Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial.

IMPORTANCE: There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE: To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS: Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES: Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS: There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE: In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313716.

Maternal care alterations induced by repeated ethanol leads to heightened consumption of the drug and motor impairment during adolescence: a dose-response analysis.

Maternal ethanol exposure during lactation induces behavioral alterations in offspring, including disruptions in motor skills and heightened ethanol ingestion during adolescence. These behavioral outcomes appear to partially depend on ethanol-induced disruptions in maternal care. The present study assessed motor skills and ethanol intake in adolescent rats raised by dams that had been repeatedly given ethanol during lactation. Female rats (postpartum days [PDs] 3-13) were administered ethanol (0.5, 1.5, or 2.5 g/kg) or vehicle every other day and allowed to freely interact with their pups. During adolescence, the offspring were evaluated for motor coordination (accelerating rotarod test) and oral ethanol self administration. The lowest maternal ethanol dose (0.5 g/kg) mildly affected motor performance, whereas the higher doses (1.5 and 2.5 g/kg) resulted in motor coordination impairment and greater ethanol intake. Maternal care behavior was affected by ethanol in a dose-dependent fashion. These results indicate that early experience with ethanol during lactation, even when the drug dosage is kept relatively low, leads to long-term consequences in offspring. Dose-response effects on maternal care behavior (i.e., nest building, crouching) may underlie disruptions in motor development and greater ethanol intake resulting from these early ethanol experiences.

Ethanol-mediated operant learning in the infant rat leads to increased ethanol intake during adolescence.

Recent studies indicate that the infant rat has high affinity for ethanol ingestion and marked sensitivity to the drug's reinforcing effects [Spear, N.E., Molina, J.C. Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review. Alcohol Clin Exp Res 2005; 29: 909-29.]. A novel operant technique was developed to analyze reinforcing effects of ethanol delivery during the third postnatal week. The impact of this ethanol-reinforcement experience upon subsequent ethanol consumption during adolescence (postnatal weeks 5-6) was also examined. In Experiment 1, pups (postnatal days 14-17) were given an explicit contingency between nose-poking behavior and intraoral delivery of either water or 3.75% v/v ethanol (paired groups). Yoked controls (pups receiving either reinforcer independently of their behavior) were also included. Paired subjects reinforced with ethanol exhibited rapid and robust operant conditioning leading to blood ethanol concentrations in the 25-48 mg% range. In Experiment 2, a higher ethanol concentration (7.5% v/v) provided significant reinforcement. During adolescence, animals originally reinforced with 3.75% v/v ethanol exhibited greater ingestion of ethanol than control animals without prior ethanol reinforcement. These results indicate that, without extensive initiation to ethanol, infant rats rapidly learn to gain access to ethanol and that this experience has a significant impact upon later ethanol intake patterns.

Infantile sensitivity to ethanol's motivational effects: Ethanol reinforcement during the third postnatal week.

BACKGROUND: Although tests specific to newborn rats have frequently verified their susceptibility to the reinforcing properties of ethanol, demonstration of comparable reinforcing effects in older infants has been elusive. Using a second-order conditioning procedure, the present study assessed in preweanling rats whether pairing with early postabsorptive effects of ethanol would render intraorally delivered gustatory stimuli capable of positive reinforcement for association with a salient texture. Direct reinforcing effects of ethanol were also evaluated through intake tests of gustatory stimuli previously paired with the drug. Blood ethanol levels (BELs) were determined for each of the ethanol doses used. METHODS: Pups (14 days old) were stimulated with intraoral infusion of sucrose (10% v/v), water, or quinine (0.0045% w/v) 5 minutes after being intragastrically (i.g.) administered 0.00, 0.25, 0.50, or 2.00 g/kg ethanol (Experiments 1 and 2). These stimuli were then briefly presented while pups experienced a rough texture (sandpaper). Rats were subsequently evaluated in a 2-way texture location test (sandpaper vs smooth surface). In Experiment 3, sucrose, water, or quinine was paired with early postabsorptive effects of ethanol (0.00, 0.50, or 2.0 g/kg). Consumption of these stimuli was later assessed. Motor activity patterns during the intake test were also evaluated. In Experiment 4, BELs corresponding to 0.25, 0.50, or 2.0 g/kg ethanol were determined 5 and 20 minutes after i.g. administration (time periods were in accord with the onset and offset of intraoral stimulation used in the previous experiments). RESULTS: Intraoral infusion of sucrose, water, or quinine, while under a state of sobriety and paired with sandpaper, resulted in roughly 50% preference for this texture. Sandpaper preferences were significantly elevated in pups that had experienced sucrose or water in a nonsober state-while under the effects of ethanol (Experiments 1 and 2). This indicated reinforcing effects of the ethanol intoxication. Pairing ethanol intoxication directly with consumption of sucrose, water, or quinine did not affect their later consumption. Yet, there were clear indications that this pairing resulted in conditioned behavioral activity patterns. Blood ethanol levels corresponding to the ethanol doses used here ranged between 10 and 150 mg%. CONCLUSIONS: Infants appear sensitive to pharmacological reinforcing properties of low and relatively high ethanol doses. This sensitivity was revealed indirectly, by pairing gustatory stimuli with ethanol intoxication and then allowing these stimuli to act as second-order reinforcement for a quite different (tactile) stimulus. Behavioral activation elicited by the gustatory stimuli previously paired with a state of intoxication seems to compete with the expression of ethanol's motivational properties as assessed through intake tests.

Efectos de la exposición temprana al etanol sobre subsiguientes aprendizajes mediados por los atributos incondicionales de la droga / Effects of early exposure to ethanol on subsequent learning mediated by the unconditional attributes of the drug

Se investigaron respuestas condicionadas táctiles y gustativas promovidas por el etanol durante la temprana ontogenia de la rata y se observaron los efectos de la preexposición al psicotrópico sobre estos aprendizajes; En los días posnatates (DPP) 10 al 13 (fase de preexposición) las crías fueron administradas diariamente con 0 o 2,5 g/kg de etanol, en tanto que en los DPP 14 y 15 (fase de condicionamiento) los animales recibieron 0, 0,5 o 2,5 g/kg de etanol, experimentando la exposición a una textura (lija) y a un gusto (sacarina) durante los períodos posadministración 5-15 min y 25-35 min, respectivamente. Asimismo, se registraron los niveles de alcohol en sangre (NAS) inducidos por las dosis etílicas bajo análisis. En el DPP 16 se observó, independientemente de la preexposición a la droga, una disminución del consumo de sacarina en los sujetos que habían recibido etanol durante el condicionamiento. Una prueba de preferencia táctil no indicó preferencias o aversiones hacia la lija. Sin embargo, los sujetos condicionados con la dosis de2,5 g/kg (NAS máximos: 204 mg por ciento) y sin preexposición al psicotrópico exhibieron una significativa hipolocomoción durante la prueba, fenómeno que se vio inhibido en función de la preexposición a la droga. En conclusión, se observó una alta sensibilidad a los efectos aversivos del etanol en las ratas lactantes, aun empleando dosis bajas (03 g/kg; MAS máximos: 42 mg por ciento) y tras una fase de preexposición a la droga. Sin embargo, la experiencia etílica previa afecta respuestas locomotoras aprendidas mediadas por una dosis etílica relativamente elevada

Acute ethanol counteracts the acquisition of aversive olfactory learning in infant rats.

Rodents are particularly prone to acquire associative memories during early stages of life. Yet, very little is known about how ethanol interacts with simultaneous associative learning acquired during postabsorptive periods. We have recently observed that preweanling rats avoid lemon odor previously paired with the intraoral infusion of a sapid sweet solution, a result likely to be caused by aversive consequences inherent to this procedure. Two experiments were conducted to analyze the effects of acute ethanol upon the acquisition of this avoidance response. Fourteen-day-old Wistar rats were intragastrically administered with ethanol (0.0, 0.25, 0.5, or 1.25 g/kg) and then exposed for 5 min to a lemon-scented chamber while being intraorally infused with sucrose (12% vol/vol). Four of such pairings were conducted immediately after ethanol administration. Control pups experienced these stimuli in an unrelated fashion. On postnatal day 15 animals were tested in a 5-min, two-way odor-preference test. Pups administered with vehicle during the acquisition phase exhibited a strong aversion to the lemon odor relative to control subjects. This avoidance response was reduced in pups that received 0.5 and 1.25 g/kg doses, whereas it completely vanished in those that received 0.25 g/kg dose. In a second experiment it was observed that, 10 min after the administration, blood ethanol concentrations attained with the 0.25, 0.5, and 1.25 g/kg doses were 11, 39, and 83 mg%, respectively. These data indicate that a very low dose of ethanol is able to counteract early aversive associative learning, a result likely to be mediated by anxiolytic properties of ethanol.

Nursing from an ethanol-intoxicated dam induces short- and long-term disruptions in motor performance and enhances later self-administration of the drug.

RATIONALE: During interactions with an ethanol-intoxicated dam, preweanling rats encode ethanol-related chemosensory information. These experiences have been observed to enhance subsequent recognition of ethanol's chemosensory properties and to modulate learning about ethanol. OBJECTIVE: The present study tested the effects of ethanol-related nursing experiences on motor function in later infancy and adolescence and on ethanol intake during adolescence. METHODS: Wistar-derived rats were reared by dams intragastrically administered with ethanol (2.5 g/kg) or with water during postnatal days (PDs) 3, 5, 7, 9, 11, and 13. Later in infancy or in adolescence, these rats were tested on a motor coordination task (Accelerod) while either sober or acutely intoxicated with ethanol (1 g/kg). During adolescence, animals had simultaneous access to varying ethanol concentrations (3, 4, 5, or 6% v/v) and water. RESULTS: Both infants and adolescents that had been reared by ethanol-intoxicated dams exhibited dramatic behavioral impairments in the Accelerod task when compared with the offspring of water control dams. Ethanol intoxication disrupted motor performance in both age groups, but this effect was independent of prior maternal treatment. When tested for voluntary ethanol intake as adolescents, those with prior nursing experiences with an intoxicated dam ingested more ethanol than adolescents reared by sober dams. CONCLUSIONS: Early experiences with alcohol comprising interactions with an alcohol-intoxicated dam result in motor impairment and enhanced ethanol intake later in life.