Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit.
2021; 11 (1): 13062
Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested prospective validation of an 11-gene messenger RNA (mRNA) score in an ICU population. Whole blood mRNA from 70 subjects in the Stanford ICU Biobank with samples collected within 24h of Emergency Department presentation were used to calculate an 11-gene mRNA score. We found that the 11-gene score was highly associated with 60-day mortality, with an area under the receiver operating characteristic curve of 0.68 in all patients, 0.77 in shock patients, and 0.98 in patients whose primary determinant of prognosis was acute illness. Subjects with the highest quartile of mRNA scores were more likely to die in hospital (40% vs 7%, p<0.01) and within 60days (40% vs 15%, p=0.06). The 11-gene score improved prognostication with a categorical Net Reclassification Improvement index of 0.37 (p=0.03) and an Integrated Discrimination Improvement index of 0.07 (p=0.02) when combined with Simplified Acute Physiology Score 3 or Acute Physiology and Chronic Health Evaluation II score. The test performed poorly in the 95 independent samples collected>24h after emergency department presentation. Tests will target a 30-min turnaround time, allowing for rapid results early in admission. Moving forward, this test may provide valuable real-time prognostic information to improve triage decisions and allow for enrichment of clinical trials.
View details for DOI 10.1038/s41598-021-91201-7
View details for PubMedID 34158514
A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections.
2020; 11 (1): 1177
Improved identification of bacterial and viral infections would reduce morbidity from sepsis, reduce antibiotic overuse, and lower healthcare costs. Here, we develop a generalizable host-gene-expression-based classifier for acute bacterial and viral infections. We use training data (N=1069) from 18 retrospective transcriptomic studies. Using only 29 preselected host mRNAs, we train a neural-network classifier with a bacterial-vs-other area under the receiver-operating characteristic curve (AUROC) 0.92 (95% CI 0.90-0.93) and a viral-vs-other AUROC 0.92 (95% CI 0.90-0.93). We then apply this classifier, inflammatix-bacterial-viral-noninfected-version 1(IMX-BVN-1), without retraining, to an independent cohort (N=163). In this cohort, IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.86 (95% CI 0.77-0.93), and viral-vs.-other 0.85 (95% CI 0.76-0.93). In patients enrolled within 36h of hospital admission (N=70), IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.92 (95% CI 0.83-0.99), and viral-vs.-other 0.91 (95% CI 0.82-0.98). With further study, IMX-BVN-1 could provide a tool for assessing patients with suspected infection and sepsis at hospital admission.
View details for DOI 10.1038/s41467-020-14975-w
View details for PubMedID 32132525
Cat scratch disease: U.S. clinicians' experience and knowledge.
Zoonoses and public health
2018; 65 (1): 67–73
Cat scratch disease (CSD) is a zoonotic infection caused primarily by the bacterium Bartonella henselae. An estimated 12,000 outpatients and 500 inpatients are diagnosed with CSD annually, yet little is known regarding clinician experience with and treatment of CSD in the United States. Questions assessing clinical burden, treatment and prevention of CSD were posed to 3,011 primary care providers (family practitioners, internists, paediatricians and nurse practitioners) during 2014-2015 as part of the annual nationwide DocStyles survey. Among the clinicians surveyed, 37.2% indicated that they had diagnosed at least one patient with CSD in the prior year. Clinicians in the Pacific and Southern regions were more likely to have diagnosed CSD, as were clinicians who saw paediatric patients, regardless of specialty. When presented with a question regarding treatment of uncomplicated CSD, only 12.5% of clinicians chose the recommended treatment option of analgesics and monitoring, while 71.4% selected antibiotics and 13.4% selected lymph node aspiration. In a scenario concerning CSD prevention in immunosuppressed patients, 80.6% of clinicians chose some form of precaution, but less than one-third chose the recommended option of counseling patients to treat their cats for fleas and avoid rough play with their cats. Results from this study indicate that a substantial proportion of U.S. clinicians have diagnosed CSD within the past year. Although published guidelines exist for treatment and prevention of CSD, these findings suggest that knowledge gaps remain. Therefore, targeted educational efforts about CSD may benefit primary care providers.
View details for DOI 10.1111/zph.12368
View details for PubMedID 28707827
Current Guidelines, Common Clinical Pitfalls, and Future Directions for. Laboratory Diagnosis of Lyme Disease, United States
EMERGING INFECTIOUS DISEASES
2016; 22 (7): 1169–77
In the United States, Lyme disease is caused by Borrelia burgdorferi and transmitted to humans by blacklegged ticks. Patients with an erythema migrans lesion and epidemiologic risk can receive a diagnosis without laboratory testing. For all other patients, laboratory testing is necessary to confirm the diagnosis, but proper interpretation depends on symptoms and timing of illness. The recommended laboratory test in the United States is 2-tiered serologic analysis consisting of an enzyme-linked immunoassay or immunofluorescence assay, followed by reflexive immunoblotting. Sensitivity of 2-tiered testing is low (30%-40%) during early infection while the antibody response is developing (window period). For disseminated Lyme disease, sensitivity is 70%-100%. Specificity is high (>95%) during all stages of disease. Use of other diagnostic tests for Lyme disease is limited. We review the rationale behind current US testing guidelines, appropriate use and interpretation of tests, and recent developments in Lyme disease diagnostics.
View details for DOI 10.3201/eid2207.151694
View details for Web of Science ID 000378563900004
View details for PubMedID 27314832
View details for PubMedCentralID PMC4918152