Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease.

OBJECTIVE: To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF ß-amyloid (Aß)42/Aß40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). METHODS: CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aß42, Aß40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. RESULTS: Age and lower Aß42/Aß40 were independently associated with elevated p-tau181. Age, Aß42/Aß40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aß42/Aß40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aß42 was not significantly associated with p-tau181 or memory. CONCLUSIONS: Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases.

PURPOSE: In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). METHODS: Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aß+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. RESULTS: SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aß+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. CONCLUSION: Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

A Case of COVID-19 Pneumonia in a Young Male with Full Body Rash as a Presenting Symptom.

BACKGROUND: In December 2019 the coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, was identified in Wuhan, China. In the ensuing months, the COVID-19 pandemic has spread globally and case load is exponentially increasing across the United States. Emergency departments have adopted screening and triage procedures to identify potential cases and isolate them during evaluation. CASE PRESENTATION: We describe a case of COVID-19 pneumonia requiring hospitalization that presented with fever and extensive rash as the primary presenting symptoms. Rash has only been rarely reported in COVID-19 patients, and has not been previously described.

Use of ECMO support in pediatric patients with severe thoracic trauma.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used in the non-trauma setting for over 30 years. However, the use of ECMO in trauma remains a difficult question, as the risk of bleeding must be weighed against the benefits of cardiopulmonary support. METHODS: Retrospective review of children who sustained severe thoracic trauma (chest abbreviated injury score ≥3) and required ECMO support between 2009 and 2016. RESULTS: Of the 425 children who experienced severe thoracic trauma, 6 (1.4%) underwent ECMO support: 67% male, median age 4.8 years, median ISS 36, median GCS 3, and overall survival 83%. The median hospital day of ECMO initiation was 2 with a median ECMO duration of 7 days. All cannulations occurred through the right neck regardless of the size of the child. Five initially had veno-venous support with 1 requiring conversion to veno-arterial (VA) support. Both children on VA support suffered devastating cerebrovascular accidents, one of which ultimately led to withdrawal of care and death. Complications in the cohort included: paraplegia (1), neurocognitive defects/dysphonia (1), infected neck hematoma (1), deep femoral venous thrombosis (1), bilateral lower extremity spasticity (1). CONCLUSION: This small cohort supports the use of ECMO in children with severe thoracic injuries as a potentially lifesaving intervention, however, not without significant complication. LEVEL OF EVIDENCE: IV.

Weight-Based Dosing for Once-Daily Enoxaparin Cannot Provide Adequate Anticoagulation for Venous Thromboembolism Prophylaxis.

BACKGROUND: Surgeons commonly provide enoxaparin prophylaxis to high-risk patients to decrease venous thromboembolism risk. The authors' prior work demonstrated that most patients receive inadequate venous thromboembolism prophylaxis, based on anti-factor Xa level, when enoxaparin 40 mg/day is provided and that peak anti-factor Xa level correlates with weight. This study models a weight-based strategy for daily enoxaparin prophylaxis and its impact on anti-factor Xa levels. METHODS: The authors enrolled plastic surgery patients who received enoxaparin 40 mg/day and had anti-factor Xa levels drawn. The enoxaparin dose of 40 mg was converted to a milligram-per-kilogram dose for each patient. Stratified analysis examined the milligram-per-kilogram dose that produced low, in-range, and high anti-factor Xa levels to identify the appropriate milligram-per-kilogram dose to optimize venous thromboembolism prevention and bleeding events. RESULTS: Among 94 patients, weight-based dosing ranged from 0.28 to 0.94 mg/kg once daily. For peak and trough anti-factor Xa levels, there was nearly complete overlap for milligram-per-kilogram dosing that produced low versus in-range anti-factor Xa levels. For peak anti-factor Xa, there was nearly complete overlap for milligram-per-kilogram dosing that produced in-range versus high anti-factor Xa levels. Mean milligram-per-kilogram dose was not significantly different between patients who did or did not have postoperative venous thromboembolism (0.41 mg/kg versus 0.52 mg/kg; p = 0.085) or clinically relevant bleeding (0.48 mg/kg versus 0.51 mg/kg; p = 0.73). CONCLUSIONS: Alterations in enoxaparin dose magnitude based on patient weight cannot allow a high proportion of patients to achieve appropriate anti-factor Xa levels when once-daily enoxaparin prophylaxis is provided. Future research should examine the impact of increased enoxaparin dose frequency on anti-factor Xa levels, venous thromboembolism events, and bleeding. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The utility of a "trauma 1 OP" activation at a level 1 pediatric trauma center.

PURPOSE: To expedite flow of injured children suspected to require operative intervention, a "trauma 1 OP" (T1OP) activation classification was created. The purpose of this study was to review this strategy at a level 1 pediatric trauma center. METHODS: A retrospective review of T1OP activations between 2003 and 2015 was performed. Children suspected of requiring neurosurgical intervention were classified as trauma 1 OP neuro (T1OP(N)). Comparisons were made to trauma 1 (T1) patients who required emergent operative intervention, excluding orthopedic injuries. RESULTS: Overall, 461 T1OP activations occurred (72% T1OP(N)) compared to 129 T1 activations requiring emergent surgery. Demographics were not significantly different between groups, although T1OP patients were slightly younger and more often experienced falls or were victims of abuse. Compared to T1 activations, T1OP activations had a significantly higher mortality rate (21% vs. 7%, p<0.001). Repeat head imaging was more common in the T1OP(N) group compared to imaged children in the T1 group (20% vs. 37%, p=0.05). T1OP(N) patients more often went directly to the OR (45% vs. 33%, p=0.02) and did so in a significantly faster period of time (32min vs. 53min, p<0.001). CONCLUSIONS: Use of the T1OP activations appropriately triaged surgical patients, resulting in significantly faster transport times to the OR. LEVEL OF EVIDENCE: II, prognosis study.

Prior methamphetamine self-administration attenuates serotonergic deficits induced by subsequent high-dose methamphetamine administrations.

BACKGROUND: Pre-clinical studies indicate that high-dose, non-contingent methamphetamine (METH) administration both rapidly and persistently decreases serotonergic neuronal function. Despite research indicating the hippocampus plays an important role in METH abuse and is affected by METH use, effects of METH self-administration on hippocampal serotonergic neurons are not well understood, and were thus an important focus of the current study. Because humans often administer METH in a binge-like pattern, effects of prior METH self-administration on a subsequent "binge-like" METH treatment were also examined. METHODS: Rats were treated as described above, and sacrificed 1 or 8d after self-administration or 1h or 7d after the final binge METH or saline exposure. Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT) function were assessed. RESULTS: METH self-administration per se had no persistent effect on hippocampal 5HT content or SERT function. However, this treatment attenuated the persistent, but not acute, hippocampal serotonergic deficits caused by a subsequent repeated, high-dose, non-continent METH treatment administered 1 d the last self-administration session. No attenuation in persistent deficits were seen when the high-dose administration of METH occurred 15d after the last self-administration session. CONCLUSIONS: The present findings demonstrate that METH self-administration alters serotonergic neurons so as to engender "tolerance" to the persistent serotonergic deficits caused by a subsequent METH exposure. However, this "tolerance" does not persist. These data provide a foundation to investigate complex questions including how the response of serotonergic neurons to METH may contribute to contingent-related disorders such as dependence and relapse.