Karel Calero

Rubratoxin B elicits antioxidative and DNA repair responses in mouse brain

Rubratoxin B (RB) is a mycotoxin with potential neurotoxic effects that have not yet been characterized. Based on existing evidence that RB interferes with mitochondrial electron transport to produce oxidative stress in peripheral tissues, we hypothesized that RB would produce oxidative damage to macromolecules in specific brain regions. Parameters of oxidative DNA damage and repair, lipid peroxidation, and superoxide dismutase (SOD) activity were measured across six mouse brain regions 24 h after administration of a single dose of RB. Lipid peroxidation and oxidative DNA damage were either unchanged or decreased in all brain regions in RB-treated mice compared with vehicle-treated mice. Concomitant with these decreased indices of oxidative macromolecular damage, SOD activity was significantly increased in all brain regions. Oxyguanosine glycosylase activity (OGG1), a key enzyme in the repair of oxidized DNA, was significantly increased in three brain regions--cerebellum (CB), caudate/putamen (CP), and cortex (CX)--but not in the hippocampus (HP), midbrain (MB), and pons/medulla (PM). The RB-enhanced OGG1 catalytic activity in these brain regions was not due to increased OGG1 protein expression, but was a result of enhanced catalytic activity of the enzyme. In conclusion, specific brain regions responded to an acute dose of RB by significantly altering SOD and OGG1 activities to maintain the degree of oxidative DNA damage equal to, or less than, that of normal steady-state levels.

Delirium prevention in critically ill adults through an automated reorientation intervention – A pilot randomized controlled trial

Objectives Explore the effect of an automated reorientation intervention on ICU delirium in a prospective randomized controlled trial. Background Delirium is common in ICU patients, and negatively affects outcomes. Few prevention strategies have been tested. Methods Thirty ICU patients were randomized to 3 groups. Ten received hourly recorded messages in a family members voice during waking hours over 3 ICU days, 10 received the same messages in a non‐family voice, and 10 (control) did not receive any automated reorientation messages. The primary outcome was delirium free days during the intervention period (evaluated by CAM‐ICU). Groups were compared by Fishers Exact Test. Results The family voice group had more delirium free days than the non‐family voice group, and significantly more delirium free days (p = 0.0437) than the control group. Conclusions Reorientation through automated, scripted messages reduced incidence of delirium. Using identical scripted messages, family voice was more effective than non‐family voice.

Home Portable Sleep Testing Has Gone Global.

Journal of Clinical Sleep Medicine, Vol. 12, No. 1, 2016 In an effort to decrease wait times, decrease expense and expedite institution of therapy for obstructive sleep apnea (OSA), home sleep testing (HST) has become increasingly more popular since the 2007 AASM clinical guidelines on home portable monitoring.1 The term HST is not entirely accurate, as these devices do not measure sleep. They are respiratory monitors applied to the patient during the estimated sleep time. The term sleep apnea testing is preferred as this is geared towards establishing the diagnosis of OSA. Regardless, the HST is easy to perform and can be done in the comfort of the patient’s home environment. HST throughout the world has shown a good sensitivity and specificity for detecting OSA for patients with a high pretest probability.2 Scoring of these studies may be performed by computer only, computer assisted with manual oversight or by a trained specialist. Scoring criteria have been established by the AASM,3 but comparison of these criteria internationally has been limited. Magalang et al. examine the agreement between independent scorers in six countries using AASM scoring criteria from 2007.3–5 The initial studies were performed in a single center and then reviewed at different institutions. Apnea hypopnea index (AHI) had a strong correlation when scoring was performed from nasal pressure (NP) recordings. Hypopneas were more easily recognized from the transformed NP tracing, which has been previously demonstrated.6 NP and transformed NP tracings performed better than respiratory induction plethysmography (RIP) in the detection of apneas. The detection of central apneas had less sensitivity and specificity, however transformed NP waveform was superior to NP and RIP analysis for central apnea identification. Respiratory inductive plethysmography (RIP) waveform analysis was less effective for identification of apneas, probably because it is not calibrated in clinical practice. Even when calibrated, RIP may erroneously classify events as central since it does not detect respiratory effort in up to 9% of patients.7 Clinical interpretation of HST is at times troublesome because of recognition of sleep onset and offset as well as recognition of artifacts. Editing the data manually improves the accuracy of the study interpretation.8 These variables were appropriately excluded from this study since the aim was the analysis of the scored respiratory events. In practice, COMMENTARY

777: ACTIGRAPHY IN ASSESSMENT OF CIRCADIAN RHYTHM ALTERATIONS IN THE ICU.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) conducted February 2013 to January 2016. Adults ≥ 18 years with primary ICH that could have study drug administered within 24 hours of onset were included. Patients received an initial IV administration of 400mg MC followed by MC 400mg PO daily for 5 days. Serum was analyzed before and after the fifth PO dose, and at 1, 6, 12, 48, and 72 hours after the same dose in order to calculate an approximate Cpeak and t1/2 using targeted LC-MS/MS. This study was approved by the Augusta University Institutional Review Board. Results: A total of 16 consecutive eligible patients were enrolled, with 7 undergoing pharmacokinetic (PK) sampling. The study population had a mean age of 62 ± 12 years, (50% Caucasian, 50% African American, 35% male). MC was well tolerated. PK analysis revealed a t1/2 of 17.5 hours (SD±3.5). Average Cpeak one hour after the dose was 5.66 ± 2.54 mg/L. The time to Cpeak was estimated to be at least 6 hours. Concentrations remained >3 mcg/mL throughout the dosing interval in 5 patients, and 6 patients achieved this concentration at 1 hour. Conclusions: In ICH patients, PO MC absorption is delayed, leading to 1 hour concentrations much lower than expected (14.32 vs 5.66 mg/L). Critically ill ICH patients will likely need IV administration of large doses in order to ensure sufficient serum concentrations for neuroprotection.

Treating community-acquired pneumonia: To suppress or not to suppress? How much or what to suppress with? Those are the questions!

The article by Messika et al [1], in the Journal is very interesting and raises some important points and questions. They investigated whether acute exposure to nonsteroidal antiinflammatory drugs (NSAIDs) in the early stages of severe community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae would affect its presentation and outcome. They found that patients who took the NSAIDs were 20 years younger, had fewer comorbidities, and were more likely to be employed than those who did not receive them. Exposure to NSAIDs delayed intensive care unit (ICU) admission and antibiotic administration. Both groups had the same rates of respiratory failure and required the same ventilator support, although those who got NSAIDs had a lower pneumonia severity index, Simplified Acute Physiology Score II, and organ dysfunction and infection score. The confusion, (blood) urea, respiratory rate, blood pressure and aged 65 and the infective disease society of America ICU admission score was the same. They also found that pleural manifestations of S pneumoniae CAP were more frequent if NSAIDs were taken early in its course. In more than 80% of cases, health care workers provided the NSAIDs. Mortality at ICU discharge (P = .11) and mortality at hospital discharge (P = .11) were the same in both groups. The authors did not look at mortality at 1 or 5 years. The authors suggest that there are 2 reasons for their results. Firstly, the patients treated with NSAIDs usually did not receive antibiotics, until they reached the hospital. Secondly, NSAIDs may hamper the immune response, thus predisposing those who took them to a more severe pneumonia manifestation.