RESUMEN
Background: In operating room (OR) surfaces, Nosocomial pathogens can persist on inanimate surfaces for long intervals and are highly resistant to traditional surface cleaning. Aim: This study compares traditional chemical operating room terminal disinfection to a unique operator-driven device that emits germicidal UV light at short distance onto vertical and horizontal surfaces. Methods: A randomized crossover analogous protocol assigned 40 end-of-day operating rooms into either group A (chemical then UVC treatments) or group B (UVC then chemical treatments). Initial Staphylococcal cultures were obtained prior to disinfection treatment, after the first treatment, and after the second treatment at 16 most commonly contaminated sites to represent overall room contamination. Success was defined as no growth and failure as 1 or more colony forming units. Thoroughness of chemical treatment vs UVC treatment was compared and used to determine if the second treatment was additive to the first treatment within each group. Findings: The operator driven UVC device outperformed chemical treatment in reducing the number of contaminated sites in the OR by more than half (P<0.001). Operator-driven UVC reduced contaminated sites after chemical treatment by nearly half (P<0.001). In contrast, chemical treatment after operator-driven UVC did not significantly reduce the number of contaminated sites. The mean employee time of disinfection for chemical treatment was 49 minutes and for the operator-driven UVC emitter 7.9 minutes (P<0.001). Conclusions: This study demonstrates that addition of an operator-driven UVC emitter to OR rooms between cases could be helpful in overall decreasing the number of contaminated sites.
RESUMEN
Targeted therapy development in head and neck squamous cell carcinoma (HNSCC) is challenging given the rarity of activating mutations. Additionally, HNSCC incidence is increasing related to human papillomavirus (HPV). We sought to develop an in vivo model derived from patients reflecting the evolving HNSCC epidemiologic landscape, and use it to identify new therapies. Primary and relapsed tumors from HNSCC patients, both HPV+ and HPV-, were implanted on mice, giving rise to 25 strains. Resulting xenografts were characterized by detecting key mutations, measuring protein expression by IHC and gene expression/pathway analysis by mRNA-sequencing. Drug efficacy studies were run with representative xenografts using the approved drug cetuximab as well as the new PI3K inhibitor PX-866. Tumors maintained their original morphology, genetic profiles and drug susceptibilities through serial passaging. The genetic makeup of these tumors was consistent with known frequencies of TP53, PI3KCA, NOTCH1 and NOTCH2 mutations. Because the EGFR inhibitor cetuximab is a standard HNSCC therapy, we tested its efficacy and observed a wide spectrum of efficacy. Cetuximab-resistant strains had higher PI3K/Akt pathway gene expression and protein activation than cetuximab-sensitive strains. The PI3K inhibitor PX-866 had anti-tumor efficacy in HNSCC models with PIK3CA alterations. Finally, PI3K inhibition was effective in two cases with NOTCH1 inactivating mutations. In summary, we have developed an HNSCC model covering its clinical spectrum whose major genetic alterations and susceptibility to anticancer agents represent contemporary HNSCC. This model enables to prospectively test therapeutic-oriented hypotheses leading to personalized medicine.
