The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala

We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.This work was conducted within the Behavioural and Clinical Neuroscience Institute, a joint initiative funded by the Wellcome Trust and the UK Medical Research Council, in the Department of Psychology at the University of Cambridge. This work was funded by a UK Medical Research Council programme grant (no. G1002231) awarded to BJE and ALM. PR was supported by a Department of Physiology and Pharmacology Fellowship at the Sapienza University of Rome, and an Italian Society of Pharmacology Fellowship. ALM is the Ferreras-Willetts Fellow in Neuroscience at Downing College, Cambridge. The manuscript was partly prepared while ALM was an Erskine Visiting Cambridge Fellow at the University of Canterbury, Christchurch, New Zealand

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Complex Lemierre syndrome with multisystemic abscesses.

We present here the challenging case of severe Lemierre syndrome in a healthy woman in her late twenties, whose clinical presentation was characterised by lung abscesses and disseminated systemic abscesses in the brain, the abdomen and the soft-tissues, as a likely consequence of a patent foramen ovale. Blood cultures were positive for Fusobacterium necrophorum and a right lingual vein thrombosis was detected at a late stage when the patient developed a septic shock. Initial antimicrobial therapy with metronidazole and ceftriaxone was modified to meropenem due to progressive worsening. The patient underwent laparoscopy and neurosurgical drainage of a cerebral abscess. She spent many days in the intensive care unit and recovered fully after 6 weeks on meropenem therapy. Although considered rare, the incidence of Lemierre syndrome, a potentially life-threatening condition, is increasing. The clinician should promptly recognise and treat it while being aware of its potential atypical presentations

Agreement between activated partial thromboplastin time and anti-Xa activity in critically ill patients receiving therapeutic unfractionated heparin.

No study supports the use of either aPTT or anti-Xa activity for heparin monitoring in critical care patients. There are no strong data on the agreement between aPTT and anti-Xa. The aims of this study were to: 1. Analyse the agreement between aPTT and anti-Xa in a large population of critically ill patients under unfractionated heparin therapy (UFH), 2. Identify clinical and biological factors associated to agreement or disagreement, and 3. Analyse the impact of anti-Xa availability on the use of aPTT and UFH therapy. Retrospective study in a 35 beds mixed-ICU population between 2006 and 2016 in a University teaching hospital. delivery of a UFH dose >15,000 U/24 h during at least one day with one anti-Xa determination. demographic variables, aPTT, anti-Xa, laboratory variables, presence of extracorporeal devices (ECD). Pairs of simultaneously dosed aPTT and anti-Xa [aPTT:anti-Xa] were analysed on the basis of their agreement within the sub-therapeutic, therapeutic (aPTT 50-80″, anti-Xa 0.3-0.7 U/ml) or supra-therapeutic ranges. 2283 patient admissions (2085 patients) were analysed. 35,595 [aPTT:anti-Xa] pairs were found. The overall [aPTT:anti-Xa] agreement was 59.6% and lowest (54.3%) in presence of ECD compared to non-ECD patients (61.6%; p < 0.001). Sixteen demographic and biological variables were analysed and were not predictive of [aPTT:anti-Xa] agreement. No significant difference in administered UFH dose was observed after anti-Xa introduction. In this large cohort, the [aPTT:anti-Xa] agreement is <60% and significantly lower in patients with ECD. None of the variables identified as potentially affecting the agreement were predictive. Availability of anti-Xa had neither effect on aPTT use nor on UFH-dose. These results call for a prospective study to determine the optimal UFH-therapy monitoring tool

2021 ELSO Adult and Pediatric Anticoagulation Guidelines.

These guidelines for adult and pediatric anticoagulation for extracorporeal membrane oxygenation are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines

Impact of a Dedicated Noninvasive Ventilation Team on Intubation and Mortality Rates in Severe COPD Exacerbations.

BACKGROUND: Compared with usual care, noninvasive ventilation (NIV) lowers the risk of intubation and death for subjects with respiratory failure secondary to COPD exacerbations, but whether administration of NIV by a specialized, dedicated team improves its efficiency remains uncertain. Our aim was to test whether a dedicated team of respiratory therapists applying all acute NIV treatments would reduce the risk of intubation or death for subjects with COPD admitted for respiratory failure. METHODS: We carried out a retrospective study comparing subjects with COPD admitted to the ICU before (2001-2003) and after (2010-2012) the creation of a dedicated NIV team in a regional acute care hospital. The primary outcome was the risk of intubation or death. The secondary outcomes were the individual components of the primary outcome and ICU/hospital stay. RESULTS: A total of 126 subjects were included: 53 in the first cohort and 73 in the second. There was no significant difference in the demographic characteristics and severity of respiratory failure. Fifteen subjects (28.3%) died or had to undergo tracheal intubation in the first cohort, and only 10 subjects (13.7%) in the second cohort (odds ratio 0.40, 95% CI 0.16-0.99, P = .04). In-hospital mortality (15.1% vs 4.1%, P = .03) and median stay (ICU: 3.1 vs 1.9 d, P = .04; hospital: 11.5 vs 9.6 d, P = .04) were significantly lower in the second cohort, and a trend for a lower intubation risk was observed (20.8% vs 11% P = .13). CONCLUSIONS: The delivery of NIV by a dedicated team was associated with a lower risk of death or intubation in subjects with respiratory failure secondary to COPD exacerbations. Therefore, the implementation of a team administering all NIV treatments on a 24-h basis should be considered in institutions admitting subjects with COPD exacerbations

Cement augmentation for trochanteric fracture in elderly: A systematic review

Background: Cement augmentation of internal fixation of hip fracture has reported to improve fracture stability in osteoporotic hip fractures, reducing the risk of cut-out of the sliding screw through the femoral head. The purpose of present study was to perform a systematic literature review on the effects of augmentation technique in patients with osteoporotic hip fractures. Material and methods: A comprehensive literature search was systematically performed to evaluate all papers published in English language included in the literature between January 2010 and July 2020, according to the PRISMA 2009 guidelines. In vivo and in vitro studies, case reports, review articles, cadaveric studies, biomechanical studies, histological studies, oncological studies, technical notes, studies dealing with radiological classifications and studies on revision surgery were excluded. Results: A total of 5 studies involving 301 patients were included. Patients had a mean age of 84.6 years and were followed up for a mean period of 11 months. The proximal femoral fractures were stabilized with implantation of the PFNA or Gamma nail and augmentation was performed with two different cements: polymethylmethacrylate (PMMA) in 4 studies and calcium phosphate (CP) in one study. Overall, 57.5% of patients reached the same or greater preoperative mobility, and postoperative Parker Mobility Score and Harris Hip Score were acceptable. No significantly complications were observed, and no additional surgery related to the implant was required. Conclusion: The results of this systematic review show that cement augmentation is a safe and effectiveness method of fixation to treat trochanteric fractures