Bioelectronic medicine最新文献

Background: Integrating advanced machine-learning (ML) algorithms into clinical practice is challenging and requires interdisciplinary collaboration to develop transparent, interpretable, and ethically sound clinical decision support (CDS) tools. We aimed to design a ML-driven CDS tool to predict opioid overdose risk and gather feedback for its integration into the University of Florida Health (UFHealth) electronic health record (EHR) system.

Methods: We used user-centered design methods to integrate the ML algorithm into the EHR system. The backend and UI design sub-teams collaborated closely, both informed by user feedback sessions. We conducted seven user feedback sessions with five UF Health primary care physicians (PCPs) to explore aspects of CDS tools, including workflow, risk display, and risk mitigation strategies. After customizing the tool based on PCPs' feedback, we held two rounds of one-on-one usability testing sessions with 8 additional PCPs to gather feedback on prototype alerts. These sessions informed iterative UI design and backend processes, including alert frequency and reappearance circumstances.

Results: The backend process development identified needs and requirements from our team, information technology, UFHealth, and PCPs. Thirteen PCPs (male = 62%, White = 85%) participated across 7 user feedback sessions and 8 usability testing sessions. During the user feedback sessions, PCPs (n = 5) identified flaws such as the term "high risk" of overdose potentially leading to unintended consequences (e.g., immediate addiction services referrals), offered suggestions, and expressed trust in the tool. In the first usability testing session, PCPs (n = 4) emphasized the need for natural risk presentation (e.g., 1 in 200) and suggested displaying the alert multiple times yearly for at-risk patients. Another 4 PCPs in the second usability testing session valued the UFHealth-specific alert for managing new or unfamiliar patients, expressed concerns about PCPs' workload when prescribing to high-risk patients, and recommended incorporating the details page into training sessions to enhance usability.

Conclusions: The final backend process for our CDS alert aligns with PCP needs and UFHealth standards. Integrating feedback from PCPs in the early development phase of our ML-driven CDS tool helped identify barriers and facilitators in the CDS integration process. This collaborative approach yielded a refined prototype aimed at minimizing unintended consequences and enhancing usability.

Background: Virtual Reality (VR) is an emerging technology in post stroke recovery. However, its precise role in stroke rehabilitation is not well defined. The aim of this paper is to conduct an overview of systematic reviews on the role of VR in stroke rehabilitation.

Methods: A meta-review with results from a search of 7 databases from inception till 5^th December 2022 with subsequent quality appraisal was conducted. The primary outcome was to produce a narrative review on the efficacy of VR versus usual or other care in stroke recovery. Data was synthesized in a descriptive fashion and high-quality systematic reviews were emphasized. The AMSTAR-2 tool was used for quality assessment of the included studies.

Results: Evidence from high-quality systematic reviews suggests that there is benefit from VR in upper limb, lower limb, gait, and balance recovery particularly when additive to conventional therapy. There is also limited evidence to suggest that VR has a positive effect in those with impaired cognition.

Conclusion: VR is safe and effective as an adjunct to conventional therapy for adults after stroke and should be used routinely for upper and lower limb motor recovery. Further high-quality studies that evaluate its efficacy and explore ways to increase its positive impact in areas such as cognition are required. There is also a scope for the development of stroke-specific virtual environments. (PROSPERO registration # CRD42022372926).

The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.

Nearly all geriatric surgical complications are studied in the context of a single organ system, e.g., cardiac complications and the heart; delirium and the brain; infections and the immune system. Yet, we know that advanced age, physiological stress, and infection all increase sympathetic and decrease parasympathetic nervous system function. Parasympathetic function is mediated through the vagus nerve, which connects the heart, brain, and immune system to form, what we have termed, the brain-heart-immune axis. We hypothesize that this brain-heart-immune axis plays a critical role in surgical recovery among older adults. In particular, we hypothesize that the brain-heart-immune axis plays a critical role in the most common surgical complication among older adults: postoperative delirium. Further, we present heart rate variability as a measure that may eventually become a multi-system vital sign evaluating brain-heart-immune axis function. Finally, we suggest the brain-heart-immune axis as a potential interventional target for bio-electronic neuro-immune modulation to enhance resilient surgical recovery among older adults.

Peripheral neural interfaces facilitate bidirectional communication between the nervous system and external devices, enabling precise control for prosthetic limbs, sensory feedback systems, and therapeutic interventions in the field of Bioelectronic Medicine. Intraneural interfaces hold great promise since they ensure high selectivity in communicating only with the desired nerve fascicles. Despite significant advancements, challenges such as chronic immune response, signal degradation over time, and lack of long-term biocompatibility remain critical considerations in the development of such devices. Here we report on the development and benchtop characterization of a novel design of an intraneural interface based on carbon fiber bundles. Carbon fibers possess low impedance, enabling enhanced signal detection and stimulation efficacy compared to traditional metal electrodes. We provided a 3D-stabilizing structure for the carbon fiber bundles made of PEDOT:PSS hydrogel, to enhance the biocompatibility between the carbon fibers and the nervous tissue. We further coated the overall bundles with a thin layer of elastomeric material to provide electrical insulation. Taken together, our results demonstrated that our electrode possesses adequate structural and electrochemical properties to ensure proper stimulation and recording of peripheral nerve fibers and a biocompatible interface with the nervous tissue.

Bioelectronic Medicine (BEM), which uses implantable electronic medical devices to interface with electrically active tissues, aspires to revolutionize the way we understand and fight disease. By leveraging knowledge from microelectronics, materials science, information technology, neuroscience and medicine, BEM promises to offer novel solutions that address unmet clinical needs and change the concept of therapeutics. This perspective communicates our vision for the future of BEM and presents the necessary steps that need to be taken and the challenges that need to be faced before this new technology can flourish.

Background: Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.

Method: Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.

Results: Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an 'off-disc' stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.

Conclusion: The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in

Background: Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns.

Methods: This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link.

Results: The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation.

Conclusions: The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

Background: Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. Achieving a better understanding of the relationship between VNS parameters and neural and physiological responses is therefore necessary to enable the design of personalized dosing procedures and improve precision and efficacy of VNS therapies.

Methods: We used biomarkers from recorded evoked fiber activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses.

Results: Firstly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Secondly, we describe the relationship between different VNS parameters and the evoked fiber activity and show how spatially selective electrodes can be used to improve fiber recruitment. Thirdly, we provide a detailed exploration of the relationship between the activations of neural fiber types and different physiological effects. Finally, based on these results, we discuss how recordings of evoked fiber activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently.

Conclusion: Understanding of evoked fiber activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.