Search

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease., Competing Interests: The authors declare no conflict of interest.

Introduction: Although laparoscopy has become the standard approach in other procedures, this technique is not generally accepted for acute appendicitis, especially if it is complicated due reports on the increase in intra-abdominal abscesses., Objective: The purpose of this study was to evaluate the morbidity in a group of patients diagnosed with complicated apendicitis (gangrenous or perforated) who had undergone open or laparoscopic appendectomy., Material and Method: We prospectively studied 107 patients who had undergone appendectomy for complicated appendicitis over a two year period. Mean operation time, mean hospital stay and morbidity, such as wound infection and intra-abdominal abscess were evaluated., Results: In the group with gangrenous appendicitis morbidity was significantly lower in laparoscopic appendectomy group (p = 0.014). Wound infection was significantly higher in the open appendectomy group (p = 0.041), and there were no significant differences in intra-abdominal abscesses (p = 0.471). In the perforated appendicitis group overall morbidity (p = 0.046) and wound infection (p = 0.004) was significantly higher in the open appendectomy group. There were no significant differences in intra-abdominal abscesses (p = 0.612)., Conclusion: These results suggest that laparoscopic appendectomy for complicated appendicitis is a safe procedure that may prove to have significant clinical advantages over conventional surgery.

Objective: We analyzed the prognostic factors and evaluated the usefulness of mitotic index to predict the behavior of gastrointestinal stromal tumors (GIST)., Patients and Methods: Fifty three patients operated on for stromal tumors of the digestive tract were studied retrospectively. Mean follow-up was 6 years. The number of mitosis/10 high power fields was the definitive criterion for classification, regardless of their inmunohistologic differentiation. Twelve tumors had 0 mitoses, 34 from 1 to 9 mitoses, and 7 had > or = 10 mitoses. The survival rate was analyzed and the morphological characteristics and evolution were correlated according to mitotic index., Results: The incidence of advanced illness was related to the number of mitoses: 29% in the group with 1 to 9 mitoses, and 86% when there were > or = 10 mitoses. The recurrence intervals were 44 and 8 months respectively. No tumor with 0 mitoses evolved aggressively. The survival rate was significantly related (p < 0.001), to the mitotic index. The group with 0 mitoses had a survival rate of 100% after 10 years, those with 1 to 9 mitoses 69% and those with > or = 10 mitoses 14%. The other factors which influenced the prognosis (location, size, local invasion and resection) depended, as well, on the mitotic index., Conclusion: The classification of digestive tract stromal tumors by mitotic index is an efficient method because it distinguishes 3 entities with different biological behavior in the long term.