Sepsis biomarkers and diagnostic tools with a focus on machine learning.

Over the last years, there have been advances in the use of data-driven techniques to improve the definition, early recognition, subtypes characterisation, prognostication and treatment personalisation of sepsis. Some of those involve the discovery or evaluation of biomarkers or digital signatures of sepsis or sepsis sub-phenotypes. It is hoped that their identification may improve timeliness and accuracy of diagnosis, suggest physiological pathways and therapeutic targets, inform targeted recruitment into clinical trials, and optimise clinical management. Given the complexities of the sepsis response, panels of biomarkers or models combining biomarkers and clinical data are necessary, as well as specific data analysis methods, which broadly fall under the scope of machine learning. This narrative review gives a brief overview of the main machine learning techniques (mainly in the realms of supervised and unsupervised methods) and published applications that have been used to create sepsis diagnostic tools and identify biomarkers.

Use of amplicon melt temperature to detect SARS-CoV-2 Lineage B.1.1.7 variant through the G28048T mutation in the ORF 8 gene.

A new variant of SARS-CoV-2 (Lineage B.1.1.7) was identified in the UK in December 2020 which was associated with higher transmissibility of COVID-19. The AusDiagnostics SARS-CoV-2, Influenza and RSV 8-well assay is used at sixteen UK hospitals and detects part of the ORF8 gene (together with a segment from the ORF1a gene). The objective of this study was to determine if the recently identified mutation in ORF8 (G28048T) in the B.1.1.7. lineage could be used to identify the new variant quickly in clinical cases with PCR positive results. The melt data from SARS-CoV-2 positives from two hospitals (October through December 2020) were reviewed, and distribution over time and location was evaluated. A low melt variant of the ORF8 amplicon started to appear in samples from Guy's and St. Thomas' NHS Trust, London, at the start of November, and grew as a proportion of the total positives during the subsequent two months. These low melt variants were very rare during the same period at the Northern Care Alliance, Greater Manchester, North West of UK. It was confirmed that these carried the G28048T mutation. The geographic and temporal distribution of the low melt amplicons makes it very likely that these are lineage B.1.1.7 strains. The melt temperature of this amplicon could be used to discriminate between the original and new variants in advance of the full sequencing of the isolate. However, the appearance of other mutations in the same amplicon means that this approach would be of diminishing value over time.

Early Mobilization After Stroke Is Not Associated With Cognitive Outcome.

Background and Purpose- We aimed to determine whether early mobilization after stroke affects subsequent cognitive function. Methods- AVERT (A Very Early Rehabilitation Trial) was an international, 56-site, phase 3 randomized controlled trial, conducted from 2006 to 2015. Participants were included if they were aged 18+, presented within 24 hours of stroke, and satisfied physiological limits for blood pressure, heart rate, and temperature. Participants were randomized to receive either usual stroke unit care or very early and more frequent mobilization in addition to usual stroke unit care. The Montreal Cognitive Assessment, scored 0 to 30, was introduced as a 3-month outcome during 2008. Results- Of the 2104 patients included in AVERT, 317 were assessed before the Montreal Cognitive Assessment's introduction. Of the remaining 1787, 1189 (66.5%) had complete Montreal Cognitive Assessment data, 456 (25.5%) had partially or completely missing data, 136 (7.6%) had died, and 6 (0.3%) were lost to follow-up. In surviving participants with complete data, adjusting for age and stroke severity, total Montreal Cognitive Assessment score was no different in the intervention (n=595; median, 23; interquartile range, 19-26; mean, 21.9; SD, 5.9) and usual care (n=594; median, 23; interquartile range, 19-26; mean, 21.8; SD, 5.9) groups ( P=0.68). Conclusions- Exposure to earlier and more frequent mobilization in the acute stage of stroke does not influence cognitive outcome at 3 months. This stands in contrast to the primary outcome from AVERT (modified Rankin Scale), where the intervention group had less favorable outcomes than controls. Clinical Trial Registration- URL: https://www.anzctr.org.au . Unique identifier: ACTRN12606000185561.