Interrater reliability of chart-based assessment of functional impairment after pediatric injury using the functional status scale.

BACKGROUND: Functional impairment has been proposed as an alternative outcome for quality improvement in pediatric trauma. The functional status scale (FSS) has been used in studies of injured children, but has only been validated with resource-intensive in-person assessment. Implementation with retrospective chart-based FSS assessment would offer a simplified and scalable alternative. The purpose of this study was to evaluate interrater reliability of retrospective FSS assessment and to identify factors associated with unreliable assessment. METHODS: A retrospective cohort of admissions to a Level I pediatric trauma center between July 2020 and June 2021 was analyzed. Two physicians and two nurse registrars reviewed charts to obtain measures of six FSS domains (mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status) at discharge. Functional impairment was categorized by total FSS scores as good (6,7), mild impairment (8,9), moderate impairment (10-15), severe impairment (16-21), or very severe impairment (>21). Interrater reliability was assessed using intraclass correlation (ICC). Predictors of rater disagreement were evaluated using multivariable logistic regression. RESULTS: The cohort included 443 children with a mean age of 7.4 years (standard deviation, 5.4 years) and median Injury Severity Score of 9 (interquartile range, 5-12). The median time per chart to assess FSS was 2 minutes (interquartile range, 1-2). Thirty-seven patients (8%) had functional impairment at discharge. Interrater reliability was excellent for total FSS score (ICC = 0.87) and good for FSS impairment categorization (ICC = 0.80). Rater disagreement of functional impairment categorization occurred in 14% of cases overall. Higher level of functional impairment and use of therapies (occupational and speech language therapy) were independently associated with more frequent rater disagreement. CONCLUSION: Chart-based FSS assessment is feasible and reliable, but may require more detailed review for patients with higher level of impairment that require allied health therapy. Validation of chart-based assessment is needed before widespread implementation. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.

We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.

Dendritic cells pulsed with a recombinant chlamydial major outer membrane protein antigen elicit a CD4(+) type 2 rather than type 1 immune response that is not protective.

Chlamydia trachomatis is an obligate intracellular bacterium that infects the oculogenital mucosae. C. trachomatis infection of the eye causes trachoma, the leading cause of preventable blindness. Infections of the genital mucosae are a leading cause of sexually transmitted diseases. A vaccine to prevent chlamydial infection is needed but has proven difficult to produce by using conventional vaccination approaches. Potent immunity to vaginal rechallenge in a murine model of chlamydial genital infection has been achieved only by infection or by immunization with dendritic cells (DC) pulsed ex vivo with whole inactivated organisms. Immunity generated by infection or ex vivo antigen-pulsed DC correlates with a chlamydia-specific interleukin 12 (IL-12)-dependent CD4(+) Th1 immune response. Because of the potent antichlamydial immunizing properties of DC, we hypothesized that DC could be a powerful vehicle for the delivery of individual chlamydial antigens that are thought to be targets for more conventional vaccine approaches. Here, we investigated the recombinant chlamydial major outer membrane protein (rMOMP) as a target antigen. The results demonstrate that DC pulsed with rMOMP secrete IL-12 and stimulate infection-sensitized CD4(+) T cells to proliferate and secrete gamma interferon. These immunological properties implied that rMOMP-pulsed DC would be potent inducers of MOMP-specific CD4(+) Th1 immunity in vivo; however, we observed the opposite result. DC pulsed ex vivo with rMOMP and adoptively transferred to naive mice generated a Th2 rather than a Th1 anti-MOMP immune response, and immunized mice were not protected following infectious challenge. We conclude from these studies that the immunological properties of ex vivo pulsed DC are not necessarily predictive of the immune response generated in vivo following adoptive transfer. These findings suggest that the nature of the antigen used to pulse DC ex vivo influences the Th1-Th2 balance of the immune response in vivo.