Sensory computations in the cuneate nucleus of macaques

Tactile nerve fibers fall into a few classes that can be readily distinguished based on their spatiotemporal response properties. Because nerve fibers reflect local skin deformations, they individually carry ambiguous signals about object features. In contrast, cortical neurons exhibit heterogeneous response properties that reflect computations applied to convergent input from multiple classes of afferents, which confer to them a selectivity for behaviorally relevant features of objects. The conventional view is that these complex response properties arise within the cortex itself, implying that sensory signals are not processed to any significant extent in the two intervening structures-the cuneate nucleus (CN) and the thalamus. To test this hypothesis, we recorded the responses evoked in the CN to a battery of stimuli that have been extensively used to characterize tactile coding in both the periphery and cortex, including skin indentations, vibrations, random dot patterns, and scanned edges. We found that CN responses are more similar to their cortical counterparts than they are to their inputs: CN neurons receive input from multiple classes of nerve fibers, they have spatially complex receptive fields, and they exhibit selectivity for object features. Contrary to consensus, then, the CN plays a key role in processing tactile information

Long-Term Outcome of Single-Chamber Atrial Pacing Compared with Dual-Chamber Pacing in Patients with Sinus-Node Dysfunction and Intact Atrioventricular Node Conduction

∙The authors have no financial conflicts of interest. Purpose: The optimal pacing mode with either single chamber atrial pacemaker (AAI or AAIR) or dual chamber pacemaker (DDD or DDDR) is still not clear in sinus-node dysfunction (SND) and intact atrioventricular (AV) conduction. Materials and Methods: Patients who were implanted with permanent pacemaker using AAI(R) (n = 73) or DDD(R) (n = 113) were compared. Results: The baseline characteristics were comparable between the two groups, with a mean follow-up duration of 69 months. The incidence of death did not show statistical difference. However, the incidence of hospitalization for congestive heart failure (CHF) was significantly lower in the AAI(R) group (0%) than the DDD(R) group (8.8%, p = 0.03). Also, atrial fibrillation (AF) was found in 2.8 % in the AAI(R) group, which was statistically different from 15.2 % of patients in the DDD(R) group (p = 0.01). Four patients (5.5%) with AAI(R) developed AV block, and subsequently switched to DDD(R) pacing. The risk of AF was lower in the patients implanted with AAI(R

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded – in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands – the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger’s movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction

BACKGROUND Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P CONCLUSIONS In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial.

The aim of this study was to determine the lowest optimal tissue plasminogen activator (tPA) dose and delivery duration using ultrasound-facilitated catheter-directed thrombolysis (USCDT) for the treatment of acute intermediate-risk (submassive) pulmonary embolism.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Paradoxical pulmonary artery systolic pressure response with catheter-directed therapies for pulmonary embolism

Background: Early data on use of catheter-directed therapies (CDT) for treatment of Intermediate or High-Risk pulmonary embolism (PE) show improvement in pulmonary artery systolic pressures (PAsP) and RV/LV ratios. Occasionally a paradoxical rise in PAsP was observed with CDT utilizing ultrasound-assisted thrombolysis (USAT). It is unclear whether this pattern is seen with CDT utilizing mechanical aspiration. Objectives: To investigate and compare the changes in PAsP between those who underwent CDT with USAT to those with mechanical aspiration. Methods: A retrospective analysis of those diagnosed with Intermediate or High-Risk PE who underwent CDT using USAT or mechanical aspiration from 7/2013 to 3/2023. The primary outcome was comparison of PAsP changes between the two modalities. Secondary outcomes include length of stay, mortality, and bleeding complications. Results: A total of 142 patients were analyzed, of which 93 underwent USAT and 49 underwent mechanical thrombectomy. The mechanical thrombectomy group had significantly lower post-intervention PAsP than the USAT group (42.2 ± 13.4 mmHg vs 54.5 ± 15.2 mmHg, p < 0.0001) and a greater adjusted mean reduction (−16.5 ± 2.7 vs. −7.7 ± 3.2 mmHg. p < 0.0001). A higher frequency of a paradoxical rise in PAsP was observed in the USAT group (22 % vs 4.1 %, p < 0.001). Conclusions: CDT utilizing mechanical thrombectomy was associated with lower post-interventional PAsP and greater mean negative change compared to USAT. Occasional paradoxical rises in PAsP were observed with both types of CDT, but they were more frequent with USAT. Hemodynamic monitoring should be considered after CDT. Condensed unstructured abstract: We report a retrospective comparison of changes to pulmonary artery systolic pressures (PAsPs) between catheter-directed ultrasound-assisted thrombolysis (USAT) and catheter-directed mechanical thrombectomy in Intermediate and High-Risk pulmonary embolism. Those treated with mechanical thrombectomy compared to USAT had significantly lower post-interventional PAsP (42.2 ± 13.4 mmHg vs 54.5 ± 15.2 mmHg, p < 0.0001) and a greater adjusted mean reduction (−16.2 ± 2.7 vs. −7.5 ± 3.2 mmHg, p < 0.0001). A paradoxical rise in PAsP was observed more frequently in the USAT group than the mechanical thrombectomy group (22 % vs 4.1 %, p < 0.001)

Submassive Pulmonary Embolism: The Impact of Early Clot Reduction with Ultrasound-Accelerated Thrombolysis on Pulmonary Hypertension

Rationale: Submassive pulmonary embolism (PE) is an established risk factor for the development of chronic thromboembolic pulmonary hypertension (CTEPH), particularly when the initial pulmonary artery systolic pressure (PASP) is \u3e50 mmHg. Ultrasound-accelerated thrombolysis (USAT) rapidly reduces clot burden in submassive PE. We investigated the impact of early clot reduction by USAT on pulmonary hypertension following submassive PE. Methods: Patients with acute submassive PE treated with concurrent intravenous unfractionated herapin and USAT with the EkoSonic MACH4e Endovascular System (EKOS Corporation, Bothwell, WA) were retrospectively studied. PE was diagnosed by CT angiography (CTA). Submassive was defined as right ventricular dysfunction (RVD) with hemodynamic stability. RVD criteria included a combination of: Right Ventricular/Left Ventricular (RV/LV) diameter ratio on CTA \u3e1.0, RV systolic dysfunction or estimated PASP\u3e50 mmHg by transthoracic echocardiogram, and elevated troponin I or brain-type natriuretic peptide. TPA dose was 0.5 mg/hr/catheter for bilateral USAT (unilateral: 1.0 mg/hr). Pulmonary artery pressure (PAP) was obtained during catheterization immediately pre/post-USAT. Targeted activated partial thromboplastin time during USAT was 40-60 seconds. Clot burden was assessed by the Miller index, calculated by two independent observers. utilizing arteriography. Safety outcomes were assessed. Results: Nineteen patients (9 men, 10 female; age 36±18) were identified. Eighteen patients underwent bilateral USAT. Mean tPA infusion time was 22 hours. Mean RV/LV ratio was 1.37. Clot burden was reduced by 72% (Miller index 18±3 to 5±2; p\u3c0.0001). Mean PAP decreased by 6 mmHg (40 mmHg±9 to 34 mmHg±9; p\u3c0.0029). A subgroup (n=5) was identified who despite a 76% reduction in clot burden, mean PAP did not change at 23 hours. Furthermore, 3/12 patients with initial PASP\u3e50 mmHg showed no change in PAP after USAT and on follow-up. No bleeding complications occurred. Conclusions: USAT with continuous herapin proved safe and effective in reducing clot burden at 22 hours. Pulmonary hypertension was reduced in a majority of cohort; however, one fourth of the patients had no improvement in mean PAP despite over 70% clot burden reduction. this finding suggests factors other than thrombotic obstruction, such as pre-existing CTEPH, other causes of PH, or vasoconstriction may be driving PH association with submassive PE. Lack of hemodynamic improvement despite clot reduction immediately following USAT may identify patients at risk for or pre-existing CTEPH. Long-term follow-up is essential to evaluate the impact of USAT on the development of CTEPH

High Intermediate Risk Pulmonary Embolism: The Use of Very Low Dose Catheter-Directed Ultrasound- Accelerated Thrombolysis

Objective: To determine the hemodynamic benefit, clot burden reduction and safety utilizing an ultra-low dose of Tissue Plasminogen Activator (TPA) with Catheter directed Ultrasound accelerated thrombolysis (USAT) in the management of high Intermediate Risk Pulmonary Embolism.Design: Retrospective, observational case series.Setting: Single Center Academic Community Hospital.Patients: Fifty-two consecutive patients (27 males) with high Intermediate Risk PE treated with USAT were analyzed.Measurements and Main Results: Forty-nine patients underwent bilateral USAT with 0.5 mg/hr/catheter of TPA (unilateral: 1.0 mg/hr). Mean duration of therapy was 22.08 + 4.90 hours. Changes in pulmonary artery pressure (PAP), Clot obstruction index by Miller score and procedure related bleeding complications were assessed. Paired t-testing was used to determine significance Mean RV/LV ratio was 1.52 + 0.36. Miller score decreased 55.0% (mean 19.7 + 3.8 to 8.9 + 4.7; p value \u3c 0.0001). The systolic PAP decreased 7.3% from 63.6 + 15.1 mmHg to 59.0 + 17.5 mmHg (p value = 0.0045). The mean PAP decreased 5.4% from 37.5 + 8.0 mmHg to 35.5 + 9.1 mmHg (p value = 0.0097). No procedural or bleeding related complications occurred.Conclusion: Low dose USAT with 0.5mg/hr/catheter with TPA for 24 hours is highly effective in reducing clot burden and PAP without bleeding or procedural related complications in high Intermediate Risk PE