Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

Effects of metformin on recognition memory and hippocampal neuroplasticity in rats with metabolic syndrome

Metabolic syndrome (MS) is a health problem that is characterized by body fat accumulation, hypertension, dyslipidemia, and hyperglycemia; recently, it has been demonstrated that MS also damages memory processes. The first-line drug in the treatment of MS and type 2 diabetes mellitus is metformin, which is an antihyperglycemic agent. This drug has been shown to produce neuroprotection and to improve memory processes. However, the mechanism involved in this neuroprotection is unknown. A 90-day administration of metformin improved the cognitive processes of rats with MS as evaluated by the novel object recognition test, and this finding could be explained by an increase in the neuronal spine density and spine length. We also found that metformin increased the immunoreactivity of synaptophysin, sirtuin-1, AMP-activated protein kinase, and brain-derived neuronal factor, which are important plasticity markers. We conclude that metformin is an important therapeutic agent that increases neural plasticity and protects cognitive processes. The use of this drug is important in the minimization of the damage caused by MS.     

Prevalence and impact of insomnia in children and adolescents with body dysmorphic disorder undergoing multimodal specialist treatment

European Child & Adolescent Psychiatry - Pediatric body dysmorphic disorder (BDD) is challenging to treat. This study aimed to establish the prevalence of insomnia in youth with BDD and explore...     

Prediction of Learned Resistance or Helplessness by Hippocampal-Prefrontal Cortical Network Activity during Stress

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (PFC) and the hippocampus (HPC) are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded HPC and PFC neural activities in male rats during the exposure to controllable, uncontrollable, or no shocks and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from nonstressed animals and predict resistant (R) or helpless (H) individuals based on hippocampal-cortical oscillatory dynamics. Remarkably, R animals exhibited an increase in theta power during CS, while H exhibited a decrease. Furthermore, R exhibited higher HPC to PFC θ synchronization during stress. Notably, HPC-PFC θ connectivity in the initial stress exposure showed strong correlations with escape performance evaluated days later. R rats also showed stronger θ coupling to both γ oscillations and neuronal firing in the PFC. Finally, we found that these distinct features of network dynamics collectively formed a pattern that accurately predicted learned resistance and was lacking in H individuals. Our findings suggest that hippocampal-prefrontal network θ activity supports cognitive mechanisms of stress coping, whose impairment may underlie vulnerability to stress-related disorders.SIGNIFICANCE STATEMENT The appraisal of adversities as controllable or uncontrollable is key in determining resilience or risk for stress-related disorders. Here, we performed the first electrophysiological investigation during controllable or uncontrollable stress. Pharmacological studies showed that the prefrontal cortex (PFC) and the hippocampus (HPC) encode stressor controllability, and here we identified the neural activity underlying this process. This “neural signature of stressor controllability” accurately predicted resistance to future stressors and was characterized by increased HPC-PFC oscillatory activity in the θ frequency (4–10 Hz). Our findings suggest a new role of frontal θ oscillations in adaptive stress coping, integrating its emotional and cognitive functions. We also endorse the potential of this biomarker to guide neurophysiologically-informed and rhythm-based stimulation therapies for depression.     

The anatomical and radiological evaluation of the Vidian canal on cone-beam computed tomography images

European Archives of Oto-Rhino-Laryngology - The aim of this study is to explore the anatomy of the Vidian nerve to elucidate the appropriate surgical approach based on preoperative cone-beam...     

Sonication did not provide reliability to Maki technique for catheter related bloodstream infection diagnosis

ObjectiveThe aim of our study was to analyze sonication and Maki techniques for diagnosis of catheter tip colonization and catheter-related bloodstream infection (CRBSI) on patients admitted to ICU.Material and methodsObservational and prospective study in one Intensive Care Unit. Patients with some central venous catheter (CVC) at least for 7 days and catheter-related infection (CRI) suspicion (new episode of fever or sepsis) were included. We performed Maki technique followed by sonication of catheter tip. We compared area under the curve (AUC) of Maki, sonication, and techniques combination to diagnosis catheter tip colonization and CRBSI.ResultsWe included 94 CVC from 87 CRI suspicion episodes. We found 14 cases of catheter tip colonization and 10 cases of CRBSI. Of the 14 catheter tip colonization cases, 7 (50.0%) were detected by Maki and sonication techniques, 6 (42.9%) were detected only by Maki technique, and 1 (7.1%) was detected only by sonication technique. Of the 10 CRBSI, 6 (60.0%) were detected by Maki and sonication techniques, 4 (40.0%) were detected only by Maki technique, and any only by sonication technique. We found higher AUC in Maki technique than in sonication technique to diagnosis of CRBSI (p=0.02) and to diagnosis of catheter tip colonization (p=0.03). No significant differences were found in AUC between Maki technique and combination techniques for diagnosis of catheter tip colonization (p=0.32) and of CRBSI (p=0.32).Conclusion.:Sonication did not provide reliability to Maki technique for diagnosis of catheter tip colonization and CRBSI.     

Epidemiological Review of Spinal Cord Injury due to Road Traffic Accidents in Latin America

Spinal cord injury (SCI) is a disease that affects the normal function of the spinal cord. Road traffic accidents (RTAs) represent the main cause of SCI worldwide. SCI may generate physical disability and economic dependency, which is especially significant in low- and middle-income countries such as most of the Latin American countries. The main objective of this study was to present an epidemiological review of SCI secondary to RTAs. Stronger evidence on this condition in Latin America is important for future-specific data collection and prevention strategies. A literature review was carried out using specific search strategies in databases of indexed journals from the period 2000 to 2019. Data on SCI secondary to RTAs in the Latin American region were collected and analyzed. After initial screening and removal of duplicates, 16 articles met the inclusion criteria and were chosen for analysis. Data from 7 Latin American countries were retrievable. On average, RTAs were responsible for 40.81% of SCI. Data from different studies are heterogeneous. Car accidents and moto accidents were equally responsible for SCIs (50.61% vs. 49.06%). The thoracic segments were the most commonly affected (57.87%). Males in their 30s were the most affected category (76.6%). SCI due to RTAs may represent a severe but preventable condition that affects mostly men in their productive age, generating important social and economic issues. Data about this condition in Latin America are scarce, and could limit prevention and treatment strategies. Prospective data collection about this condition is recommended.