Escherichia coli K-12 acquired the ability to produce a high titer of Shiga-like toxin after lysogenization by either of two different bacteriophages isolated from a highly toxinogenic Escherichia coli O157:H7 strain that causes hemorrhagic colitis. One of these phages and another Shiga-like toxin-converting phage from an Escherichia coli O26 isolate associated with infantile diarrhea were closely related in terms of morphology, virion polypeptides, DNA restriction fragments, lysogenic immunity, and heat stability, although a difference in host range was noted. These phages are currently the best-characterized representatives from a broader family of Shiga-like toxin-converting phages.

SummaryThe HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term “HGG” in the pediatric population.

) S U M M A R YMost invasive strains of Escherichia coli from man and domestic animals were lethal for chickens and mice. The lethal characteristic was not, in general, transferred when invasive strains were grown in mixed culture with non-pathogenic strains of E. coli, although two transmissible plasmids coding for pathogenic properties were discovered.One plasmid, designated Vir, was found in an E. coli strain causing bacteraemia in a lamb. It transferred at high rate to several strains of E. coli, including a rec A-KI 2 strain, to Salmonella typhi, Salm. typhimuriunz and Shigella sonnei. Culture filtrates and, especially, bacterial ultrasonicates of Vir+ strains were toxic for chickens, mice and rabbits. The toxin was heat-sensitive, acid-sensitive and non-diffusible. Organisms producing it were agglutinated by specific Vir+ antisera; their toxic activity was not neutralized. The transfer factor of the Vir plasmid was fi+ and could transfer antibiotic-resistance determinants in addition to the Vir determinant.The other plasmid was first discovered in an E. coli strain ~1 2 0 , isolated from an outbreak of bacteraemia in chickens. Organisms of E. coli K I~ and of other E. coli strains acquiring this plasmid during mixed culture with ~1 2 0 were increased in lethality for chickens and mice; this was associated not with toxic activity but with greater ability to survive in blood and peritoneal fluids. Strain F I 20 possessed transmissible ColV and Col Ib plasmids; increased lethality was closely associated with the ColV plasmid. When the ColV plasmids of another six wild strains of E. coli of varied origin were transferred to organisms of E. coh K 1 2 , the lethality increase was similar to that for ColV transfer from ~1 2 0 . No lethality change accompanied transfer of other Col plasmids. It was concluded that colicine V itself might be responsible for the increased lethality.Strains of E. coli associated with bacteraemia in man and animals commonly produced colicine V.

Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m per day, days 1 to 5; cycles 2 to 12: 200 mg/m per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee-assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.