Advanced Heart Block and Asystole After Regadenoson Infusion: When Cautionary Tales Become Reality.

Regadenoson (brand name Lexiscan) is a specific adenosine receptor agonist commonly used in pharmacologic stress testing due to its coronary vasodilatory effects. Despite it being generally well-tolerated, the American Society of Nuclear Cardiology established absolute and relative contraindications to the use of regadenoson in patients with certain co-morbidities such as uncontrolled hyper/hypotension, sinus node disease, and second-degree heart blocks. While cases of advanced heart block after the administration of regadenoson have been reported, they remain incidental. We report the case of an 84-year-old male sustaining second-degree type II heart block, followed by pulseless electrical activity and asystole after the administration of regadenoson.

Infraclavicular de novo placement of a responsive neurostimulator for a patient with eloquent glioma-associated epilepsy: illustrative case.

BACKGROUND: The authors present a 50-year-old female with high-grade glioma involving the motor cortex as the cause of her drug-resistant epilepsy (DRE). Responsive neurostimulation (RNS) was chosen for epilepsy treatment. Due to concerns regarding the generator impeding the regular imaging surveillance required for treatment and monitoring of her glioma, surgeons placed the internal pulse generator (IPG) within an infraclavicular chest pocket. OBSERVATIONS: Implantation of the RNS device and IPG within the infraclavicular pocket was uneventful. However, both subdural and depth electrodes were used and connected to the IPG, and subdural electrodes are considerably shorter than depth electrodes (37 vs 44 cm). The shorter strip leads presumably generated significant tension, leading to fracture of the leads. Therefore, surgery was repeated using only depth electrodes for more length and less tension. The device has good-quality electrocorticography signals that continue to be used for device programming. The seizure burden was reduced, and quality of life improved for the patient. LESSONS: The RNS system with infraclavicular IPG placement reduced the seizure burden and improved the quality of life of a patient with glioma-associated epilepsy. Surgeons may consider the infraclavicular location as an alternative site for implantation for RNS candidates who require recurrent intracranial magnetic resonance imaging.

A Web- and Mobile-Based Intervention for Women Treated for Breast Cancer to Manage Chronic Pain and Symptoms Related to Lymphedema: Results of a Randomized Clinical Trial.

BACKGROUND: The-Optimal-Lymph-Flow (TOLF) is a patient-centered, web- and mobile-based mHealth system that delivers safe, easy, and feasible digital therapy of lymphatic exercises and limb mobility exercises. OBJECTIVE: The purpose of this randomized clinical trial (RCT) was to evaluate the effectiveness of the web- and mobile-based TOLF system for managing chronic pain and symptoms related to lymphedema. The primary outcome includes pain reduction, and the secondary outcomes focus on symptom relief, limb volume difference measured by infrared perometer, BMI, and quality of life (QOL) related to pain. We hypothesized that participants in the intervention group would have improved pain and symptom experiences, limb volume difference, BMI, and QOL. METHODS: A parallel RCT with a control-experimental, pre- and posttest, and repeated-measures design were used. A total of 120 patients were recruited face-to-face at the point of care during clinical visits. Patients were randomized according to pain in a 1:1 ratio into either the arm precaution (AP) control group to improve limb mobility and arm protection or The-Optimal-Lymph flow (TOLF) intervention group to promote lymph flow and limb mobility. Trial outcomes were evaluated at baseline and at week 12 after the intervention. Descriptive statistics, Fisher exact tests, Wilcoxon rank-sum tests, t test, and generalized linear mixed effects models were performed for data analysis. RESULTS: At the study endpoint of 12 weeks, significantly fewer patients in the TOLF intervention group compared with the AP control group reported chronic pain (45% [27/60] vs 70% [42/60]; odds ratio [OR] 0.39, 95% CI 0.17-0.90; P=.02). Patients who received the TOLF intervention were significantly more likely to achieve a complete reduction in pain (50% [23/46] vs 22% [11/51]; OR 3.56, 95% CI 1.39-9.76; P=.005) and soreness (43% [21/49] vs 22% [11/51]; OR 2.60, 95% CI 1.03-6.81; P=.03). Significantly lower median severity scores were found in the TOLF group for chronic pain (MedTOLF=0, IQR 0-1 vs MedAP=1, IQR 0-2; P=.02) and general bodily pain (MedTOLF=1, IQR=0-1.5 vs MedAP=1, IQR 1-3; P=.04). Compared with the AP control group, significantly fewer patients in the TOLF group reported arm/hand swelling (P=.04), heaviness (P=.03), redness (P=.03), and limited movement in shoulder (P=.02) and arm (P=.03). No significant differences between the TOLF and AP groups were found in complete reduction of aching (P=.12) and tenderness (P=.65), mean numbers of lymphedema symptom reported (P=.11), ≥5% limb volume differences (P=.48), and BMI (P=.12). CONCLUSIONS: The TOLF intervention had significant benefits for breast cancer survivors to manage chronic pain, soreness, general bodily pain, arm/hand swelling, heaviness, and impaired limb mobility. The intervention resulted in a 13% reduction (from 40% [24/60] to 27% [16/60]) in proportions of patients who took pain medications compared with the AP control group, which had a 5% increase (from 40% [24/60] to 45% [27/60]). A 12% reduction (from 27% [16/60] to 15% [9/60]) in proportions of patients with ≥5% limb volume differences was found in the TOLF intervention, while a 5% increase in the AP control group (from 40% [24/60] to 45% [27/60]) was found. In conclusion, the TOLF intervention can be a better choice for breast cancer survivors to reduce chronic pain and limb volume. TRIAL REGISTRATION: Clinicaltrials.gov NCT02462226; https://clinicaltrials.gov/ct2/show/NCT02462226. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.5104.

Assessment of the Effects of Altered Amyloid-Beta Clearance on Behavior following Repeat Closed-Head Brain Injury in Amyloid-Beta Precursor Protein Humanized Mice.

Traumatic brain injury (TBI) increases the risk for dementias including Alzheimer's disease (AD) and chronic traumatic encephalopathy. Further, both human and animal model data indicate that amyloid-beta (Aß) peptide accumulation and its production machinery are upregulated by TBI. Considering the clear link between chronic Aß elevation and AD as well as tau pathology, the role(s) of Aß in TBI is of high importance. Endopeptidases, including the neprilysin (NEP)-like enzymes, are key mediators of Aß clearance and may affect susceptibility to pathology post-TBI. Here, we use a "humanized" mouse model of Aß production, which expresses normal human amyloid-beta precursor protein (APP) under its natural transcriptional regulation and exposed them to a more clinically relevant repeated closed-head TBI paradigm. These transgenic mice also were crossed with mice deficient for the Aß degrading enzymes NEP or NEP2 to assess models of reduced cerebral Aß clearance in our TBI model. Our results show that the presence of the human form of Aß did not exacerbate motor (Rotarod) and spatial learning/memory deficits (Morris water maze) post-injuries, while potentially reduced anxiety (Open Field) was observed. NEP and NEP2 deficiency also did not exacerbate these deficits post-injuries and was associated with protection from motor (NEP and NEP2) and spatial learning/memory deficits (NEP only). These data suggest that normally regulated expression of wild-type human APP/Aß does not contribute to deficits acutely after TBI and may be protective at this stage of injury.

Lentiviral Delivery of miR-133b Improves Functional Recovery After Spinal Cord Injury in Mice.

Based on the observation that microRNA (miRNA) 133b enhances regeneration after spinal cord injury in the adult zebrafish, we investigated whether this miRNA would be beneficial in a mammalian system in vitro and in vivo. We found that infection of cultured neurons with miR-133b promotes neurite outgrowth in vitro on an inhibitory substrate consisting of mixed chondroitin sulfate proteoglycans, when compared to infection with green fluorescent protein (GFP) for control. In vivo, viral infection of the injured adult mouse spinal cord at the time of injury at and in the vicinity of the lesion site enhanced expression of miR-133b. Measurements of locomotor recovery by Basso Mouse Scale (BMS) showed improvement of recovery starting at 4 weeks after injury and virus injection. This improvement was associated with downregulation of the expression levels of Ras homolog gene family member A (RhoA), chondroitin sulfate proteoglycans, and microglia/macrophage marker in the spinal cord as assayed 6 weeks after injury. Potential inhibitory molecules carrying consensus sequences for binding of miR-133b were identified in silico and verified in a reporter assay in vitro showing reductions in expression of RhoA, xylosyltransferase 1 (Xylt1), ephrin receptor A7 (Epha7), and purinergic receptor P2X ligand-gated ion channel 4 (P2RX4). These results encourage targeting miR-133 for therapy.