OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING: Four U.S. emergency departments. PATIENTS: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS: Forty-five–transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes. MEASUREMENTS AND MAIN RESULTS: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84–0.94) and 0.92 (95% CI, 0.87–0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78–0.90) for bacterial infection and 0.91 (95% CI, 0.85–0.94) for viral infection. The test had 80.1% (95% CI, 73.7–85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8–90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4–75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.

The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40 years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters. Sixteen poly(lactic-co-glycolic acid) (PLGA) microsphere formulations containing bovine serum albumin (BSA) as a model vaccine antigen were screened in vitro to determine their respective release kinetics. Three formulations that exhibited desirable pulsatile release profiles were then selected for studying immunogenicity in mice. Two low-dose microsphere formulations induced peak anti-BSA IgG antibody titers of 13.9 ± 1.3 and 13.7 ± 2.2 log2 compared to 15.5 ± 1.5 log2 for a series of three bolus injections delivered at 0, 4, and 8 weeks with an equivalent cumulative dose. Similarly, high-dose formulations induced peak antibody titers that were 16.1 ± 2.1 log2 compared to 17.7 ± 2.2 log2 for controls. All three microparticle formulations studied in vivo induced peak antibody titers that were statistically similar to bolus controls. These results suggest that pulsatile antigen release from polymeric microparticles is a promising approach for single-injection vaccination, which could potentially reduce the logistical burden associated with immunization in the developing world.

BackgroundDistinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases.MethodsSubjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin.Findings151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85–0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02).InterpretationThe RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.

OBJECTIVEDepression is the most prevalent affective disorder in the US, and patients with spinal deformity are at increased risk. Postoperative delirium has been associated with inferior surgical outcomes, including morbidity and mortality. The relationship between depression and postoperative delirium in patients undergoing spine surgery is relatively unknown. The aim of this study was to determine if depression is an independent risk factor for the development of postoperative delirium in patients undergoing decompression and fusion for deformity.METHODSThe medical records of 923 adult patients (age ≥ 18 years) undergoing elective spine surgery at a single major academic institution from 2005 through 2015 were reviewed. Of these patients, 255 (27.6%) patients had been diagnosed with depression by a board-certified psychiatrist and constituted the Depression group; the remaining 668 patients constituted the No-Depression group. Patient demographics, comorbidities, and intra- and postoperative complication rates were collected for each patient and compared between groups. The primary outcome investigated in this study was rate of postoperative delirium, according to DSM-V criteria, during initial hospital stay after surgery. The association between depression and postoperative delirium rate was assessed via multivariate logistic regression analysis.RESULTSPatient demographics and comorbidities other than depression were similar in the 2 groups. In the Depression group, 85.1% of the patients were taking an antidepressant prior to surgery. There were no significant between-group differences in intraoperative variables and rates of complications other than delirium. Postoperative complication rates were also similar between the cohorts, including rates of urinary tract infection, fever, deep and superficial surgical site infection, pulmonary embolism, deep vein thrombosis, urinary retention, and proportion of patients transferred to the intensive care unit. In total, 66 patients (7.15%) had an episode of postoperative delirium, with depressed patients experiencing approximately a 2-fold higher rate of delirium (10.59% vs 5.84%). In a multivariate logistic regression analysis, depression was an independent predictor of postoperative delirium after spine surgery in spinal deformity patients (p = 0.01).CONCLUSIONSThe results of this study suggest that depression is an independent risk factor for postoperative delirium after elective spine surgery. Further studies are necessary to understand the effects of affective disorders on postoperative delirium, in hopes to better identify patients at risk.