Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed.

Absorption is a widely used technique for a range of different applications. It has lower sensitivity than many other techniques such as fluorescence which has 100 to 1000 times higher sensitivity than absorption. Optical cavity approaches have been developed where the light passes back and forth, within the sample, between two high reflectivity mirrors to increase the pathlength and sensitivity. These approaches have not yet, however, been widely used for analytical applications and for point-of-care diagnostics. Here we show a portable cavity enhanced absorption (CEA) spectrometer and a low cost point-of-care (POC) reader with CEA detection with mechanical elements fabricated using 3D printing. The CEA spectrometer can be used in both single pass and multi-pass cavity enhanced mode to provide measurements in the visible region that are very sensitive and over a wide dynamic range. The CEA mode was shown for Rhodamine B dye to increase the pathlength 57.8 fold over single pass measurements and an LOD of 7.1 × 10⁻¹¹ M. The cost of the CEA POC reader was reduced by use of narrow band LEDs, photodiodes and removal of fibre optic coupling and with a 14 fold increase in the pathlength over conventional single pass microplate readers. The CEA POC reader was demonstrated for immunoassay of C-Reactive Protein (CRP), Procalcitonin (PCT) and Interleukin 6 (IL-6), towards a three biomarker panel to aid the diagnosis of sepsis. The CEA POC reader can be integrated with wireless connectivity for cloud based data sharing. We show here the potential for the wider use of optical cavity approaches where there is a need for sensitive absorption measurements and also for low cost point-of-care diagnostics.

We queried whether adrenal insufficiency attributable to non‐classic congenital adrenal hyperplasia (21 hydroxylase deficiency, 21OHD) might contribute to heat illness susceptibility. Patients referred to a specialist heat illness clinic (n = 2 with prior hyponatremia; n = 16 lacking documentary evidence) and controls (n = 16) underwent laboratory Heat Tolerance Assessment (HTA: 60–90 min walking, 60% relative intensity, 34°C heat), synthetic adrenocorticotrophic hormone stimulation (heat illness only) and CYP21A2 genotyping (hyponatremic heat illness only). Copeptin, cortisol, 17‐hydroxyprogesterone, and 21 deoxycortisol were assayed from blood at baseline and post‐HTA, with precursor product [17‐hydroxyprogesterone +21 deoxycortisol] expressed relative to cortisol. Saliva and urine were assayed for free cortisol (one hyponatremic case, controls). Versus controls, normonatremic heat illness exhibited greater (p < 0.05) serum cortisol across HTA, while hyponatremic heat illness showed blunted responses in aldosterone and free cortisol (salivary cortisol 1.6 and 1.6 vs. 6.0 [4.2, 19.4] and 4.2 [3.8, 19.2] nmol.L‐1; urine cortisol 19 vs. 117 +/− 71 nmol.L‐1). Hyponatremic heat illness demonstrated elevated precursor product consistent with 21OHD and multiple CYP21A2 mutations. One normonatremic case of heat illness also showed elevated precursor product. These data support the potential for 21OHD to precipitate heat illness under sustained physical stress and advance a case for targeted genetic screening.