Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice.

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain injury and genetic risk in the induction of FTD/ALS pathology we combined a mild repetitive traumatic brain injury paradigm with an established bacterial artificial chromosome transgenic C9orf72 (C9BAC) mouse model without an overt motor phenotype or neurodegeneration. We assessed 8-10 week-old littermate C9BACtg/tg (n = 21), C9BACtg/- (n = 20) and non-transgenic (n = 21) mice of both sexes for the presence of behavioural deficits and cerebral histopathology at 12 months after repetitive TBI. Repetitive TBI did not affect body weight gain, general neurological deficit severity, nor survival over the 12-month observation period and there was no difference in rotarod performance, object recognition, social interaction and acoustic characteristics of ultrasonic vocalizations of C9BAC mice subjected to repetitive TBI versus sham injury. However, we found that repetitive TBI increased the time to the return of the righting reflex, reduced grip force, altered sociability behaviours and attenuated ultrasonic call emissions during social interactions in C9BAC mice. Strikingly, we found that repetitive TBI caused widespread microglial activation and reduced neuronal density that was associated with loss of histological markers of axonal and synaptic integrity as well as profound neuronal transactive response DNA binding protein 43 kDa mislocalization in the cerebral cortex of C9BAC mice at 12 months; this was not observed in non-transgenic repetitive TBI and C9BAC sham mice. Our data indicate that repetitive TBI can be an environmental risk factor that is sufficient to trigger FTD/ALS-associated neuropathology and behavioural deficits, but not paralysis, in mice carrying a C9orf72 hexanucleotide repeat expansion.

Risk of Postdural Puncture Headache in Adolescents and Adults.

BACKGROUND: Spinal anesthesia is known to have numerous benefits, including reductions in nausea and opioid consumption; however, postdural puncture headache (PDPH) remains a significant risk associated with this technique. The literature specifically examining this complication in adolescents is scarce. Our primary objective was therefore (1) to estimate the incidence of PDPH with a 27G pencil-point needle in patients between the ages of 12 and 19 undergoing ambulatory lower extremity procedures and (2) to compare it to the incidence in adults aged 20-45 years. METHODS: After institutional review board (IRB) approval, patients aged 12-45 years undergoing ambulatory lower extremity surgery were approached. Patients undergoing the procedure under combined spinal-epidural (CSE) or spinal anesthesia with a 27G pencil-point needle were eligible for enrollment. Patients were consented before surgery and received a survey via e-mail on postoperative day (POD) 4 inquiring about the presence of a headache. Each headache was described by the participant and assessed for severity, time of onset, duration, location, and whether it was of a postural nature. All patients reporting a postural headache were contacted by a physician author to confirm a diagnosis of PDPH using the International Headache Society diagnostic criteria. RESULTS: A total of 656 patients were included in the analysis. Overall, 3.4% of patients developed PDPH. The percentage developing PDPH was 4.9% (3.0-7.8) among those aged 12-19 years and 1.8% (0.8-3.9) in the 20- to 45-year-old group. After adjusting for covariates, the age group between 12 and 19 years was associated with an almost 3-fold increase in the odds (2.8 [95% confidence interval {CI}, 1.1-7.3]) for the development of PDPH compared to that in the 20-45 age group. One patient in the adult group required an epidural blood patch. CONCLUSIONS: The overall incidence for the development of PDPH in ambulatory patients <45 years of age is low. However, the odds for developing PDPH is significantly higher in teenagers compared to those aged 20-45 years. This increase was not associated with an increase in the need for an epidural blood patch. Providers may incorporate these data in their consent process and have a higher index of suspicion for PDPH in teenagers who report headaches after neuraxial anesthesia.

Teaching a Point-of-Care Ultrasound Curriculum to Anesthesiology Trainees With Traditional Didactic Lectures or an Online E-Learning Platform: A Pilot Study.

BACKGROUND: Point-of-care ultrasonography (PoCUS) provides real-time, dynamic clinical evidence for providers to make potentially lifesaving medical decisions; however, these tools cannot be used effectively without appropriate training. Although there is always the option of traditional didactic methods, there has been a recent trend toward a "reverse classroom" web-based model using online e-learning modules. Our objective was to collect pilot data that would justify a future randomized controlled trial, comparing traditional didactics to an e-learning PoCUS curriculum for lung ultrasonography (LUS) and the focused assessment with sonography in trauma (FAST) exam. METHODS: Anesthesiology interns, residents (CA 1-3), and fellow trainees enrolled in a LUS and FAST exam course and were randomized to receive didactic lectures or e-learning. Trainees completed knowledge pre- and posttests. Surveys were administered to gauge learning satisfaction. All trainees completed a hands-on-training (HOT) workshop. Image acquisition was assessed through practical tests before HOT, immediately after HOT, and 5 months later. RESULTS: Eighteen trainees completed the study. There was no evidence of a difference in change in LUS knowledge test score from baseline to posttest between the e-learning and didactic groups (difference in median percentage point change [95 % CI]: 6.6 [-10.0, 23.2]; P = .411). There was no evidence of a difference in LUS knowledge posttest scores (difference in median percentage points [95% CI]: -0.9 [-4.8, 3.0]; P = .629), FAST knowledge posttest score (0 [incalculable]; P = .999), or post-HOT practical test score (-4.2 [-24.6, 16.3]; P = .672) between groups. There was no evidence of a difference in degree of satisfaction with learning experience between groups (odds ratios [95% CI]: 1.75 [0.31, 9.94]; P = .528). CONCLUSIONS: There was no evidence of a difference between the e-learning and traditional didactic groups in learning or satisfaction outcomes. These results justify establishing an adequately powered, randomized controlled trial assessing the noninferiority of e-learning to traditional didactics for teaching LUS and FAST.

Readiness for Discharge After Foot and Ankle Surgery Using Peripheral Nerve Blocks: A Randomized Controlled Trial Comparing Spinal and General Anesthesia as Supplements to Nerve Blocks.

BACKGROUND: Neuraxial anesthesia is often viewed as superior to general anesthesia but may delay discharge. Comparisons do not typically use multimodal analgesics and nerve blockade. Combining nerve blockade with general anesthesia may reduce pain, opioid consumption, and nausea. We hypothesized that general anesthesia (with nerve blocks) would lead to earlier readiness for discharge, compared to spinal anesthesia (with nerve blocks). METHODS: All patients underwent ambulatory foot and ankle surgery, with a predicted case duration of 1-3 hours. All patients received popliteal and adductor canal nerve blocks using bupivacaine and dexamethasone. No intraoperative opioids were administered. All patients received ondansetron, dexamethasone, ketamine, and ketorolac. Patients, data collectors, and the data analyst were not informed of group assignment. Patients were randomized to spinal or general anesthesia with concealed allocation. Spinal anesthesia was performed with mepivacaine and accompanied with propofol sedation. After general anesthesia was induced with propofol, a laryngeal mask airway was inserted, followed by sevoflurane and propofol. Time until ready for discharge, the primary outcome, was compared between groups after adjusting for age and surgery time using multivariable unconditional quantile regression. Secondary outcomes compared at multiple timepoints were adjusted for multiple comparisons using the Holm-Bonferroni step-down procedure. RESULTS: General anesthesia patients were ready for discharge at a median of 39 minutes earlier (95% confidence interval, 2-75; P = .038) versus spinal anesthesia patients. Patients in both groups met readiness criteria for discharge substantially before actual discharge. Pain scores at rest were higher among general anesthesia patients 1 hour after leaving the operating room (adjusted difference in means, 2.1 [95% confidence interval, 1.0-3.2]; P < .001). Other secondary outcomes (including opioid use, opioid side effects, nausea, headache, sore throat, and back pain) were not different. CONCLUSIONS: General anesthesia was associated with earlier readiness for discharge, but the difference may not be clinically significant and did not lead to earlier actual discharge. Most secondary outcomes were not different between groups. The choice of spinal or general anesthesia as an adjunct to peripheral nerve blockade can reflect patient, clinician, and institutional preferences.

Clinical Indicators of the Need for Telemetry Postoperative Monitoring in Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee Arthroplasty.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with increased complication rates postoperatively. Current literature does not provide adequate guidance on management of these patients. This study used the STOP-Bang questionnaire to diagnose patients with possible obstructive sleep apnea (score ≥3). We hypothesized that a STOP-Bang score of 3 or greater would significantly correlate with the number of oxygen desaturation episodes during the first 48 hours after total knee arthroscopy. METHODS: The STOP-Bang questionnaire was administered to 110 patients preoperatively. All patients underwent spinal-epidural anesthesia with a saphenous nerve block and sedation and were connected to the Nellcor OxiMax N-600x pulse oximeter for 48 hours postoperatively. RESULTS: Final analysis included 98 patients. There was no significant difference in the total number of desaturation events between STOP-Bang groups (score <3 vs ≥3 and score <5 vs ≥5). The total number of desaturation events on postoperative day 1 was greater than that on day 0 (32.8 ± 42.7 vs 4.1 ± 10.0, P < 0.0001). The total number of desaturation events correlated with length of hospital stay (r = 0.329, P = 0.0001). Patients with a preoperative serum CO2 of 30 mmol/L or greater had significantly longer episodes of desaturation on postoperative day 0 compared with CO2 of less than 30 mmol/L (233.7 ± 410.1 vs 82.0 ± 126.2 seconds, P = 0.044). CONCLUSIONS: A high preoperative value of CO2 should be a warning for possible prolonged episodes of desaturation postoperatively. An attempt to limit postoperative desaturation events should be made to minimize length of stay.

The timing of embryonic exposure to elevated temperature alters stress endocrinology in domestic chickens (Gallus domesticus).

Patterns of glucocorticoid (GC) release in response to stimuli vary both among individuals and within individuals across their lifetime. While much work has focused on how the prenatal steroid environment can affect GC release, relatively little is known about how environmental parameters, such as incubation temperature affect GCs. We tested the hypothesis that variation and timing of elevated incubation temperature within the thermoneutral zone can alter the pattern of GC release. We incubated domestic chicken eggs (Gallus domesticus) at the optimal incubation temperature (37.5 °C) or at a slightly higher temperature (+1.1 °C) either early, late, or throughout incubation. At three weeks post-hatch, all birds were (i) exposed to a capture-restraint stress to measure stress-induced GC release (naïve). Three days following the naïve stressor, birds were (ii) exposed to a heat challenge, which was followed the next day by a second capture-restraint stress (post-heat challenge). Regardless of treatment, birds had similar patterns of GC release following the naïve stress series. However, during the post-heat challenge stress series, birds incubated at optimal temperatures increased their peak GC release. In contrast, birds exposed to slightly elevated temperatures for any period of development failed to increase peak GC release, and their specific response varied with timing of exposure to the elevated incubation temperature. Our results demonstrate that subtle variation in the embryonic environment, such as elevated incubation temperature within the thermoneutral zone, can impact the pattern of GC release of offspring. Further work is needed to understand the mechanisms underlying these changes and the relationship between fitness and environmentally-altered phenotypes.