High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

Rethinking Remapping: Circuit Mechanisms of Recovery after Stroke.

Stroke is one of the most common causes of disability, and there are few treatments that can improve recovery after stroke. Therapeutic development has been hindered because of a lack of understanding of precisely how neural circuits are affected by stroke, and how these circuits change to mediate recovery. Indeed, some of the hypotheses for how the CNS changes to mediate recovery, including remapping, redundancy, and diaschisis, date to more than a century ago. Recent technological advances have enabled the interrogation of neural circuits with ever greater temporal and spatial resolution. These techniques are increasingly being applied across animal models of stroke and to human stroke survivors, and are shedding light on the molecular, structural, and functional changes that neural circuits undergo after stroke. Here we review these studies and highlight important mechanisms that underlie impairment and recovery after stroke. We begin by summarizing knowledge about changes in neural activity that occur in the peri-infarct cortex, specifically considering evidence for the functional remapping hypothesis of recovery. Next, we describe the importance of neural population dynamics, disruptions in these dynamics after stroke, and how allocation of neurons into spared circuits can restore functionality. On a more global scale, we then discuss how effects on long-range pathways, including interhemispheric interactions and corticospinal tract transmission, contribute to post-stroke impairments. Finally, we look forward and consider how a deeper understanding of neural circuit mechanisms of recovery may lead to novel treatments to reduce disability and improve recovery after stroke.

Voluntary Motor Command Release Coincides with Restricted Sensorimotor Beta Rhythm Phases.

Sensory perception and memory are enhanced during restricted phases of ongoing brain rhythms, but whether voluntary movement is constrained by brain rhythm phase is not known. Voluntary movement requires motor commands to be released from motor cortex (M1) and transmitted to spinal motoneurons and effector muscles. Here, we tested the hypothesis that motor commands are preferentially released from M1 during circumscribed phases of ongoing sensorimotor rhythms. Healthy humans of both sexes performed a self-paced finger movement task during electroencephalography (EEG) and electromyography (EMG) recordings. We first estimated the time of motor command release preceding each finger movement by subtracting individually measured corticomuscular transmission latencies from EMG-determined movement onset times. Then, we determined the phase of ipsilateral and contralateral sensorimotor mu (8-12 Hz) and beta (13-35 Hz) rhythms during release of each motor command. We report that motor commands were most often released between 120 and 140° along the contralateral beta cycle but were released uniformly along the contralateral mu cycle. Motor commands were also released uniformly along ipsilateral mu and beta cycles. Results demonstrate that motor command release coincides with restricted phases of the contralateral sensorimotor beta rhythm, suggesting that sensorimotor beta rhythm phase may sculpt the timing of voluntary human movement.SIGNIFICANCE STATEMENT Perceptual and cognitive function is optimal during specific brain rhythm phases. Although brain rhythm phase influences motor cortical neuronal activity and communication between the motor cortex and spinal cord, its role in voluntary movement is poorly understood. Here, we show that the motor commands needed to produce voluntary movements are preferentially released from the motor cortex during contralateral sensorimotor beta rhythm phases. Our findings are consistent with the notion that sensorimotor rhythm phase influences the timing of voluntary human movement.

Sensorimotor Oscillatory Phase-Power Interaction Gates Resting Human Corticospinal Output.

Oscillatory activity within sensorimotor networks is characterized by time-varying changes in phase and power. The influence of interactions between sensorimotor oscillatory phase and power on human motor function, like corticospinal output, is unknown. We addressed this gap in knowledge by delivering transcranial magnetic stimulation (TMS) to the human motor cortex during electroencephalography recordings in 20 healthy participants. Motor evoked potentials, a measure of corticospinal excitability, were categorized offline based on the mu (8-12 Hz) and beta (13-30 Hz) oscillatory phase and power at the time of TMS. Phase-dependency of corticospinal excitability was evaluated across a continuous range of power levels using trial-by-trial linear mixed-effects models. For mu, there was no effect of PHASE or POWER (P > 0.51), but a significant PHASE × POWER interaction (P = 0.002). The direction of phase-dependency reversed with changing mu power levels: corticospinal output was higher during mu troughs versus peaks when mu power was high while the opposite was true when mu power was low. A similar PHASE × POWER interaction was not present for beta oscillations (P > 0.11). We conclude that the interaction between sensorimotor oscillatory phase and power gates human corticospinal output to an extent unexplained by sensorimotor oscillatory phase or power alone.

Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study.

BACKGROUND: Cardiac surgery patients are at high risk for postoperative bleeding. Intravenous (IV) tranexamic acid (TxA) is a commonly used antifibrinolytic drug, but is associated with postoperative seizures. We conducted this pilot randomized controlled trial (RCT) to determine the feasibility of a larger trial that will be designed to investigate the impact of TxA administration route, intrapericardial (IP) vs IV, on postoperative bleeding and seizures. METHODS: In this single-center, double-blinded, pilot RCT we enrolled adult patients undergoing nonemergent on-pump cardiac operations through a median sternotomy. Participants were randomized to IP or IV TxA groups. The primary outcomes were cumulative chest tube drainage, transfusion requirements, and incidence of postoperative seizures. RESULTS: A total of 97 participants were randomized to the intervention and control groups. Baseline characteristics were similar in both groups. Most participants underwent a CABG and/or aortic valve replacement. There was no statistical difference. The IP TxA group was found to have a tendency for less chest tube drainage in comparison to the IV TxA group, 500.5 (370.0-700.0) and 540.0 (420.0-700.0) mL, respectively, which was not statistically significant (P = 0.2854). Fewer participants in the IP TxA group with cardiac tamponade and/or required a reoperation for bleeding and fewer packed red blood cell transfusions. None of the IP TxA group developed seizure vs one from the IV TxA group. CONCLUSION: This is the first known pilot RCT to investigate the role of TxA route of administration in open cardiac surgery. Intrapericardial TxA shows promising results with decreased bleeding, transfusion requirements, reoperations, and postoperative seizures. A larger RCT is needed to confirm these results and lead to a change in practice.

Survey of multinational surgical management practices in tetralogy of Fallot.

BACKGROUND: A wide variety of surgical strategies are used in tetralogy of Fallot repair. We sought to describe the international contemporary practice patterns for surgical management of tetralogy of Fallot. METHODS: Surgeons from 18 international paediatric cardiac surgery centres (representing over 1800 tetralogy of Fallot cases/year) completed a Research Electronic Data Capture-based survey. Participating countries include: China (4), India (2), Nepal (1), Korea (1), Indonesia (1), Saudi Arabia (3), Japan (1), Turkey (1), Australia (1), United States of America (2), and Canada (1). Summary measures were reported as means and counts (percentages). Responses were weighted based on case volume/centre. RESULTS: Primary repair is the prevalent strategy (83%) with variation in age at elective repair (range). Approximately 47% of sites use patient age as a factor in determining the strategy, with age 90% of all trans-annular repairs. CONCLUSIONS: In this cohort representing 11 countries, there is variation in tetralogy of Fallot surgical management with no consensus on standard of practice. A large international prospective cohort study would allow analysis of impact of underlying anatomy and repair strategy on early and late outcomes.

Probing phase- and frequency-dependent characteristics of cortical interneurons using combined transcranial alternating current stimulation and transcranial magnetic stimulation.

Paired-pulse transcranial magnetic stimulation (TMS) and peripheral stimulation combined with TMS can be used to study cortical interneuronal circuitry. By combining these procedures with concurrent transcranial alternating current stimulation (tACS), Guerra and colleagues recently showed that different cortical interneuronal populations are differentially modulated by the phase and frequency of tACS-imposed oscillations (Guerra A, Pogosyan A, Nowak M, Tan H, Ferreri F, Di Lazzaro V, Brown P. Cerebral Cortex 26: 3977-2990, 2016). This work suggests that different cortical interneuronal populations can be characterized by their phase and frequency dependency. Here we discuss how combining TMS and tACS can reveal the frequency at which cortical interneuronal populations oscillate, the neuronal origins of behaviorally relevant cortical oscillations, and how entraining cortical oscillations could potentially treat brain disorders.

Perturbation schedule does not alter retention of a locomotor adaptation across days.

Motor adaptation in response to gradual vs. abrupt perturbation schedules may involve different neural mechanisms, potentially leading to different levels of motor memory. However, no study has investigated whether perturbation schedules alter memory of a locomotor adaptation across days. We measured adaptation and retention (memory) of altered interlimb symmetry during walking in two groups of participants over 2 days. On day 1, participants adapted to either a single, large perturbation (abrupt schedule) or a series of small perturbations that increased in size over time (gradual schedule). Retention was examined on day 2. On day 1, initial swing time and foot placement symmetry error sizes differed between groups but overall adaptation magnitudes were similar. On day 2, participants in both groups showed similar retention, readaptation, and aftereffect sizes, although there were some trends for improved memory in the abrupt group. These results conflict with previous data but are consistent with newer studies reporting no behavioral differences following adaptation using abrupt vs. gradual schedules. Although memory levels were very similar between groups, we cannot rule out the possibility that the neural mechanisms underlying this memory storage differ. Overall, it appears that adaptation of locomotor patterns via abrupt and gradual perturbation schedules produces similar expression of locomotor memories across days.

Exploring barriers and enablers of antibiotic amnesty campaigns.

This editorial highlights the different barriers and enablers of antibiotic amnesty campaigns in community pharmacies. The main enablers of antibiotic amnesties included effective counselling and successful use of promotional resources, whilst the main barriers included lack of education in patients and staff. Enabling factors such as effective counselling and use of promotional resources should be continued with patients, whilst the main barriers can be tackled with provision of sufficient education, training, and knowledge for patients. Educating staff, by providing appropriate training to all staff members present in the pharmacy, can positively contribute to the success of antibiotic amnesty campaigns. The findings of this work can inform the development of interventions needed to improve antibiotic amnesties, resulting in more antibiotics being returned and contributing towards tackling the issue of antimicrobial resistance (AMR).

Acute pericarditis as the presenting symptom of a case of oesophageal carcinoma.

Oesophageal carcinoma is a globally prevalent form of cancer. Patients with advanced disease often experience progressive dysphagia and weight loss as initial symptoms, but pericarditis is an uncommon presentation. This study describes a young man who presented with pericarditis and was diagnosed with oesophageal squamous cell carcinoma. The patient's diagnosis came after presenting with intermittent chest pain. His diagnostic tests included an ECG showing ST elevation, echocardiography showing pericardial effusion and elevated inflammatory markers. His imaging tests revealed a neoplastic lesion in the lower oesophagus with metastases. He was initially treated as a case of pericarditis, followed by palliative chemotherapy for his cancer. Pericarditis, as the initial presentation of oesophageal carcinoma, is rare. There have only been 19 cases reported and published in the literature. Treatment depends on the stage of the disease. This case emphasises the importance of considering malignancy in unusual presentations of pericarditis, especially in young patients.

Personalized whole-brain activity patterns predict human corticospinal tract activation in real-time.

BACKGROUND: Transcranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are therefore needed. METHODS: As a first step towards this goal, we tested a novel machine learning-based EEG-TMS system that identifies personalized brain activity patterns reflecting strong and weak corticospinal tract (CST) output (strong and weak CST states) in healthy adults in real-time. Participants completed a single-session study that included the acquisition of a TMS-EEG-EMG training dataset, personalized classifier training, and real-time EEG-informed single pulse TMS during classifier-predicted personalized CST states. RESULTS: MEP amplitudes elicited in real-time during personalized strong CST states were significantly larger than those elicited during personalized weak and random CST states. MEP amplitudes elicited in real-time during personalized strong CST states were also significantly less variable than those elicited during personalized weak CST states. Personalized CST states lasted for ~1-2 seconds at a time and ~1 second elapsed between consecutive similar states. Individual participants exhibited unique differences in spectro-spatial EEG patterns between personalized strong and weak CST states. CONCLUSION: Our results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans. These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function.

Motor sequence learning-induced corticospinal plasticity is biased towards sensorimotor mu rhythm peak phases.

Motor cortical (M1) transcranial magnetic stimulation (TMS) increases corticospinal output and improves motor learning when delivered during sensorimotor mu rhythm trough but not peak phases, suggesting that mechanisms supporting motor learning may be most active during mu trough phases. If so, learning-related corticospinal plasticity should be most evident during mu trough phases. Healthy adults were assigned to either a sequence or control group. Participants in the sequence group practiced the implicit serial reaction time task (SRTT), which contained an embedded, repeating 12-item sequence. Participants in the control group practiced a version of the SRTT that contained no sequence. We measured mu phase-independent and phase-dependent MEP amplitudes using EEG-informed single-pulse TMS before, immediately, and 30 minutes after the SRTT in both groups. All participants performed a retention test one hour after SRTT acquisition. In both groups, mu phase-independent MEP amplitudes increased following SRTT acquisition, but the pattern of mu phase-dependent MEP amplitude increases after SRTT acquisition differed between groups. MEP amplitude changes from baseline to 30 minutes after SRTT acquisition more strongly differed across phases in the control relative to the sequence group, with the control group showing smaller increases in peak- than trough-specific MEPs. Contrary to our original hypothesis, results revealed that sequence learning recruits peak- rather than trough-specific neurophysiological mechanisms. Overall, these findings suggest that mu peak phases may provide protected time windows for motor memory consolidation and demonstrate the presence of a mu phase-dependent motor learning mechanism in the human brain. Significance statement: Recent work suggests that the neurophysiological mechanisms supporting motor learning may be most active during sensorimotor mu rhythm trough phases. Here, we evaluated this possibility by measuring mu phase-dependent corticospinal plasticity induced by motor sequence learning. Results provide first evidence that motor sequence learning produced corticospinal plasticity that was more pronounced during mu peak than trough phases, demonstrating the presence of a phase-dependent learning mechanism within the human motor system.

A locomotor adaptation including explicit knowledge and removal of postadaptation errors induces complete 24-hour retention.

Locomotor patterns are generally very consistent but also contain a high degree of adaptability. Motor adaptation is a short-term type of learning that utilizes this plasticity to alter locomotor behaviors quickly and transiently. In this study, we used a variation of an adaptation paradigm in order to test whether explicit information as well as the removal of the visual error signal after adaptation could improve retention of a newly learned walking pattern 24 h later. On two consecutive days of testing, participants walked on a treadmill while viewing a visual display that showed erroneous feedback of swing times for each leg. Participants were instructed to use this feedback to monitor and adjust swing times so they appeared symmetric within the display. This was achieved by producing a novel interlimb asymmetry between legs. For both legs, we measured adaptation magnitudes and rates and immediate and 24-h retention magnitudes. Participants showed similar adaptation on both days but a faster rate of readaptation on day 2. There was complete retention of adapted swing times on the increasing leg (i.e., no evidence of performance decay over 24 h). Overall, these findings suggest that the inclusion of explicit information and the removal of the visual error signal are effective in inducing full retention of adapted increases in swing time over a moderate (24 h) interval of time.

Decoding personalized motor cortical excitability states from human electroencephalography.

Brain state-dependent transcranial magnetic stimulation (TMS) requires real-time identification of cortical excitability states. Current approaches deliver TMS during brain states that correlate with motor cortex (M1) excitability at the group level. Here, we hypothesized that machine learning classifiers could successfully discriminate between high and low M1 excitability states in individual participants using information obtained from low-density electroencephalography (EEG) signals. To test this, we analyzed a publicly available dataset that delivered 600 single TMS pulses to the right M1 during EEG and electromyography (EMG) recordings in 20 healthy adults. Multivariate pattern classification was used to discriminate between brain states during which TMS evoked small and large motor-evoked potentials (MEPs). Results show that personalized classifiers successfully discriminated between low and high M1 excitability states in 80% of tested participants. MEPs elicited during classifier-predicted high excitability states were significantly larger than those elicited during classifier-predicted low excitability states in 90% of tested participants. Personalized classifiers did not generalize across participants. Overall, results show that individual participants exhibit unique brain activity patterns which predict low and high M1 excitability states and that these patterns can be efficiently captured using low-density EEG signals. Our findings suggest that deploying individualized classifiers during brain state-dependent TMS may enable fully personalized neuromodulation in the future.

Pharmacy and medical students' attitudes and perspectives on social media usage and e-professionalism in United Arab Emirates.

BACKGROUND: It is imperative to establish how students view and present themselves on social media and to assess level of awareness regarding the implications of their social media presence, e-professionalism, and accountability. The study objectives were to: 1) Determine the social media usage levels among medical and pharmacy students in the United Arab Emirates (UAE); 2) Characterize the students' views and perceptions, including their awareness of e-professionalism; and 3) Compare the responses in behavior between the two groups. METHODOLOGY: A cross-sectional study was performed on 575 undergraduate students from two study disciplines, pharmacy (n = 325) and medicine (n = 250). Minor revisions were made to previously validated assessment tools and pilot tested. The study sample included students from five different universities across the country. RESULTS: In comparison to medical students, pharmacy students were observed to use social media more for learning purposes (χ2 = 6.8, P < .05). However, medical students' opinions reflected more strongly on the context of accountability and e-professionalism (χ2 = 15.8, P < .05). A considerable proportion (89%) of students felt it was discriminatory for prospective employers to use their social media profile information for investigative purposes while hiring. One-third of respondents reported sharing information that they would not want their employers to view, and 67.1% reported the same for information relevant to patients. CONCLUSION: The research findings converge to address the need for educators and administrators in the UAE to develop guidelines concerning its safe use and proactively integrate e-professionalism into their respective curriculum.

Phase-dependent offline enhancement of human motor memory.

BACKGROUND: Skill learning engages offline activity in the primary motor cortex (M1). Sensorimotor cortical activity oscillates between excitatory trough and inhibitory peak phases of the mu (8-12 Hz) rhythm. We recently showed that these mu phases influence the magnitude and direction of neuroplasticity induction within M1. However, the contribution of M1 activity during mu peak and trough phases to human skill learning has not been investigated. OBJECTIVE: To evaluate the effects of phase-dependent TMS during mu peak and trough phases on offline learning of a newly-acquired motor skill. METHODS: On Day 1, three groups of healthy adults practiced an explicit motor sequence learning task with their non-dominant left hand. After practice, phase-dependent TMS was applied to the right M1 during either mu peak or mu trough phases. The third group received sham TMS during random mu phases. On Day 2, all subjects were re-tested on the same task to evaluate offline learning. RESULTS: Subjects who received phase-dependent TMS during mu trough phases showed increased offline skill learning compared to those who received phase-dependent TMS during mu peak phases or sham TMS during random mu phases. Additionally, phase-dependent TMS during mu trough phases elicited stronger whole-brain broadband oscillatory power responses than phase-dependent TMS during mu peak phases. CONCLUSIONS: We conclude that sensorimotor mu trough phases reflect brief windows of opportunity during which TMS can strengthen newly-acquired skill memories.

Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor µ-rhythm.

BACKGROUND: Neural oscillations reflect rapidly changing brain excitability states. We have demonstrated previously with EEG-triggered transcranial magnetic stimulation (TMS) of human motor cortex that the positive vs. negative peak of the sensorimotor µ-oscillation reflect corticospinal low-vs. high-excitability states. In vitro experiments showed that induction of long-term depression (LTD) by low-frequency stimulation depends on the postsynaptic excitability state. OBJECTIVE/HYPOTHESIS: We tested the hypothesis that induction of LTD-like corticospinal plasticity in humans by 1 Hz repetitive TMS (rTMS) is enhanced when rTMS is synchronized with the low-excitability state, but decreased or even shifted towards long-term (LTP)-like plasticity when synchronized with the high-excitability state. METHODS: We applied real-time EEG-triggered 1-Hz-rTMS (900 pulses) to the hand area of motor cortex in healthy subjects. In a randomized double-blind three-condition crossover design, pulses were synchronized to either the positive or negative peak of the sensorimotor µ-oscillation, or were applied at random phase (control). The amplitude of motor evoked potentials was recorded as an index of corticospinal excitability before and after 1-Hz-rTMS. RESULTS: 1-Hz-rTMS at random phase resulted in a trend towards LTD-like corticospinal plasticity. RTMS in the positive peak condition (i.e., the low-excitability state) induced significant LTD-like plasticity. RTMS in the negative peak condition (i.e., the high-excitability state) showed a trend towards LTP-like plasticity, which was significantly different from the other two conditions. CONCLUSION: The level of corticospinal depolarization reflected by phase of the µ-oscillation determines the degree of corticospinal plasticity induced by low-frequency rTMS, a finding that may guide future personalized therapeutic stimulation.