Continuously increased generation of ROS in human plasma after cardiac arrest as determined by Amplex Red oxidation.

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders. We found significantly increased AR oxidation rates lasting for 4 h in post-CA rat plasma compared to baseline. AR oxidation was unchanged with removal of horseradish peroxidase or addition of catalase. However, adding carboxylesterase inhibitors significantly decreased AR oxidation in rat plasma, which implicated increased carboxylesterase activity, not ROS leading to increased AR oxidation. AR oxidation rates were also significantly increased in human CA patient plasma compared to control and this increase persisted even with carboxylesterase inhibition, suggesting continuously increased ROS-generation within plasma post-CA in humans. The increased ROS generation may be one major source of injury post-CA that may be mitigated with antioxidative therapeutic strategies that can manage the ROS systemically generated in plasma over time.KEY POLICY HIGHLIGHTSWe examined the potential of plasma as a source of ROS generation post-cardiac arrestRat cardiac arrest was used to guide the application of Amplex Red in human plasmaROS generation in plasma is significantly increased after cardiac arrest in humansScavenging excessive ROS in post-resuscitation plasma may improve outcomes of patients.

Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect.

Median Nerve Stimulation for Treatment of Tics: A 4-Week Open Trial with Ecological Momentary Assessment.

Median nerve stimulation (MNS) at 10-12 Hz was recently proposed as a treatment for Tourette syndrome and other chronic tic disorders (TS/CTD). We report on 31 participants ages 15-64 with TS/CTD in an open-label, comparative (within-group, several time points) study of MNS (ClinicalTrials.gov registration number NCT05016765). Participants were recruited from completers of a randomized controlled trial (RCT) of MNS and were given a transcutaneous electrical nerve stimulation (TENS) unit to use as desired for 12 Hz MNS for 4 weeks. Participants were instructed to complete surveys regarding tic symptoms and stimulation discomfort before and after stimulation, as well as twice daily when randomly prompted by text message. Participants also completed an extensive final survey. Twenty-seven participants completed the study. Median device use was 1.5 days per week and 50 min per day used. Tic frequency improved during MNS (mean improvement: 1.0 on a 0-5 scale, p < 0.001), as did tic intensity (mean improvement: 0.9, p < 0.001). Mean discomfort was mild (1.2 on a 3-point scale). In total, 21 participants (78%) planned to continue using the device. Participants' results in this study did not correlate significantly with their results in the blinded RCT. We found MNS to improve tic frequency and intensity with minimal side effects.

Peripheral nerve induction of inhibitory brain circuits to treat Tourette syndrome: A randomized crossover trial.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained sensorimotor cortex EEG signal, and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested and stimulation blocks lasted only 1 minute. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity and urges without significant difference. Participant masking was effective and there was no carryover effect. Several participants described dramatic benefit. Discomfort was minimal. MNS benefit did not persist after the end of stimulation. These results replicate the tic benefit from MNS, but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain benefit; alternatively, these data do not exclude a placebo effect. Registration: ClinicalTrials.gov , NCT04731714 .

Why Tic Severity Changes from Then to Now and from Here to There.

Much of the research regarding Tourette's syndrome (TS) has focused on why certain individuals develop tics while others do not. However, a separate line of research focuses on the momentary influences that cause tics to increase or decrease in patients who are already known to have TS or another chronic tic disorder (CTD). Environmental and internal variables such as fatigue, anxiety, and certain types of thoughts all have been shown to worsen tic severity and may even overcome the positive effects of treatment. Other influences such as stress, distraction, and being observed have had mixed effects in the various studies that have examined them. Still, other variables such as social media exposure and dietary habits have received only minimal research attention and would benefit from additional study. Understanding the impact of these environmental and internal influences provides an opportunity to improve behavioral treatments for TS/CTD and to improve the lives of those living with these conditions. This review will examine the current literature on how these moment-to-moment influences impact tic expression in those with TS/CTD.

Prevalence, Trends, and Outcomes of Higher-Risk Percutaneous Coronary Interventions Among Patients Without Acute Coronary Syndromes.

BACKGROUND/PURPOSE: Patients and lesions at a higher procedural risk for percutaneous coronary intervention (PCI) are an understudied population. We examined the frequency, clinical characteristics, and outcomes of higher risk and non-higher risk PCIs at a large tertiary center. METHODS/MATERIALS: The following procedures were considered higher risk: unprotected left main PCI, chronic total occlusion PCI, PCI requiring atherectomy, multivessel PCI, bifurcation PCI, PCI in prior coronary artery bypass graft surgery (CABG) patients, pre-PCI left ventricular ejection fraction ≤30%, or use of hemodynamic support. RESULTS: Of the 1975 PCIs performed from 6/29/09 to 12/30/2016 in patients without acute coronary syndromes, 1230 (62%) were higher risk. Patients undergoing higher risk PCI were more likely to have a history of CABG, myocardial infarction, PCI, cerebrovascular disease, peripheral arterial disease, or congestive heart failure. Higher risk PCIs required more stents (2.0 vs. 1.0, p < 0.001), and had longer median fluoroscopy times (17.3 vs. 8.5 min, p < 0.001) and higher median contrast doses (160 vs. 120 mL, p < 0.001). In higher risk PCIs, the risks for technical failure and periprocedural complications were 2.9 (95% CI 1.2-7.4) times and 2.2 (95% CI 0.9-5.4) times higher as compared with non-higher risk PCI procedures. CONCLUSIONS: In summary, over half of the PCIs performed in non-acute coronary syndrome patients were higher risk and were associated with lower odds of technical success and higher periprocedural complication rates as compared with non-higher risk PCIs. SUMMARY: We examined the frequency, clinical characteristics, and outcomes of higher risk and non-higher risk PCIs at a large tertiary center. Higher risk PCI was associated with lower odds of technical and procedural success and higher odds of procedural complications as compared with non-higher risk PCI. However, the risk/benefit ratio may still be favorable for many of these higher-risk patients and should be estimated on a case by case basis.

Impact of sleep deprivation on the outcomes of percutaneous coronary intervention.

OBJECTIVES: This study sought to compare the clinical outcomes of percutaneous coronary interventions (PCIs) performed by sleep deprived and non-sleep deprived operators. BACKGROUND: Interventional cardiologists are at risk for sleep deprivation as they often have to perform emergent procedures at night, but the effects of sleep deprivation on clinical outcomes have received limited study. METHODS: We examined the frequency, clinical characteristics, and outcomes of daytime PCIs performed by sleep deprived and non-sleep deprived operators at a tertiary medical center. Operators were considered sleep deprived when performing a daytime (7 am-11:59 pm) procedure preceded by a nighttime (12 am-6:59 am) procedure on the same date. RESULTS: Of the 12,680 daytime PCIs performed from 6/29/09 to 12/30/2016, 367 (2.9%) were performed by sleep deprived operators. Patients undergoing PCI performed by a sleep deprived operator were more likely to be younger, white, and to present with ST-elevation acute myocardial infarction (STEMI). The incidence of in-hospital death (1.1% vs. 1.3%, P = 1.0) and bleeding within 72 hr (3.9% vs. 2.9%, P = 0.29) were similar for procedures performed by sleep-deprived and non-sleep deprived operators. When the sleep deprived group was further stratified based on degree of sleep deprivation or length of sleep interruption, differences in mortality and total bleeding remained non-significant. CONCLUSIONS: In this large single center study, operator sleep deprivation did not appear to adversely impact PCI outcomes.