Archive for May 11, 2017

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring.

Proc Natl Acad Sci USA. Apr 11, 2017 V.114 N.15 P.3969-3974.

Liu C1,2,3, Zhao Z4, Fan J1,3, Lyon CJ1,3, Wu HJ1,5, Nedelkov D6, Zelazny AM4, Olivier KN7, Cazares LH8, Holland SM9, Graviss EA10, Hu Y11,2,3.

Author information

1 Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030.

2 School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287.

3 Virginia G. Piper Biodesign Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.

4 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892.

5 Department of Chemical Engineering, Texas A&M University, College Station, TX 77843.

6 Molecular Biomarkers Laboratory, The Biodesign Institute, Arizona State University, Tempe, AZ 85287.

7 Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.

8 Molecular and Translational Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702.

9 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

10 Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.

11 Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030; tyhu@asu.edu.

Abstract

Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393254/pdf/pnas.201621360.pdf

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May 11, 2017 at 11:28 am

Powassan Virus Disease in an Infant – Connecticut, 2016.

MMWR Morb Mortal Wkly Rep. Apr 21, 2017 V.66 N.15 P.408-409.

Notes from the Field:

Tutolo JW, Staples JE, Sosa L, Bennett N.

PDF

https://www.cdc.gov/mmwr/volumes/66/wr/pdfs/mm6615a3.pdf

May 11, 2017 at 11:20 am

Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis

N Engl J Med  Mar 21, 2017

The PRISM Investigators*

BACKGROUND

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.

METHODS

We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics.

RESULTS

We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.

CONCLUSIONS

In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1701380

May 11, 2017 at 11:13 am


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