Detection of cutaneous oxygen saturation using a novel snapshot hyperspectral camera: a feasibility study.

BACKGROUND: Tissue necrosis, a consequence of inadequate tissue oxygenation, is a common post-operative complication. As current surgical assessments are often limited to visual and tactile feedback, additional techniques that can aid in the interrogation of tissue viability are needed to improve patient outcomes. In this bi-institutional pilot study, the performance of a novel snapshot hyperspectral imaging camera to detect superficial cutaneous oxygen saturation (StO2) was evaluated. METHODS: Healthy human volunteers were recruited at two participating centers. Cutaneous StO2 of the forearm was determined by a snapshot hyperspectral camera on two separate study days during occlusion-reperfusion of the brachial artery and after induction of local vasodilation. To calculate the blood StO2 at each pixel in the multispectral image, spectra were selected, and fitting was performed over wavelengths ranging from 470 to 950 nm. RESULTS: Quantitative detection of physiological changes in cutaneous StO2 levels was feasible in all sixteen volunteers. A significant (P<0.001) decrease in cutaneous StO2 levels from 78.3% (SD: 15.3) at baseline to 60.6% (SD: 19.8) at the end of occlusion phase was observed, although StO2 levels returned to baseline after five minutes. Mean cutaneous StO2 values were similar in the same subjects on separate study days (Pearson R2: 0.92 and 0.77, respectively) at both centers. Local vasodilation did not yield significant changes in cutaneous StO2 values. CONCLUSIONS: This pilot study demonstrated the feasibility of a snapshot hyperspectral camera for detecting quantitative physiological changes in cutaneous StO2 in normal human volunteers, and serves as a precursor for further validation in perioperative studies.

DNL104, a Centrally Penetrant RIPK1 Inhibitor, Inhibits RIP1 Kinase Phosphorylation in a Randomized Phase I Ascending Dose Study in Healthy Volunteers.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates inflammation, cytokine release, and necroptotic cell death and is implicated in pathogenic cellular pathways in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and multiple sclerosis. Inhibition of RIPK1 activity protects against inflammation and cell death in multiple animal models. DNL104 is a selective, brain-penetrant inhibitor of RIPK1 phosphorylation in clinical development for AD and ALS. DNL104 was tested in 68 healthy volunteers to investigate safety and tolerability, pharmacokinetic profile in plasma and cerebrospinal fluid, and pharmacodynamic effects of RIPK1 inhibition in peripheral blood mononuclear cells in a first-in-human, placebo-controlled, double-blind, randomized single-ascending dose (SAD) and multiple-ascending dose (MAD) study. DNL104 was well-tolerated in the SAD group and during the dosing period of the MAD group. However, postdose liver toxicity in 37.5% of subjects was observed in the MAD, and assessed to be drug related. We demonstrate that DNL104 leads to RIP1 kinase inhibition, and this is not associated with central nervous system (CNS) toxicities, supporting future development of CNS penetrant RIPK1 inhibitors.

Pharmacokinetics of intravenous and inhaled salbutamol and tobramycin: An exploratory study to investigate the potential of exhaled breath condensate as a matrix for pharmacokinetic analysis.

Concentrations of drugs acting in the lungs are difficult to measure, resulting in relatively unknown local pharmacokinetics. The aim of this study is to assess the potential of exhaled breath condensate (EBC) as a matrix for pharmacokinetic analysis of inhaled and intravenous medication. A 4-way crossover study was conducted in 12 volunteers with tobramycin and salbutamol intravenously and via inhalation. EBC and plasma samples were collected postdose and analysed for drug concentrations. Sample dilution, calculated using urea concentrations, was used to estimate the epithelial lining fluid concentration. Salbutamol and tobramycin were largely undetectable in EBC after intravenous administration and were detectable after inhaled administration in all subjects in 50.8 and 51.5% of EBC samples, respectively. Correction of EBC concentrations for sample dilution did not explain the high variability. This high variability of EBC drug concentrations seems to preclude EBC as a matrix for pharmacokinetic analysis of tobramycin and salbutamol.

Recombinant human erythropoietin does not affect several microvascular parameters in well-trained cyclists.

Recombinant human erythropoietin (rHuEPO) has been used as a performance-enhancing agent by athletes in a variety of sports. The resulting increase in hematocrit levels leads to increased blood viscosity and can affect blood flow, potentially increasing the athlete's risk of developing health complications. However, the actual effects of using rHuEPO on microvascular blood flow and post-occlusive reactive hyperemia are currently unknown. We therefore evaluated the effect of rHuEPO on the cutaneous microcirculation in well-trained cyclists using laser speckle contrast imaging (LSCI). This study was part of a randomized, double-blind, placebo-controlled, parallel trial designed to investigate the effects of rHuEPO in 47 well-trained adult cyclists (age 18-50 years). Subjects received a weekly dose of either rHuEPO or placebo for 8 weeks, and LSCI was performed at baseline, after a maximal exercise test in week 6, and before maximal exercise in week 8. Endpoints included basal blood flux, maximum post-occlusion reperfusion, and time to return to baseline. Despite an increase in hematocrit levels in the rHuEPO-treated group, we found no statistically significant difference in microvascular function measured between the rHuEPO-treated group and the placebo group. Our results suggest that the increased hematocrit levels in rHuEPO-treated well-trained cyclists are not associated with changes in microvascular blood flow or post-occlusive reactive hyperemia measured using LSCI.