Time since liver transplant and immunosuppression withdrawal outcomes: Systematic review and individual patient data meta-analysis.

BACKGROUND & AIMS: Successful immunosuppression withdrawal (ISW) is possible for a subfraction of liver transplant (LT) recipients but the factors that define the risk of ISW failure are largely unknown. One candidate prognostic factor for ISW success or operational tolerance (OT) is longer time between LT and ISW which we term "pre-withdrawal time". To clarify the impact of pre-withdrawal time span on subsequent ISW success or failure, we conducted a systematic review with meta-analysis. METHODS: We systematically interrogated the literature for LT recipient ISW studies reporting pre-withdrawal time. Eligible articles from Embase, Medline, and the Cochrane Central Register of Controlled Trials were used for backward and forward citation searching. Pre-withdrawal time individual patient data (IPD) was requested from authors. Pooled mean differences and time-response curves were calculated using random-effects meta-analyses. RESULTS: We included 17 studies with 691 patients, 15 of which (620 patients) with IPD. Study-level risk of bias was heterogeneous. Mean pre-withdrawal time was greater by 427 days [95% confidence interval (CI) 67-788] in OT compared to non-OT patients. This increase was potentiated to 799 days (95% CI 369-1229) or 1074 days (95% CI 685-1463) when restricting analysis to adult or European study participants. In time-response meta-analysis for adult or European ISW candidates, likelihood of OT increased by 7% (95% CI 4-10%) per year after LT (GRADE low- and moderate-certainty of evidence, respectively). CONCLUSIONS: Our data support the impact of pre-withdrawal time in ISW decision-making for adult and European LT recipients. PROSPERO REGISTRATION: CRD42021272995.

Two motor neuron synergies, invariant across ankle joint angles, activate the triceps surae during plantarflexion.

Recent studies have suggested that the nervous system generates movements by controlling groups of motor neurons (synergies) that do not always align with muscle anatomy. In this study, we determined whether these synergies are robust across tasks with different mechanical constraints. We identified motor neuron synergies using principal component analysis (PCA) and cross-correlations between smoothed discharge rates of motor neurons. In part 1, we used simulations to validate these methods. The results suggested that PCA can accurately identify the number of common inputs and their distribution across active motor neurons. Moreover, the results confirmed that cross-correlation can separate pairs of motor neurons that receive common inputs from those that do not receive common inputs. In part 2, 16 individuals performed plantarflexion at three ankle angles while we recorded EMG signals from the gastrocnemius lateralis (GL) and medialis (GM) and the soleus (SOL) with grids of surface electrodes. The PCA revealed two motor neuron synergies. These motor neuron synergies were relatively stable, with no significant differences in the distribution of motor neuron weights across ankle angles (P = 0.62). When the cross-correlation was calculated for pairs of motor units tracked across ankle angles, we observed that only 13.0% of pairs of motor units from GL and GM exhibited significant correlations of their smoothed discharge rates across angles, confirming the low level of common inputs between these muscles. Overall, these results highlight the modularity of movement control at the motor neuron level, suggesting a sensible reduction of computational resources for movement control. KEY POINTS: The CNS might generate movements by activating groups of motor neurons (synergies) with common inputs. We show here that two main sources of common inputs drive the motor neurons innervating the triceps surae muscles during isometric ankle plantarflexions. We report that the distribution of these common inputs is globally invariant despite changing the mechanical constraints of the tasks, i.e. the ankle angle. These results suggest the functional relevance of the modular organization of the CNS to control movements.

Magnetic Dynamo Caused by Axions in Neutron Stars.

The coupling between axions and photons modifies Maxwell's equations, introducing a dynamo term in the magnetic induction equation. In neutron stars, for critical values of the axion decay constant and axion mass, the magnetic dynamo mechanism increases the total magnetic energy of the star. We show that this generates substantial internal heating due to enhanced dissipation of crustal electric currents. These mechanisms would lead magnetized neutron stars to increase their magnetic energy and thermal luminosity by several orders of magnitude, in contrast to observations of thermally emitting neutron stars. To prevent the activation of the dynamo, bounds on the allowed axion parameter space can be derived.

Exoskeleton-based training improves walking independence in incomplete spinal cord injury patients: results from a randomized controlled trial.

BACKGROUND: In recent years, ambulatory lower limb exoskeletons are being gradually introduced into the clinical practice to complement walking rehabilitation programs. However, the clinical evidence of the outcomes attained with these devices is still limited and nonconclusive. Furthermore, the user-to-robot adaptation mechanisms responsible for functional improvement are still not adequately unveiled. This study aimed to (1) assess the safety and feasibility of using the HANK exoskeleton for walking rehabilitation, and (2) investigate the effects on walking function after a training program with it. METHODS: A randomized controlled trial was conducted including a cohort of 23 patients with less than 1 year since injury, neurological level of injury (C2-L4) and severity (American Spinal Cord Injury Association Impairment Scale [AIS] C or D). The intervention was comprised of 15 one-hour gait training sessions with lower limb exoskeleton HANK. Safety was assessed through monitoring of adverse events, and pain and fatigue through a Visual Analogue Scale. LEMS, WISCI-II, and SCIM-III scales were assessed, along with the 10MWT, 6MWT, and the TUG walking tests (see text for acronyms). RESULTS: No major adverse events were reported. Participants in the intervention group (IG) reported 1.8 cm (SD 1.0) for pain and 3.8 (SD 1.7) for fatigue using the VAS. Statistically significant differences were observed for the WISCI-II for both the "group" factor (F = 16.75, p < 0.001) and "group-time" interactions (F = 8.87; p < 0.01). A post-hoc analysis revealed a statistically significant increase of 3.54 points (SD 2.65, p < 0.0001) after intervention for the IG but not in the CG (0.7 points, SD 1.49, p = 0.285). No statistical differences were observed between groups for the remaining variables. CONCLUSIONS: The use of HANK exoskeleton in clinical settings is safe and well-tolerated by the patients. Patients receiving treatment with the exoskeleton improved their walking independence as measured by the WISCI-II after the treatment.

Automatic Detection of Magnetic Disturbances in Magnetic Inertial Measurement Unit Sensors Based on Recurrent Neural Networks.

This paper proposes a new methodology for the automatic detection of magnetic disturbances from magnetic inertial measurement unit (MIMU) sensors based on deep learning. The proposed approach considers magnetometer data as input to a long short-term memory (LSTM) neural network and obtains a labeled time series output with the posterior probabilities of magnetic disturbance. We trained our algorithm on a data set that reproduces a wide range of magnetic perturbations and MIMU motions in a repeatable and reproducible way. The model was trained and tested using 15 folds, which considered independence in sensor, disturbance direction, and signal type. On average, the network can adequately detect the disturbances in 98% of the cases, which represents a significant improvement over current threshold-based detection algorithms.

Classification of Kinematic and Electromyographic Signals Associated with Pathological Tremor Using Machine and Deep Learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Decreased Long-Term Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Immunity in Liver Transplantation Recipients 12 Months After Coronavirus Disease 2019.

Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients.

A unified scheme for the benchmarking of upper limb functions in neurological disorders.

BACKGROUND: In neurorehabilitation, we are witnessing a growing awareness of the importance of standardized quantitative assessment of limb functions. Detailed assessments of the sensorimotor deficits following neurological disorders are crucial. So far, this assessment has relied mainly on clinical scales, which showed several drawbacks. Different technologies could provide more objective and repeatable measurements. However, the current literature lacks practical guidelines for this purpose. Nowadays, the integration of available metrics, protocols, and algorithms into one harmonized benchmarking ecosystem for clinical and research practice is necessary. METHODS: This work presents a benchmarking framework for upper limb capacity. The scheme resulted from a multidisciplinary and iterative discussion among several partners with previous experience in benchmarking methodology, robotics, and clinical neurorehabilitation. We merged previous knowledge in benchmarking methodologies for human locomotion and direct clinical and engineering experience in upper limb rehabilitation. The scheme was designed to enable an instrumented evaluation of arm capacity and to assess the effectiveness of rehabilitative interventions with high reproducibility and resolution. It includes four elements: (1) a taxonomy for motor skills and abilities, (2) a list of performance indicators, (3) a list of required sensor modalities, and (4) a set of reproducible experimental protocols. RESULTS: We proposed six motor primitives as building blocks of most upper-limb daily-life activities and combined them into a set of functional motor skills. We identified the main aspects to be considered during clinical evaluation, and grouped them into ten motor abilities categories. For each ability, we proposed a set of performance indicators to quantify the proposed ability on a quantitative and high-resolution scale. Finally, we defined the procedures to be followed to perform the benchmarking assessment in a reproducible and reliable way, including the definition of the kinematic models and the target muscles. CONCLUSIONS: This work represents the first unified scheme for the benchmarking of upper limb capacity. To reach a consensus, this scheme should be validated with real experiments across clinical conditions and motor skills. This validation phase is expected to create a shared database of human performance, necessary to have realistic comparisons of treatments and drive the development of new personalized technologies.

Emerging Role of NLRP3 Inflammasome and Pyroptosis in Liver Transplantation.

The nucleotide-binding domain leucine-rich repeat-receptor, pyrin domain-containing-3 (NLRP3) inflammasome contributes to the inflammatory response by activating caspase-1, which in turn participates in the maturation of interleukin (IL)-1ß and IL-18, which are mainly secreted via pyroptosis. Pyroptosis is a lytic type of cell death that is controlled by caspase-1 processing gasdermin D. The amino-terminal fragment of gasdermin D inserts into the plasma membrane, creating stable pores and enabling the release of several proinflammatory factors. The activation of NLRP3 inflammasome and pyroptosis has been involved in the progression of liver fibrosis and its end-stage cirrhosis, which is among the main etiologies for liver transplantation (LT). Moreover, the NLRP3 inflammasome is involved in ischemia-reperfusion injury and early inflammation and rejection after LT. In this review, we summarize the recent literature addressing the role of the NLRP3 inflammasome and pyroptosis in all stages involved in LT and argue the potential targeting of this pathway as a future therapeutic strategy to improve LT outcomes. Likewise, we also discuss the impact of graft quality influenced by donation after circulatory death and the expected role of machine perfusion technology to modify the injury response related to inflammasome activation.

Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

Effects of gravity and kinematic constraints on muscle synergies in arm cycling.

Arm cycling is a bimanual motor task used in medical rehabilitation and in sports training. Understanding how muscle coordination changes across different biomechanical constraints in arm cycling is a step toward improved rehabilitation approaches. This exploratory study aims to get new insights on motor control during arm cycling. To achieve our main goal, we used the muscle synergies analysis to test three hypotheses: 1) body position with respect to gravity (sitting and supine) has an effect on muscle synergies; 2) the movement size (crank length) has an effect on the synergistic behavior; 3) the bimanual cranking mode (asynchronous and synchronous) requires different synergistic control. Thirteen able-bodied volunteers performed arm cranking on a custom-made device with unconnected cranks, which allowed testing three different conditions: body position (sitting vs. supine), crank length (10 cm vs. 15 cm), and cranking mode (synchronous vs. asynchronous). For each of the eight possible combinations, subjects cycled for 30 s while electromyography of eight muscles (four from each arm) were recorded: biceps brachii, triceps brachii, anterior deltoid, and posterior deltoid. Muscle synergies in this eight-dimensional muscle space were extracted by nonnegative matrix factorization. Four synergies accounted for over 90% of muscle activation variances in all conditions. Results showed that synergies were affected by body position and cranking mode but practically unaffected by movement size. These results suggest that the central nervous system may employ different motor control strategies in response to external constraints such as cranking mode and body position during arm cycling.NEW & NOTEWORTHY Recent studies analyzed muscle synergies in lower limb cycling. Here, we examine upper limb cycling and specifically the effect of body position with respect to gravity, movement size, and cranking mode on muscle coordination during arm cranking tasks. We show that altered body position and cranking mode affects modular organization of muscle activities. To our knowledge, this is the first study assessing motor control through muscle synergies framework during upper limb cycling with different constraints.

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients.

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.

Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.

BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.

EEG hyperscanning in motor rehabilitation: a position paper.

Studying the human brain during interpersonal interaction allows us to answer many questions related to motor control and cognition. For instance, what happens in the brain when two people walking side by side begin to change their gait and match cadences? Adapted from the neuroimaging techniques used in single-brain measurements, hyperscanning (HS) is a technique used to measure brain activity from two or more individuals simultaneously. Thus far, HS has primarily focused on healthy participants during social interactions in order to characterize inter-brain dynamics. Here, we advocate for expanding the use of this electroencephalography hyperscanning (EEG-HS) technique to rehabilitation paradigms in individuals with neurological diagnoses, namely stroke, spinal cord injury (SCI), Parkinson's disease (PD), and traumatic brain injury (TBI). We claim that EEG-HS in patient populations with impaired motor function is particularly relevant and could provide additional insight on neural dynamics, optimizing rehabilitation strategies for each individual patient. In addition, we discuss future technologies related to EEG-HS that could be developed for use in the clinic as well as technical limitations to be considered in these proposed settings.

Human-machine-human interaction in motor control and rehabilitation: a review.

BACKGROUND: Human-human (HH) interaction mediated by machines (e.g., robots or passive sensorized devices), which we call human-machine-human (HMH) interaction, has been studied with increasing interest in the last decade. The use of machines allows the implementation of different forms of audiovisual and/or physical interaction in dyadic tasks. HMH interaction between two partners can improve the dyad's ability to accomplish a joint motor task (task performance) beyond either partner's ability to perform the task solo. It can also be used to more efficiently train an individual to improve their solo task performance (individual motor learning). We review recent research on the impact of HMH interaction on task performance and individual motor learning in the context of motor control and rehabilitation, and we propose future research directions in this area. METHODS: A systematic search was performed on the Scopus, IEEE Xplore, and PubMed databases. The search query was designed to find studies that involve HMH interaction in motor control and rehabilitation settings. Studies that do not investigate the effect of changing the interaction conditions were filtered out. Thirty-one studies met our inclusion criteria and were used in the qualitative synthesis. RESULTS: Studies are analyzed based on their results related to the effects of interaction type (e.g., audiovisual communication and/or physical interaction), interaction mode (collaborative, cooperative, co-active, and competitive), and partner characteristics. Visuo-physical interaction generally results in better dyadic task performance than visual interaction alone. In cases where the physical interaction between humans is described by a spring, there are conflicting results as to the effect of the stiffness of the spring. In terms of partner characteristics, having a more skilled partner improves dyadic task performance more than having a less skilled partner. However, conflicting results were observed in terms of individual motor learning. CONCLUSIONS: Although it is difficult to draw clear conclusions as to which interaction type, mode, or partner characteristic may lead to optimal task performance or individual motor learning, these results show the possibility for improved outcomes through HMH interaction. Future work that focuses on selecting the optimal personalized interaction conditions and exploring their impact on rehabilitation settings may facilitate the transition of HMH training protocols to clinical implementations.

Peripheral electrical stimulation to reduce pathological tremor: a review.

Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.

Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again.

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD-LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD-LT immediately after each DCD-LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut-off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).