Enhancing biocompatibility of the brain-machine interface: A review.

In vivo implantation of microelectrodes opens the door to studying neural circuits and restoring damaged neural pathways through direct electrical stimulation and recording. Although some neuroprostheses have achieved clinical success, electrode material properties, inflammatory response, and glial scar formation at the electrode-tissue interfaces affect performance and sustainability. Those challenges can be addressed by improving some of the materials' mechanical, physical, chemical, and electrical properties. This paper reviews materials and designs of current microelectrodes and discusses perspectives to advance neuroprosthetics performance.

Safety and Feasibility of an Implanted Inferior Vena Cava Sensor for Accurate Volume Assessment: FUTURE-HF2 Trial.

BACKGROUND: A novel implantable sensor has been designed to accurately measure inferior vena cava (IVC) area to allow daily monitoring of IVC area and collapse to predict congestion in heart failure (HF). METHODS: A prospective, multicenter, single arm, Early Feasibility Study enrolled 15 HF patients (irrespective of ejection fraction) with a HF event in the previous 12 months, an elevated NT-proBNP, and receiving ≥40 mg of furosemide equivalent. Primary endpoints included successful deployment without procedure-related (30 days) or sensor-related complications (three months) and successful data transmission to a secure database (3 months). Accuracy of sensor-derived IVC area, patient adherence, NYHA classification, and KCCQ were assessed from baseline to three months. Patient-specific signal alterations were correlated with clinical presentation to guide interventions. RESULTS: Fifteen patients underwent implantation (66±12 years; 47% female; 27% HFpEF, NT-ProBNP 2569 (median, IQR: (1674-5187)) ng/L; 87% NYHA Class III). All patients met the primary safety and effectiveness endpoints. Sensor-derived IVC area showed excellent agreement with concurrent CT (R2=0.99, mean absolute error=11.15 mm2). Median adherence to daily readings was 98% (IQR: 86-100%) per patient-month. A significant improvement was seen in NYHA class and a non-significant improvement was observed for KCCQ. CONCLUSIONS: Implantation of a novel IVC sensor (FIRE1) was feasible, uncomplicated, and safe. Sensor outputs aligned with clinical presentation and improvements in clinical outcomes. Future investigation to establish the IVC sensor remote management of HF is strongly warranted.

Tricuspid Regurgitation Associated with Implantable Cardiac Devices: A Double-Edged Sword.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; the prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, the management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlights the clinical importance, underlying mechanisms and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Episode-level and clinical characterization of asymptomatic atrial fibrillation events.

INTRODUCTION: Not all patients experience debilitating symptoms during Atrial Fibrillation (AF), some are asymptomatic. The reasons for this inter- and intrasubject variability is unknown. PURPOSE: The study objective was NOAH characterize episode-level and clinical characteristics associated with symptomatic versus asymptomatic episodes of AF in patients with an implantable cardiac monitor (ICM). METHODS: Patients with an AF episode detected on an ICM between 2007 and 2021 with overlapping clinical data from aggregated Electronic Health Records in the Optum® deidentified data set were included. Symptomatic episodes were labeled in real-time by the patient. Heart rate (HR) at onset, mean HR, AF Evidence Score (a measure of beat-to-beat irregularity), episode duration and Activity Index were evaluated for association with symptom status using multivariable regression modeling. RESULTS: 11 267 patients had AF episodes with clinical data available. The 1776 (15.8%) patients who reported symptomatic AF episodes were younger (67 ± 12 years vs. 71 ± 11 years old, p < .001) and had fewer cardiovascular co-morbidities than patients with asymptomatic AF exclusively. Symptomatic episodes were longer (5.5 [2.4, 14.4] h vs. 3.7 [1.7, 11] h, p < .001), had higher mean HR (103 ± 22 bpm vs. 88 ± 22 bpm, p < .001) and higher AF evidence scores (98 ± 27 vs. 82 ± 24, p < .001). These features were independently associated with symptomatic episodes on multivariable regression analysis and per-subject analysis in patients who had both symptomatic and asymptomatic episodes. DISCUSSION: Episode-level characteristics differed between symptomatic AF episodes versus asymptomatic episodes in patients with ICMs. Symptomatic patients also had less comorbidities. These parameters may be useful in understanding variable symptomatic manifestation and remote stratification of AF episodes.

Recent Progress in Artificial Neurons for Neuromodulation.

Driven by the rapid advancement and practical implementation of biomaterials, fabrication technologies, and artificial intelligence, artificial neuron devices and systems have emerged as a promising technology for interpreting and transmitting neurological signals. These systems are equipped with multi-modal bio-integrable sensing capabilities, and can facilitate the benefits of neurological monitoring and modulation through accurate physiological recognition. In this article, we provide an overview of recent progress in artificial neuron technology, with a particular focus on the high-tech applications made possible by innovations in material engineering, new designs and technologies, and potential application areas. As a rapidly expanding field, these advancements have a promising potential to revolutionize personalized healthcare, human enhancement, and a wide range of other applications, making artificial neuron devices the future of brain-machine interfaces.

Brain-implantable needle-type CMOS imaging device enables multi-layer dissection of seizure calcium dynamics in the hippocampus.

Objective: Current neuronal imaging methods mostly use bulky lenses that either impede animal behavior or prohibit multi-depth imaging. To overcome these limitations, we developed a lightweight lensless biophotonic system for neuronal imaging, enabling compact and simultaneous visualization of multiple brain layers.Approach: Our developed 'CIS-NAIST' device integrates a micro-CMOS image sensor, thin-film fluorescence filter, micro-LEDs, and a needle-shaped flexible printed circuit. With this device, we monitored neuronal calcium dynamics during seizures across the different layers of the hippocampus and employed machine learning techniques for seizure classification and prediction.Main results: The CIS-NAIST device revealed distinct calcium activity patterns across the CA1, molecular interlayer, and dentate gyrus. Our findings indicated an elevated calcium amplitude activity specifically in the dentate gyrus compared to other layers. Then, leveraging the multi-layer data obtained from the device, we successfully classified seizure calcium activity and predicted seizure behavior using Long Short-Term Memory and Hidden Markov models.Significance: Taken together, our 'CIS-NAIST' device offers an effective and minimally invasive method of seizure monitoring that can help elucidate the mechanisms of temporal lobe epilepsy.

Evaluating Knee Recovery Beyond Patient Reports: A Comparative Study of Smart Implantable Device-Derived Gait Metrics Versus Patient-Reported Outcome Measures in Total Knee Arthroplasty.

BACKGROUND: Total Knee Arthroplasty (TKA) is frequently performed for advanced osteoarthritis, with patient-reported outcome measures (PROMs) traditionally reporting on efficacy. These subjective evaluations, although useful, may inaccurately reflect post-TKA activity levels. With technological advancements, smart implantable devices (SIDs) offer objective, real-time gait metrics, potentially providing a more accurate postoperative recovery assessment. This study compares these objective metrics with PROMs to evaluate TKA success more effectively. METHODS: We conducted a retrospective cohort study with 88 participants undergoing TKA using a SID. Eligible patients were aged 18 years or older and had advanced osteoarthritis. We excluded those who had bilateral TKAs, joint infections, or neuromuscular disease. The SID system collected daily gait metrics, including step count, distance traveled, walking speed, stride length, cadence, and functional knee range of motion. The PROMs, including Knee Injury and Osteoarthritis Outcome Score-Joint Replacement, Veterans Rand 12 Physical Component Summary, and Veterans Rand 12 Mental Component Summary, were analyzed against SID gait metrics. Among the 88 patients, 80 provided continuous data over 12 weeks. RESULTS: All gait metrics, except stride length, significantly increased at the 12-week point (P < .05). The PROMs also significantly improved postoperatively (P < .05). Initial low positive correlations between 12-week PROMs and SID metrics decreased after adjusting for demographic variables, leaving only weak correlations between the Veterans Rand 12 Physical Component Summary and Knee Injury and Osteoarthritis Outcome Score-Joint Replacement with functional knee range of motion (r = 0.389, P = .002; r = 0.311, P = .014, respectively), and Veterans Rand 12 Mental Component Summary with step count (r = 0.406, P = .001) and distance traveled (r = 0.376, P = .003). CONCLUSIONS: This study indicates that both PROMs and SID gait metrics show significant improvements post-TKA, though they correlate weakly with each other, suggesting a possible discrepancy between perceived recovery and actual functional improvement. The SID gait metrics might provide a valuable addition to traditional PROMs by offering an objective representation of physical capabilities unaffected by patient compliance or subjective perceptions of recovery. Further research is needed to validate these findings in larger populations and to explore whether integrating SID metrics can enhance long-term functional outcomes.

Using artificial intelligence and deep learning to optimise the selection of adult congenital heart disease patients in S-ICD screening.

INTRODUCTION: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening. METHODS: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test. RESULTS: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p < 0.001). There was also a significant difference in the standard deviation of T: R between both groups (p = 0.04). CONCLUSIONS: T:R ratio, a main determinant for S-ICD eligibility, is significantly higher with more tendency to fluctuate in ACHD patients when compared to a population with normal hearts. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio, reducing the risk of TWO and inappropriate shocks in the ACHD patient cohort.

A Novel Intrauterine Device for the Spatio-Temporal Release of Norethindrone Acetate as a Counter-Estrogenic Intervention in the Genitourinary Syndrome of Menopause.

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas-Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

[Treatment with cardiac electronic implantable devices]. / Therapie mit kardialen elektronischen implantierbaren Devices.

Cardiac device therapy provides not only treatment options for bradyarrhythmia but also advanced treatment for heart failure and preventive measures against sudden cardiac death. In heart failure treatment it enables synergistic reverse remodelling and reduces pharmacological side effects. Cardiac resynchronization therapy (CRT) has revolutionized the treatment of reduced left ventricular ejection fraction (LVEF) and left bundle branch block by decreasing the mortality and morbidity with improvement of the quality of life and resilience. Conduction system pacing (CSP) as an alternative method of physiological stimulation can improve heart function and reduce the risk of pacemaker-induced cardiomyopathy. Leadless pacers and subcutaneous/extravascular defibrillators offer less invasive options with lower complication rates. The prevention of infections through preoperative and postoperative strategies enhances the safety of these therapies.