Faculty Bibliography

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, 49 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, 52 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.

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap-namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing that can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions. OH can be caused by volume depletion, blood loss, cardiac pump failure, large varicose veins, medications, or defective activation of sympathetic nerves and reduced norepinephrine release upon standing. Neurogenic OH is a frequent and disabling problem in patients with synucleinopathies such as Parkinson disease, multiple system atrophy, and pure autonomic failure, and it is commonly associated with supine hypertension. Several therapeutic options are available.

Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body disease, but negative in the frontotemporal dementias (FTDs). Tau PET using the current tracers shows the greatest signal in AD and a lesser signal in FTD. Quantifying volume loss with MRI and measuring metabolism with fluorodeoxyglucose PET helps separate different causes of dementia and follow their progression. Brain inflammation can be assessed with PET. Some of these techniques, still investigational, are likely to find their clinical niche in the near future.

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.

INTRODUCTION/BACKGROUND:The glial-lymphatic pathway is a fluid-clearance pathway consisting of a para-arterial route for the flow of cerebrospinal fluid along perivascular spaces and subsequently toward the brain interstitium. In this case series we aim to investigate an empirical demonstration of glymphatic clearance of extravasated iodine following perforation incurred during endovascular therapy on serial CT. METHODS AND RESULTS/RESULTS:Six consecutive cases of endovascular perforation during thrombectomy performed between 2005 and 2018 were retrospectively collected by searching our internal database of total 446 thrombectomies. Two cases were excluded because care was withdrawn shortly following the procedure and no follow-up imaging was available. One case was excluded because a ventricular drain was placed. Three cases were hence included in this analysis. All three cases demonstrated progressive absorption of contrast by the brain parenchyma with eventual contrast disappearance. CONCLUSION/CONCLUSIONS:We described a likely in vivo CT correlate of the glymphatic system in a cohort of patients who sustained intraprocedural extravasation during thrombectomy for acute ischemic stroke.

The main aim of this study was evaluating the reliability of stimulus-evoked electromyography (using different thresholds for stimulation of the instrumentation devices) for minimally invasive pedicle screw placement in the lumbosacral spine. A threshold of 5 mA was applied for the pedicle access needle. 7 mA was applied for the tapscrew and pedicle screw stimulation. The existence of threshold differences between vertebral levels was also assessed. All patients underwent postoperative computed tomography (CT) to determine the accuracy of pedicle screw placement. A total of 172 percutaneous pedicle screws were placed in 52 patients. 94.1% of screws were placed at L4, L5 and S1 vertebral levels. No statistically significant differences existed in thresholds of the pedicle access needles, tapscrews and pedicle screws between vertebral levels. In four instances, the pedicle access needle stimulation had a threshold of 5 mA (no breaches were associated). In the rest of occasions, the pedicle access needles had stimulation thresholds above 5 mA. In all instances, tapscrew and pedicle screw thresholds were above 7 mA; the tapscrews and pedicle screws had significantly greater thresholds than the pedicle access needles. No statistically significant differences existed in thresholds between tapscrews and pedicle screws. Postoperative CT imaging revealed one lateral pedicle violation. Both breach rate and false negative rate were 0.5%. No false positive cases were observed. No patients experienced postoperative pedicle screw-related neurologic deficits. A threshold of 5 mA for the pedicle access needle stimulation seems to be safe. Greater than 7 mA should be used for the tapscrew and pedicle screw stimulation.