Apparent local anesthetic systemic toxicity following activation of an epidural catheter for cesarean delivery: diagnosis and management of an uncommon obstetric anesthesia complication.

We present a 25-year-old, gravida 2, para 1 woman who developed apparent local anesthetic systemic toxicity (LAST) following activation of an epidural catheter for an urgent cesarean delivery. The patient had a height of 150 cm, weight of 92 kg, body mass index of 41 kg/m2, and calculated ideal body weight of 40 kg. A combined spinal epidural anesthetic was placed and the spinal component did not provide anesthesia to clamping of the abdomen. Subsequently, 300 mg of lidocaine was administered through the epidural catheter in three 5 mL doses over 8 minutes and surgery commenced. Approximately 30 minutes following the final 5 mL dose of epidural lidocaine, the patient had progressive loss of consciousness and was difficult to arouse. A presumptive diagnosis of LAST was made, and 60 mL of 20% intravenous lipid emulsion was administered. The patient's mental status improved to baseline within 5 minutes of lipid emulsion administration, and she made a complete recovery. Anesthesiologists should consider using ideal body weight when calculating the maximum dosage of local anesthetics, and LAST should be part of the differential diagnosis when patients have altered mental status in the setting of local anesthetic administration that exceeds recommended dosages.

Persistent disparities in insulin pump uptake despite a universal pump programme for type 1 diabetes in Ontario, Canada.

AIM: To evaluate associations between social disadvantage and insulin pump use among adults with type 1 diabetes (T1D) in the context of a universal publicly funded insulin pump programme in Ontario, Canada, and to ascertain whether social disparities in insulin pump programme enrolment have decreased over time. METHODS: Population-based cross-sectional studies were conducted using administrative healthcare data in Ontario, Canada. First, among adults aged older than 18 years diagnosed with T1D before 31 March 2021, logistic regression was used to assess the association between neighbourhood social disadvantage (Ontario marginalization index quintiles) and insulin pump use. Second, among all paediatric and adult applicants to the insulin pump programme from 1 September 2006 to 31 March 2022, ordinal logistic regression was used to evaluate associations between year of insulin pump initiation and social disadvantage. RESULTS: Among 27 453 adults with T1D, 60% used insulin pumps. Greater social disadvantage was associated with lower odds of insulin pump use (adjusted odds ratio [OR] 0.44 [95% confidence interval {CI} 0.39-0.48] for greatest vs. lowest social disadvantage quintile). Among 21 002 paediatric and adult applicants to the insulin pump programme, social disparities in pump use decreased in the first 3 years of the programme, plateaued until 2020, then increased from 2020 to 2022, with no change in the odds of being in a higher social deprivation quintile for 2022 relative to 2007 (OR 1.09 [95% CI 0.83-1.44]). CONCLUSIONS: Despite a universal pump programme for individuals with T1D, disparities by social disadvantage persist. Residual financial and non-financial barriers must be addressed to promote equitable insulin pump uptake.

Renalase Levels are Decreased in Maternal Blood and Placental Tissues in Pregnancies Associated with Preterm Preeclampsia.

Preeclampsia (PEC) is a complication of pregnancy associated with hypertension and the risk of eclampsia. The pathophysiology of PEC is unknown and identifying factors associated with PEC during pregnancy is crucial for placental, fetal, and maternal health. Renalase (RNLS) is an anti-inflammatory secretory flavoprotein associated with hypertension. Recent data demonstrated a correlation between maternal serum RNLS and PEC, and work from our group identified RNLS expression in the placenta. However, it remains unknown whether RNLS levels in placenta are altered by preeclampsia. Additionally, it is unclear if there is a differential effect of preterm and term PEC on RNLS. We demonstrate that serum RNLS was reduced in preterm cases of PEC. Similarly, placental RNLS was diminished in the chorion of preterm cases of PEC. However, a reduction of RNLS in the decidua was observed with all cases of PEC, while the levels of RNLS within the placental villi were similar in all cases. Overall, we demonstrate that RNLS correlates with PEC both systemically in maternal serum and locally within the placenta, with variable effects on the different layers of the placenta and more pronounced in preterm cases.

The use of prescription medications and non-prescription medications during lactation in a prospective Canadian cohort study.

BACKGROUND: A lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation. METHODS: Data were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use. RESULTS: A total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum. CONCLUSIONS: In Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation.

Cardiac migration of an implanted hepatic fiducial marker used for stereotactic body radiation therapy - A case report.

ABSTRACT: Stereotactic body radiation therapy (SBRT) has been increasingly used to treat liver malignancies because large doses of radiation can be delivered precisely to the target with a rapid dose falloff. Real-time tracking of implanted fiducial markers (FMs), combined with respiratory gating, further improves the accuracy of treatment delivery and reduces the dose to critical structures. There have been reports of migration of the FMs after implantation for SBRT. Calypso beacons, which use the electromagnetic wave reflections for the image guidance, have recently been used for image-guided liver SBRT. In the literature, there are no reports on the migration of Calypso beacons to the heart after implantation in the liver. In this report, we detail the first case of such migration. Respiratory-gated SBRT guided by the Calypso system was planned for our patient, who developed liver metastases in segments 6 and 5/4B shortly after the completion of radical chemoradiotherapy for anal squamous cell carcinoma. One of the three Calypso beacons inserted in the liver under computed tomography (CT) guidance was found to have migrated to the right ventricle, as seen in CT simulation images. SBRT was delivered with respiratory gating using the remaining two beacons. A fluoroscopic imaging performed during treatment confirmed the migrated marker to the right ventricle. Patient denied any cardiac symptoms and SBRT were delivered uneventfully. Ten months later, the patient died of disease progression.

Migration of Calypso beacon transponders for hepatic stereotactic body radiotherapy: a report of two cases.

Background: The Calypso 4-dimensional Localization System allows the delivery of high-dose of radiation to a target guided by the implanted transponders. Calypso beacons are used for prostate and liver tumors treated with stereotactic body radiation therapy (SBRT). Several risks associated with this procedure have been previously observed. Here, we report on two cases where Calypso soft tissue transponders migrated to the lung shortly after implantation in liver. Case Description: Two male patients with hepatocellular carcinoma (HCC) underwent insertion of Calypso beacons in liver under image-guidance in preparation for SBRT. Post-procedure images confirmed the presence of the transponders within the liver. However, few days after implant, further imaging revealed a missing marker, in each patient, that had migrated to the right lung. Patients were asymptomatic and SBRT was delivered uneventfully. Conclusions: This is the first report of migration of Calypso beacons from liver to lung. In order to reduce the risk of migration, a Doppler ultrasound (US) prior to insertion could be performed to ensure that the transponders are at a safe distance from blood vessels. Anchored Calypso beacons, currently approved for insertion in the lung, could be tested as a suitable alternative to soft tissue beacons with a lower risk of migration.

PKC epsilon as a neonatal target to correct FXS-linked AMPA receptor translocation in the hippocampus, boost PVN oxytocin expression, and normalize adult behavior in Fmr1 knockout mice.

Fragile X Syndrome (FXS) is an inherited developmental disorder caused by the non-expression of the Fmr1 gene. FXS is associated with abnormal social and anxiety behavior that is more prominent among males. Given that oxytocin (OXT) regulates both social and anxiety behavior, we studied the effect of FXS in the hypothalamic paraventricular nucleus (PVN), the major central source of OXT. We observed a significant suppression of protein kinase C epsilon (PKCε) (34%) in the ventral hippocampal CA1 region of postnatal day-18 (P18) male Fmr1 knockout (KO) mice, which displayed social behavior deficits and hyper-anxiety in adulthood. These mice also displayed a 39% increase in cell surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) at P18 (measured by the surface level of the AMPAR subunit GluR2), thereby indicating excitation of the CA1 neurons. It is known that neuronal activation at CA1 is linked to an inhibition of the PVN neurons. As expected, these mice also displayed a 25% suppression of oxytocin+ (OXT+) cells in the PVN at P20. Stimulating PKCε during postnatal days 6-,14 (P6-14) mice using a selective activator, dicyclopropyl-linoleic acid (DCP-LA), corrected AMPAR externalization in CA1 and suppression of OXT+ cell number in PVN in a PKCε dependent manner. Most notably, neonatal DCP-LA treatment rescued social behavior deficits and hyper-anxiety, displayed by adult (≥P60) male but not female KO mice. Thus, neonatal stimulation of PKCε could be a strategy to correct endophenotypic anomalies during brain development and aberrant adult behavior of the FXS males to the wild-type levels.