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Application for ESRA Abstract Prizes:Background and AimsIn spinal anesthesia, baricity determines intrathecal drug spread and block characteristics. Hyperbaric bupivacaine is widely used for lower limb arthroplasties. In our institution, it is routinely combined with preservative-free morphine to enhance postoperative analgesia. While this combination is common in clinical practice, its physicochemical effect on baricity has not been quantified. We aimed to evaluate the density - and hence baricity - of this custom-made intrathecal mixture.MethodsThe density of hyperbaric bupivacaine (Marcaine® Spinal 0.5% Heavy), morphine (100 µg/mL in saline), and their 2.2:1 mL and 2.4:1 mL (Marcaine®:morphine) mixtures were measured at room temperature using the Menarini Aution MAX AE-4030 system. Three samples of each solution were analyzed. Theoretical calculations were performed for validation.ResultsMean measured densities (standard deviation) in g/cm3 were: morphine 100 µg/mL: 1.004 (0.001); hyperbaric bupivacaine: 1.029 (0); mixture (2.2 + 1 mL): 1.021 (0.001); mixture (2.4 + 1 mL): 1.021 (confirmed in duplicate). Theoretically calculated densities for these mixtures were 1.0212 and 1.0216 g/cm3, respectively. Despite the dilution, the final mixture remains hyperbaric relative to CSF (~1.0003 g/cm3 at 37°C).ConclusionsThis is the first study to quantify the baricity of a commonly used morphine-bupivacaine spinal mixture. Although addition of the morphine solution lowers the density of hyperbaric bupivacaine, the mixture remains hyperbaric, supporting its continued clinical use with expected spread behavior. These findings reinforce the importance of physicochemical validation in custom-made intrathecal preparations.

Background and ObjectivesThe role of a fascia iliaca compartment block (FICB) for postoperative analgesia after total hip arthroplasty (THA) remains questionable. High-dose local anesthetics and a proximal injection site may be essential for successful analgesia. High-dose local anesthetics may pose a risk for local anesthetic systemic toxicity. We hypothesized that a high-dose longitudinal supra-inguinal FICB is safe and decreases postoperative morphine consumption after anterior approach THA.MethodsWe conducted a prospective, double blind, randomized controlled trial. Patients scheduled for THA were randomized to group FICB (longitudinal supra-inguinal FICB with 40-mL ropivacaine 0.5%) or group C (control, no block). Standard hypothesis tests (t test or Mann-Whitney U test, χ2 test) were performed to analyze baseline characteristics and outcome parameters. The primary end point of the study was total morphine (mg) consumption at 24 hours postoperatively. Serial total and free ropivacaine serum levels were determined in 10 patients.ResultsAfter obtaining ethical committee approval and written informed consent, 88 patients were included. Mean (SD) morphine consumption at 24 hours postoperatively was reduced in group FICB compared to group C: 10.25 (1.64) mg versus 19.0 (2.4) mg (P = 0.004). Using a mean dose of 2.6-mg/kg ropivacaine (range, 2–3.4 mg/kg), none of the patients had total or free ropivacaine levels above the maximum tolerated serum concentration.ConclusionsWe conclude that a high-dose longitudinal supra-inguinal FICB reduces postoperative morphine requirements after anterior approach THA.Clinical Trials Registry: EU Clinical Trials Register. www.clinicaltrialsregister.eu #2014-002122-12.

In the third step of the α -oxidation of 3-methyl-branched fatty acids such as phytanic acid, a 2-hydroxy-3-methylacyl-CoA is cleaved into formyl-CoA and a 2-methyl-branched fatty aldehyde. The cleavage enzyme was purified from the matrix protein fraction of rat liver peroxisomes and identified as a protein made up of four identical subunits of 63 kDa. Its activity proved to depend on Mg2+and thiamine pyrophosphate, a hitherto unrecognized cofactor of α -oxidation. Formyl-CoA and 2-methylpentadecanal were identified as reaction products when the purified enzyme was incubated with 2-hydroxy-3-methylhexadecanoyl-CoA as the substrate. Hence the enzyme catalyzes a carbon-carbon cleavage, and we propose calling it 2-hydroxyphytanoyl-CoA lyase. Sequences derived from tryptic peptides of the purified rat protein were used as queries to recover human expressed sequence tags from the databases. The composite cDNA sequence of the human lyase contained an ORF of 1,734 bases that encodes a polypeptide with a calculated molecular mass of 63,732 Da. Recombinant human protein, expressed in mammalian cells, exhibited lyase activity. The lyase displayed homology to a putative Caenorhabditis elegans protein that resembles bacterial oxalyl-CoA decarboxylases. Similarly to the decarboxylases, a thiamine pyrophosphate-binding consensus domain was present in the C-terminal part of the lyase. Although no peroxisome targeting signal, neither 1 nor 2, was apparent, transfection experiments with constructs encoding green fluorescent protein fused to the full-length lyase or its C-terminal pentapeptide indicated that the C terminus of the lyase represents a peroxisome targeting signal 1 variant.

The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence. In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause. GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy. Because of its euphoric effects, it became popular for recreational use under the street names: Liquid Ecstasy, Georgia Home Boy, and Liquid G. We describe the clinical case of a patient who suffered from severe neurological depression and HAGMA. Les causes de l’acidose métabolique à trou anionique élevé (AMTAE) sont bien présentées dans la documentation médicale. Toutefois, il arrive que des causes plus fréquentes d’AMTAE ne peuvent expliquer ce trouble. Dans les cas d’AMTAE et de dépression neurologique grave en l’absence d’autres facteurs étiologiques, les cliniciens devraient envisager la possibilité d’intoxication par le gammahydroxybutyrate (GHB). Le GHB est une substance endogène du système nerveux central des mammifères. Quant au GHB de synthèse, il était utilisé au début comme anesthésique, mais son emploi à des fins médicales n’est autorisé maintenant que dans un petit nombre d’indications telles que le traitement de la narcolepsie. Enfin, l’utilisation à des fins récréatives du GHB, communément appelé « ecstasy liquide », « Georgia Home boy » ou « Liquid G », a gagné beaucoup de terrain en raison de ses effets euphorisants. Sera exposé ici un cas clinique de dépression neurologique grave, accompagnée d’une acidose métabolique à trou anionique élevé.

JARID2 (Jumonji, AT Rich Interactive Domain 2) pathogenic variants cause a neurodevelopmental syndrome, that is characterized by developmental delay, cognitive impairment, hypotonia, autistic features, behavior abnormalities and dysmorphic facial features. JARID2 encodes a transcriptional repressor protein that regulates the activity of various histone methyltransferase complexes. However, the molecular etiology is not fully understood, and JARID2-neurodevelopmental syndrome may vary in its typical clinical phenotype. In addition, the detection of variants of uncertain significance (VUSs) often results in a delay of final diagnosis which could hamper the appropriate care. In this study we aim to detect a specific and sensitive DNA methylation signature for JARID2-neurodevelopmental syndrome. Peripheral blood DNA methylation profiles from 56 control subjects, 8 patients with (likely) pathogenic JARID2 variants and 3 patients with JARID2 VUSs were analyzed. DNA methylation analysis indicated a clear and robust separation between patients with (likely) pathogenic variants and controls. A binary model capable of classifying patients with the JARID2-neurodevelopmental syndrome was constructed on the basis of the identified episignature. Patients carrying VUSs clustered with the control group. We identified a distinct DNA methylation signature associated with JARID2-neurodevelopmental syndrome, establishing its utility as a biomarker for this syndrome and expanding the EpiSign diagnostic test.