DCE-CT parameters as new functional imaging biomarkers at baseline and during immune checkpoint inhibitor therapy in patients with lung cancer - a feasibility study.

BACKGROUND: With the development of immune checkpoint inhibitors for the treatment of non-small cell lung cancer, the need for new functional imaging techniques and early response assessments has increased to account for new response patterns and the high cost of treatment. The present study was designed to assess the prognostic impact of dynamic contrast-enhanced computed tomography (DCE-CT) on survival outcomes in non-small cell lung cancer patients treated with immune checkpoint inhibitors. METHODS: Thirty-three patients with inoperable non-small-cell lung cancer treated with immune checkpoint inhibitors were prospectively enrolled for DCE-CT as part of their follow-up. A single target lesion at baseline and subsequent follow-up examinations were enclosed in the DCE-CT. Blood volume deconvolution (BVdecon), blood flow deconvolution (BFdecon), blood flow maximum slope (BFMax slope) and permeability were assessed using overall survival (OS) and progression-free survival (PFS) as endpoints in Kaplan Meier and Cox regression analyses. RESULTS: High baseline Blood Volume (BVdecon) (> 12.97 ml × 100 g-1) was associated with a favorable OS (26.7 vs 7.9 months; p = 0.050) and PFS (14.6 vs 2.5 months; p = 0.050). At early follow-up on day seven a higher relative increase in BFdecon (> 24.50% for OS and > 12.04% for PFS) was associated with an unfavorable OS (8.7 months vs 23.1 months; p < 0.025) and PFS (2.5 vs 13.7 months; p < 0.018). The relative change in BFdecon (categorical) on day seven was a predictor of OS (HR 0.26, CI95: 0.06 to 0.93 p = 0.039) and PFS (HR 0.27, CI95: 0.09 to 0.85 p = 0.026). CONCLUSION: DCE-CT-identified parameters may serve as potential prognostic biomarkers at baseline and during early treatment in patients with NSCLC treated with immune checkpoint inhibitor therapy.

Quality of fluid balance charting and interventions to improve it: a systematic review.

INTRODUCTION: Fluid balance monitoring is pivotal to patients' health. Thus, fluid balance charting is an essential part of clinical nursing documentation. This systematic review aimed to investigate and describe the quality of fluid balance monitoring in medical, surgical and intensive care units, with an emphasis on the completeness of charting data, calculation errors and accuracy, and to evaluate methods used to improve fluid balance charting. MATERIALS AND METHODS: Quantitative studies involving adult patients and reporting data on fluid balance monitoring were included in the review. We searched MEDLINE, Embase, CINAHL and the Cochrane Library. The risk of bias in the included studies was assessed using tools developed by the Joanna Briggs Institute. RESULTS: We included a total of 23 studies, which involved 6649 participants. The studies were quasi-experimental, cohort or prevalence studies, and every third study was of low quality. Definitions of 'completeness' varied, as well as patient categories and time of evaluation. Eighteen studies reported the prevalence of patients with complete fluid balance charts; of those, 10 reported that not more than 50% of fluid balance charts were complete. Studies addressing calculation errors found them in 25%-35% of charts, including omissions of, for example, intravenous medications. The reported interventions consisted of various components such as policies, education, equipment, visual aids, surveillance and dissemination of results. Among studies evaluating interventions, only 38% (5 of 13) achieved compliance with at least 75% of complete fluid balance charts. Due to the heterogeneity of the studies, a meta-analysis was not possible. CONCLUSION: The quality of fluid balance charting is inadequate in most studies, and calculation errors influence quality. Interventions included several components, and the impact on the completion of fluid balance charts varied.

Safety, Feasibility, and Potential Clinical Efficacy of 40 Hz Invisible Spectral Flicker versus Placebo in Patients with Mild-to-Moderate Alzheimer's Disease: A Randomized, Placebo-Controlled, Double-Blinded, Pilot Study.

BACKGROUND: Recent studies suggested induction of 40 Hz neural activity as a potential treatment for Alzheimer's disease (AD). However, prolonged exposure to flickering light raises adherence and safety concerns, encouraging investigation of tolerable light stimulation protocols. OBJECTIVE: To investigate the safety, feasibility, and exploratory measures of efficacy. METHODS: This two-stage randomized placebo-controlled double-blinded clinical trial, recruited first cognitive healthy participants (n = 3/2 active/placebo), and subsequently patients with mild-to-moderate AD (n = 5/6, active/placebo). Participants were randomized 1:1 to receive either active intervention with 40 Hz Invisible Spectral Flicker (ISF) or placebo intervention with color and intensity matched non-flickering white light. RESULTS: Few and mild adverse events were observed. Adherence was above 86.1% of intended treatment days, with participants remaining in front of the device for >51.3 min (60 max) and directed gaze >34.9 min. Secondary outcomes of cognition indicate a tendency towards improvement in the active group compared to placebo (mean: -2.6/1.5, SD: 6.58/6.53, active/placebo) at week 6. Changes in hippocampal and ventricular volume also showed no tendency of improvement in the active group at week 6 compared to placebo. At week 12, a potential delayed effect of the intervention was seen on the volume of the hippocampus in the active group compared to placebo (mean: 0.34/-2.03, SD: 3.26/1.18, active/placebo), and the ventricular volume active group (mean: -0.36/2.50, SD: 1.89/2.05, active/placebo), compared to placebo. CONCLUSION: Treatment with 40 Hz ISF offers no significant safety or adherence concerns. Potential impact on secondary outcomes must be tested in larger scale clinical trials.

Novel Invisible Spectral Flicker Induces 40 Hz Neural Entrainment with Similar Spatial Distribution as 40 Hz Stroboscopic Light.

BACKGROUND: Exposure to 40 Hz stroboscopic light, for one hour a day, has previously been published as a potential treatment option for Alzheimer's disease in animal models. However, exposure for an hour a day to 40 Hz stroboscopic light can be strenuous and examining other types of 40 Hz inducing stimuli is paramount if chronic treatment is wanted. OBJECTIVE: A core assumption behind ensuring a therapeutic outcome is that the visual stimuli can induce 40 Hz gamma entrainment. Here, we examine whether a specific visual stimulus, 40 Hz invisible spectral flicker (ISF), can induce gamma entrainment and how it differs from both continuous light (CON) and 40 Hz stroboscopic light (STROBE). METHODS: The study included non-simultaneous EEG-fMRI neuroimaging of 13 young healthy volunteers during light exposure. Each light condition (i.e., CON, ISF, or STROBE) was active for 30 seconds followed immediately by the next. RESULTS: Entrainment of 40 Hz neural activity were significantly higher signal-to-noise ratio during exposure to ISF (mean: 3.03, 95% CI 2.07 to 3.99) and STROBE (mean: 12.04, 95% CI 10.18 to 13.87) compared to CON. Additionally STROBE had a higher entrainment than ISF (mean: 9.01, 95% CI 7.16 to 12.14). CONCLUSION: This study presents a novel method of 40 Hz entrainment using ISF. This enables the possibility of future randomized placebo-controlled clinical trials with acceptable double blinding due to the essentially imperceivable flicker, which is expected to substantially reduce discomfort compared to interventions with stroboscopic flicker.

An fMRI-compatible system for targeted electrical stimulation.

BACKGROUND: Neuromodulation is a rapidly expanding therapeutic option considered within neuropsychiatry, pain and rehabilitation therapy. Combining electrostimulation with feedback from fMRI can provide information about the mechanisms underlying the therapeutic effects, but so far, such studies have been hampered by the lack of technology to conduct safe and accurate experiments. Here we present a system for fMRI compatible electrical stimulation, and the first proof-of-concept neuroimaging data with deep brain stimulation (DBS) in pigs obtained with the device. NEW METHOD: The system consists of two modules, placed in the control and scanner room, connected by optical fiber. The system also connects to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) while we acquired BOLD responses in the STN and neocortex. RESULTS: We found that the system delivered robust electrical stimuli to the implanted electrode in sync with the preprogrammed fMRI sequence. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the STN. COMPARISONS WITH EXISTING METHOD: The system solves three major problems related to electric stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference with the MRI scanner. CONCLUSIONS: The fMRI compatible electrical stimulator circumvents previous problems related to electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters, and can be customized to electroceutical applications beyond DBS.