Faculty Bibliography

BACKGROUND/UNASSIGNED:The relationship between early trauma, hyperarousal and aberrant salience has been investigated exclusively in specific clinical samples, such as post-traumatic stress disorder (PTSD) and psychotic patients, and the results suggest that both dimensions are trauma-induced events, which may lead to the later onset, or increase the vulnerability to psychiatric disorders. The aim of the present research was to evaluate the possible relationships among early childhood trauma subtypes and the dimensions of hyperarousal and aberrant salience in an adult sample of psychiatric patients. MATERIALS AND METHODS/UNASSIGNED:One-hundred psychiatric adult outpatients were assessed by Early Trauma Inventory Self Report-Short Form (ETISR-SF), Aberrant Salience Inventory (ASI) and Hyperarousal Scale (H-Scale). A linear regression analysis was performed in order to investigate which early traumatic events were a predictor of the aberrant salience and the hyperarousal. RESULTS/UNASSIGNED: = .031), whereas other ETISR-SF variables did not give a significant additional contribution to the prediction of aberrant salience and the hyperarousal dimension. CONCLUSIONS/UNASSIGNED:These findings support the role of emotional abuse as predictor of hyperarousal, a basic dimension associated with general vulnerability to mental illness. The awareness of the psychiatric consequences of early childhood trauma leads us to consider the need for better identification of children at risk, to develop effective interventions for the protection of minors from violent and/or inappropriate behaviors and to promote the development of protective resilience factors against re-victimization.

Automated production of an fluorine-18 labeled tryptophan analogue, 1-(2-[¹⁸F]fluoroethyl)-l-tryptophan (1-L-[¹⁸F]FETrp) in a current Good Manufacturing Practice facility was achieved. 1-L-[¹⁸F]FETrp was produced by a one-pot, two-step strategy with an overall synthesis time of approximately 100 min, a radiochemical yield of 20 ± 5% (decay corrected), radiochemical purity and enantiomeric excess over 90%, and a molar activity of 103 ± 15 GBq/μmol at the end of synthesis (EOS). The dose mass of 1-L-FETrp in four consecutive batches was less than 5 μg. The radiopharmaceutical product met all quality control criteria for clinical use.

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

Although abnormally folded tau protein has been found to self-propagate from neuron to connected neuron, similar propagation through human brain networks has not been fully documented. We studied tau propagation in the left-hemispheric syntactic network, which is composed of an anterior frontal node and a posterior temporal node, connected by the white matter of the left arcuate fasciculus. This network is affected in non-fluent variant primary progressive aphasia, a neurodegenerative disorder with tau accumulation. Methods: Eight patients with non-fluent variant primary progressive aphasia (age 67.0 ± 7.4 years, 4 women) and eight healthy controls (age 69.6 ± 7.0 years, 4 women) were scanned with ¹⁸F-AV-1451 tau PET, to determine tau deposition in the brain, and with MRI, to determine the fractional anisotropy of the arcuate fasciculus. Normal syntactic network characteristics were confirmed with structural MRI diffusion imaging in our healthy controls and with BOLD functional imaging in 35 healthy participants from the Alzheimer's Disease Neuroimaging Initiative database. Results: Language scores in patients indicated dysfunction of the anterior node. ¹⁸F-AV-1451 deposition was greatest in the two nodes of the syntactic network. The left arcuate fasciculus had decreased fractional anisotropy, particularly near the anterior node. Normal MRI structural connectivity from an area similar to the one containing tau in the anterior, frontal, node projected to an area similar to the one containing tau in the patients, in the posterior, temporal, node. Conclusion: Tau accumulation likely started in the more affected anterior node and, at the stage of the disease when we studied these patients, appeared as well in the brain region, in the temporal lobe, spatially separate but most connected with it. The arcuate fasciculus, connecting both of them, was most severely affected anteriorly, as would correspond to the loss of axons from the anterior node. These findings are suggestive of tau propagation from node to connected node in a natural human brain network and lend support to the idea that neurons that wire together, die together.

The left atrial appendage (LAA) is the most common site of thrombus formation in patients with atrial fibrillation. Therefore, better knowledge of the morphology, physiology, and function of the LAA may provide a better estimate of stroke risk. The LAA morphology is currently classified into 4 categories: chicken-wing (CW), windsock, cauliflower, and cactus. Chicken-wing is the most common and carries lower risk. This classification system, however, lacks consistent inter-rater reliability and correlation with stroke risk.

OBJECTIVES/OBJECTIVE:To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN/METHODS:A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Old age is associated with variability in gait motor output, particularly in females, and is linked to fall risk. However, little is known about how older age and sex affect variability in the outputs of individual joints, and how these variabilities contribute to the collective gait output. Healthy adults aged 18-99 years (N = 102, 57 females) completed six trials of straight walking at self-selected speed. Stride time variability (coefficient of variation) and variabilities of lower limb tridimensional joint angles (standard deviations: SD) were calculated. Age * Sex (A * S) mixed models were conducted on all measures and year-by-year rates of change were subsequently estimated. Correlations and stepwise linear regression analyses were computed between joint angular variabilities and stride time variability. Each year of age was associated with 0.022% higher stride time variability (A: p = .002), 0.07° lower variability in peak ankle dorsiflexion (A: p = .004), 0.002-0.098° higher variability in mean ankle inversion/eversion, mean pelvic obliquity, and pelvic rotation range of motion (A: p < .05), and 0.024° higher variability in knee flexion/extension range of motion in males (A * S: p = .003). Higher variability in mean ankle and hip flexion/extension and in mean ankle inversion/eversion correlated with (ρ = 0.211-0.336; ps < 0.05) and independently predicted higher stride time variability (ps < 0.05), together explaining 21.9% of variance. Results suggest that higher stride time variability with older age may be produced by a shift from sagittal plane variability to frontal plane variability at the ankle.

Severity score represents disease duration-adjusted mean rank of disability in multiple sclerosis (MS) patients from the reference population. This measure allows one to compare the relative rates of disease progression among patients, patient subgroups, and across epochs, which opens up new question of what accounts for the observed differences in severity, and can be used to assess correlation between disease severity and clinical, radiologic, immunologic, genetic, and environmental variables of interest. Severity score can also prove useful for developing prognostic tools in MS. This article discusses the diverse applications of severity score concept in MS research, and (re)introduces Herbert's proposal of severity-based MS classification in the context of variability of MS severity.