, N.C.) (3,4,6,8,13,24,28) automated blood culture systems. Several studies also exist that compare the BacT and Bactec automated blood culture systems (10,12,14,17,21,23,26,29). However, these studies address only a small number of candidemia episodes, primarily secondary to Candida albicans. The predominant cause of candidemia had been C. albicans until recently (1), but now Candida species other than C. albicans, collectively termed "nonalbicans Candida" (NAC), species, particularly Candida glabrata, Candida parapsilosis, and Candida tropicalis, account for approximately one-half of all nosocomial bloodstream Candida isolates recovered from patients in the United States (5,11,16,19,25).The ability of automated blood culture systems to detect growth of NAC species has not been thoroughly evaluated.The growth requirements and characteristics may b...

Candidemia was simulated with 15 Candida spp. by using an automated blood culture system. Candida growth was detected in 479/648 (74%) bottles: 211/216 (98%) aerobic bottles, 58/216 (27%) anaerobic bottles, and 210/216 (97%) mycology bottles. Only the growth of Candida lipolytica failed to be detected in all media.

A 65-year-old female patient with glioblastoma multiforme (GBM) developed aplastic anemia following treatment with temozolomide. Following her diagnosis of GBM, the patient received standard treatment with surgery, concomitant radiation therapy and temozolomide followed by adjuvant temozolomide. On day 14 of her adjuvant treatment, she developed profound fatigue and spontaneous bruising and was noted to be severely pancytopenic. After an extensive workup, she was found to have aplastic anemia on bone marrow bipsy. Further studies did not reveal any other etiology and she was not on any other medications known to cause aplastic anemia. There have been two previously published cases involving aplastic anemia due to temozolomide. This case represents a rare but potentially fatal toxicity from temozolomide.