Exploring pregnant individuals' counseling needs regarding urgent imaging to rule out pulmonary embolism.

Background: Computed tomography pulmonary angiogram and lung scintigraphy with ventilation/perfusion scan are needed to diagnose pulmonary embolism (PE) in pregnancy. Their associated ionizing radiation doses are considered safe in pregnancy. A standardized patient information tool may improve patient counseling and reduce testing hesitancy. Objectives: In this context, we sought to address 1) what patients want to know before undergoing these tests and 2) how they want the information to be provided to them. Methods: We used a qualitative descriptive methodology. We recruited pregnant participants at the McGill University Health Center in Montreal, Canada. Structured interviews explored information needs about PE and diagnostic imaging for PE. The interview transcripts' themes were analyzed with a hybrid deductive and inductive approach. Results: Of 21 individuals approached, 20 consented to participate. Four had been previously investigated for PE. Participants requested information about the risks associated with PE and radiation and their effects on maternal and fetal health. They preferred for radiation doses to be presented in comparison with known radiation thresholds for fetal harm. They suggested that a written tool should be developed using an accessible language. Participants also indicated that the tool would be integrated into their decision-making process, emphasizing a lower risk tolerance for their fetus than for themselves. Conclusion: This single-center group of pregnant patients wished to be informed about the risks of PE and radiation associated with imaging. A written tool could help put information into context and facilitate decision making. These new insights may be used to inform counseling.

Factor XI Inhibitors: Potential Role in End-Stage Kidney Disease.

Patients with end-stage kidney disease (ESKD) experience a high thrombotic risk but are also at increased risk of bleeding. There is an unmet need for safer antithrombotic therapy in patients with ESKD on hemodialysis. Factor XI (FXI) represents an attractive therapeutic target for anticoagulation because of the potential to mitigate the bleeding risks associated with currently approved anticoagulants, especially in patients at high risk of bleeding. FXI inhibition is also an attractive option in settings where coagulation is activated by exposure of the blood to artificial surfaces, including the extracorporeal circuit during hemodialysis. Therapies targeting FXI that are in the most advanced stages of clinical development include antisense oligonucleotides, monoclonal antibodies, and synthetic small molecules, which serve either to lower FXI levels or block its physiological effects. This review article presents the most recent pharmacological data with FXI inhibitors, briefly describes phase 2 and 3 clinical trials with these agents, and critically examines the potential future use of FXI inhibitors for extracorporeal circuit anticoagulation in patients with ESKD. In addition, laboratory monitoring and reversal of FXI inhibitors are briefly discussed.

A Simple Admission Order-set Improves Adherence to Canadian Guidelines for Hospitalized Patients With Severe Ulcerative Colitis.

Background: Individuals hospitalized with severe ulcerative colitis represent a complex group of patients. Variation exists in the quality of care of admitted patients with inflammatory bowel disease. We hypothesized that implementation of a standardized admission order set could result in improved adherence to current best practice guidelines (Toronto Consensus Statements) for the management of this patient population. Methods: A retrospective cohort study of patients admitted with severe ulcerative colitis to a Montreal tertiary center was conducted. Two cohorts were defined based on pre- and post-implementation of a standardized order set. Adherence to 11 quality indicators was assessed before and after implementation of the intervention. These included: Clostridioides difficile and stool cultures testing, ordering an abdominal X-ray and CRP, organizing a flexible sigmoidoscopy, documenting latent tuberculosis, initiating thromboprophylaxis, use of intravenous steroids, prescribing infliximab if refractory to steroids, limiting narcotics, and surgical consultation if refractory to medical therapy. Results: Adherence to 6 of the 11 quality indicators was improved in the post-intervention cohort. Significant increases were noted in adherence to C difficile testing (75.5% versus 91.9%, P < 0.05), CRP testing (71.4% versus 94.6%, P < 0.01), testing for latent tuberculosis (38.1% versus 84.6%, P < 0.01), thromboprophylaxis (28.6% versus 94.6%, P < 0.01), adequate corticosteroids prescription (72.9% versus 94.6%, P < 0.01), and limitation of narcotics prescribed (68.8% versus 38.9%, P < 0.01). Conclusions: Implementation of a standardized order set, focused on pre-defined quality indicators for hospitalized patients with severe UC, was associated with meaningful improvements to most quality indicators defined by the Toronto Consensus Statements.

Echocardiography findings in amniotic fluid embolism: a systematic review of the literature.

PURPOSE: Amniotic fluid embolism (AFE) is a leading cause of obstetrical cardiac arrest and maternal morbidity. The pathogenesis of hemodynamic collapse is thought to be from right ventricular (RV) failure; however, there is a paucity of data documenting echocardiography findings in this population. We undertook a systematic review of the literature to evaluate the echocardiography findings in patients with AFE. SOURCES: We retrieved all case reports and case series reporting AFE in Embase and MEDLINE from inception to 20 November 2021. Studies reporting AFE diagnosed by fulfilling at least one of three different proposed AFE criteria and echocardiography findings during hospitalization were included. Patient and echocardiographic data were retrieved, and univariate logistic regression analysis was performed for outcomes of interest. Bias was assessed using the Joanna Briggs Institute clinical appraisal tool for case series. PRINCIPAL FINDINGS: Eighty publications reporting on 84 patients were included in the final review. Fifty-five out of 82 patients with data (67%) showed RV dysfunction, including 11/82 (13%) with biventricular dysfunction; 14/82 (17%) had normal systolic function. No data on RV or left ventricular function were reported for two patients. The presence of RV dysfunction on echocardiography was associated with cardiac arrest (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.39 to 9.67; P = 0.009), and a composite risk of cardiac arrest, maternal death or use of extracorporeal membrane oxygenation (OR, 3.86; 95% CI, 1.43 to 10.4; P = 0.007). A low risk of bias was observed in 15/84 (18%) cases. CONCLUSIONS: Right ventricular dysfunction on echocardiography is a common finding in AFE and is associated with a high risk of cardiac arrest. The finding of RV dysfunction on echocardiography may help diagnose AFE and help triage the highest risk patients with AFE. STUDY REGISTRATION: PROSPERO (CRD42021271323); registered 1 September 2021.

RéSUMé: OBJECTIF: L'embolie amniotique (EA) est l'une des principales causes d'arrêt cardiaque obstétrical et de morbidité maternelle. Il est présumé que la pathogenèse du choc hémodynamique provient d'une défaillance ventriculaire droite (VD). Cependant, il y a peu de données documentant les constatations de l'examen échocardiographique dans cette population. Nous avons effectué une revue systématique des données probantes visant à évaluer l'utilité de l'échocardiographie chez les patientes atteintes d'embolie amniotique. SOURCES: Nous avons évalué tous les rapports de cas et séries de cas rapportant une EA dans les bases de données Embase et MEDLINE de leur création jusqu'au 20 novembre 2021. Les études rapportant une EA diagnostiquée en remplissant au moins l'un des trois critères d'EA proposés et les résultats échocardiographiques pendant l'hospitalisation ont été incluses. Les données sur les patientes et échocardiographiques ont été colligées, et une analyse de régression logistique univariée a été effectuée pour les issues cliniques d'intérêt. Le risque de biais a été évalué à l'aide de l'outil d'évaluation clinique de l'Institut Joanna Briggs pour les séries de cas. CONSTATATIONS PRINCIPALES: Quatre-vingts publications incluant 84 patientes ont été incluses dans la revue finale. Cinquante-cinq des 82 patientes présentant des données (67 %) avaient une dysfonction du VD incluant 11/82 (13 %) avec une dysfonction biventriculaire. Quatorze patientes sur 82 (17 %) avaient une fonction systolique normale. Aucune donnée sur la fonction du ventricule droit ou gauche n'a été rapportée pour deux patientes. La présence d'une dysfonction du VD à l'échocardiographie était associée à un arrêt cardiaque (rapport de cotes [RC], 3,66; intervalle de confiance à 95 % [IC], 1,39 à 9,67; P = 0,009), et à un risque composite d'arrêt cardiaque, de décès maternel ou d'utilisation de l'oxygénation par membrane extracorporelle (ECMO) (RC, 3,86; IC 95 %, 1,43 à 10,4; P = 0,007). Un faible risque de biais a été observé dans 15/84 (18 %) des cas. CONCLUSION: La dysfonction ventriculaire droite à l'échocardiographie est une constatation courante dans l'embolie amniotique et est associée à un risque élevé d'arrêt cardiaque. La découverte d'une dysfonction du VD à l'échocardiographie peut aider à diagnostiquer l'embolie amniotique et à identifier les patientes atteintes d'embolie amniotique les plus à risque. ENREGISTREMENT DE L'éTUD: PROSPERO (CRD42021271323); enregistrée le 1er septembre 2021.

Hemophagocytic lymphohistiocytosis in pregnancy evolving towards fulminant hepatitis.

Background: Hemophagocytic lymphohistiocytosis is a rare disorder, especially in pregnancy, characterized by excessive immune activation leading to hemophagocytic activity. Case Report: A 34-year-old woman presented at 31 weeks' gestation with fever, cytopenias, hyperferritinemia and fulminant hepatitis. Bone marrow biopsy was non-contributory, and no trigger was identified. Liver biopsy confirmed the diagnosis of hemophagocytic lymphohistiocytosis, and she received dexamethasone and etoposide, which was changed to anakinra to allow breastfeeding. Prompt diagnosis and treatment of hemophagocytic lymphohistiocytosis is crucial to the survival of pregnant women, but no consensus exists regarding the most appropriate therapy during pregnancy. Conclusion: Hemophagocytic lymphohistiocytosis is life-threatening and associated with significant morbidity and mortality. Important treatment considerations in pregnancy include maternal health, fetal prematurity and treatment toxicity. Anakinra has been successfully used in pregnancy and provides a promising alternative.

Bleeding in women with venous thromboembolism during pregnancy: A systematic review of the literature.

Objectives: Venous thromboembolism (VTE) represents an important cause of maternal morbidity and mortality. Estimates of bleeding associated with therapeutic-dose anticoagulation are variable. We describe the frequency of bleeding in pregnant women receiving therapeutic anticoagulation for VTE by means of a systematic review of the literature. Data Sources: Medical Literature Analysis and Retrieval System, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched. Databases were searched from inception to February 27, 2022. There was no language or geographic location restriction. Methods of Study Selection: The search yielded 2773 articles with 2212 unique citations. Studies were included if they described pregnant women treated for an acute VTE with therapeutic-dose anticoagulation and a defined bleeding outcome was reported. Tabulation Integration and Results: Five studies met inclusion criteria. Included studies were judged to have a serious to critical risk of bias using the Risk of Bias in Nonrandomized Studies of Intervention tool. The rate of bleeding, as defined by respective studies, ranged between 2.9% and 30.0%. Two studies included control groups, one of which found no significant difference in the risk of bleeding between groups, while the other found a significantly increased bleeding risk associated with therapeutic anticoagulation. Conclusion: Among pregnant women anticoagulated for VTE, the reported bleeding risk is variable. The ability to draw definite conclusions is limited by the scarcity and low quality of the studies, the small number of included patients, and the heterogeneity of bleeding definitions used. Large-scale studies with standardized bleeding definitions are required to provide acute bleeding estimates and optimize the care of these patients. Systematic Review Registration: PROSPERO, CRD42021276771.

Severe and critical COVID-19 in pregnancy: A case series from Montreal.

BACKGROUND: Optimal obstetric management for women with coronavirus disease (COVID-19) is not known. We describe the management of six pregnant women requiring in-hospital care for severe COVID-19. METHODS: A retrospective chart review was conducted to identify pregnant women who tested positive for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) between 15 March and 30 June 2020. A subset of women meeting criteria for severe COVID-19 was included. RESULTS: Four women required non-invasive supplemental oxygen therapy and two required mechanical ventilation. Four women were discharged from hospital undelivered and two required preterm delivery. One woman had a pulmonary embolism, and two required re-admission for worsening symptoms. CONCLUSION: Management of pregnant women with severe COVID-19 is complex and should involve multidisciplinary expertise. Avoiding early delivery may be a safe option. We recommend an individualized approach to care, including careful consideration of the expected risks and benefits of expectant obstetric management versus delivery.

The role of echocardiography in amniotic fluid embolism: a case series and review of the literature.

PURPOSE: Amniotic fluid embolism (AFE) is a rare, but often fatal condition characterized by sudden hemodynamic instability and coagulopathy occurring during labour or in the early postpartum period. As the mechanisms leading to shock and the cardiovascular effects of AFE are incompletely understood, the purpose of this case series is to describe how AFE presents on echocardiography and review limited reports in the literature. CLINICAL FEATURES: We describe three cases of AFE at the Jewish General Hospital, a tertiary care centre in Montreal, Canada. All cases met the Clark diagnostic criteria, which comprise 1) sudden cardiorespiratory arrest or both hypotension and respiratory compromise, 2) disseminated intravascular coagulation, 3) clinical onset during labour or within 30 min of delivery of the placenta, and 4) absence of fever. Two patients had a cardiac arrest and the third developed significant hypotension and hypoxia. In all patients, point-of-care echocardiography at the time of shock revealed signs of right ventricular failure including a D-shaped septum, acute pulmonary hypertension, and right ventricular systolic dysfunction. CONCLUSION: This case series and literature review of AFE emphasizes the importance of echocardiography in elucidating the etiology of maternal shock. The presence of right ventricular failure may be considered an important criterion to diagnose AFE.

RéSUMé: OBJECTIF: L'embolie de liquide amniotique (ELA) est une complication rare mais souvent fatale caractérisée par une instabilité hémodynamique et une coagulopathie soudaines survenant pendant le travail obstétrical ou au début de la période postpartum. Étant donné que les mécanismes menant au choc et les effets cardiovasculaires de l'ELA ne sont que partiellement compris, le but de cette série de cas était de décrire comment l'ELA apparaît à l'échocardiographie et de passer en revue les rares comptes rendus dans la littérature. CARACTéRISTIQUES CLINIQUES: Nous décrivons trois cas d'ELA survenus à l'Hôpital général juif, un centre tertiaire de soins à Montréal, au Canada. Tous les cas remplissaient les critères diagnostiques de Clark, qui comportent 1) un arrêt cardiorespiratoire soudain ou une hypotension accompagnée d'une détresse respiratoire, 2) une coagulation intravasculaire disséminée, 3) une apparition clinique pendant le travail obstétrical ou dans un délai de 30 minutes suivant la délivrance du placenta, et 4) l'absence de fièvre. Deux patientes ont subi un arrêt cardiaque et le tiers des patientes ont manifesté une hypotension et une hypoxie significatives. Chez toutes les patientes, l'échocardiographie au chevet au moment du choc a révélé des signes d'insuffisance ventriculaire droite, y compris un septum en forme de D, une hypertension pulmonaire aiguë et une dysfonction systolique ventriculaire droite. CONCLUSION: Cette série de cas et revue de littérature de l'ELA souligne l'importance de l'échocardiographie pour élucider l'étiologie du choc maternel. La présence d'une insuffisance ventriculaire droite peut être considérée un critère important pour diagnostiquer une ELA.

Spurious point-of-care lactate elevation in ethylene glycol intoxication: rediscovering a clinical pearl.

A 76-year-old man was found unresponsive and brought to the emergency department. Initial workup showed profound lactic acidosis on a point-of-care arterial blood gas, without clinical signs of hypoperfusion. Investigations for types A and B lactic acidosis revealed no unifying diagnosis to explain both his altered mental status and profound lactic acidosis. A toxicology workup revealed an increased osmolar gap and an elevated ethylene glycol level. The lactic acidosis and his mental status completely normalised within 8 hours of renal replacement therapy initiation and fomepizole administration. Ethylene glycol metabolites have similar molecular structure with L-lactate. Some blood gas analysers are unable to differentiate them, resulting in an artefactual lactate elevation. Our case highlights the importance of recognising a falsely elevated lactate, which should raise clinical suspicion of ethylene glycol poisoning, as the treatment is time-sensitive to prevent complications and mortality.

A Paralyzing Case of Myalgias.

BACKGROUND Myalgia, which describes muscle pain or soreness, is a common presenting complaint encountered in the Emergency Department, in inpatient settings and in outpatient settings. Its differential diagnosis is broad and includes benign as well as more serious clinical entities. Some of the common causes of myalgias include viral infections, strenuous exercise, and medications. Succinylcholine is a well-known neuromuscular blockade agent that is frequently used for rapid sequence intubation and short surgeries. CASE REPORT We present the case of a 70-year-old male who presented to the Emergency Department with a chief complaint of acute, severe onset diffuse myalgia leading to the inability to mobilize. He was being investigated for recent onset generalized lymphadenopathy and had undergone a diagnostic lymph node biopsy under general anesthesia 2 days prior to his presentation. He was diagnosed with presumed succinylcholine-induced myalgias after other etiologies were deemed less likely with thorough history, physical examination, and laboratory investigations. Succinylcholine binds nicotinic acetylcholine receptors of the neuromuscular junction and produces prolonged depolarization during which activation of the muscle is blocked. Initial depolarization of the neuromuscular junction induces hectic fasciculation of the muscle fibers, which in turn may be responsible for the occurrence of post-operative myalgias (POM). This entity can be severe and debilitating and is self-limited. CONCLUSIONS Succinylcholine remains a commonly used agent in anesthesia and succinylcholine-induced myalgia should remain in the differential diagnosis of acute, non-inflammatory myalgia. Its recognition can help avoid unwarranted, possibly invasive investigations and their associated additional healthcare costs.

Delayed time to emergency hip surgery in patients taking oral anticoagulants.

INTRODUCTION: Surgical intervention within 48 h of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with vitamin K antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. MATERIALS AND METHODS: We conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. RESULTS: A total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 h (IQR: 50-84)] and in the DOAC group [(61 h; IQR: 42 to 77)] versus the No OAC group [44 h (IQR: 28-63), p = 0.0006 and p = 0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p = 0.6396). CONCLUSION: Patients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. Future studies aimed at examining this relationship more closely are warranted. In the meantime, an action plan aimed at early identification and appropriate management of anticoagulation in this vulnerable group of patients is necessary.

NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity.

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1-/- mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.

NLRX1 Enhances Glutamate Uptake and Inhibits Glutamate Release by Astrocytes.

Uptake of glutamate from the extracellular space and glutamate release to neurons are two major processes conducted by astrocytes in the central nervous system (CNS) that protect against glutamate excitotoxicity and strengthen neuronal firing, respectively. During inflammatory conditions in the CNS, astrocytes may lose one or both of these functions, resulting in accumulation of the extracellular glutamate, which eventually leads to excitotoxic neuronal death, which in turn worsens the CNS inflammation. NLRX1 is an innate immune NOD-like receptor that inhibits the major inflammatory pathways. It is localized in the mitochondria and was shown to inhibit cell death, enhance ATP production, and dampen oxidative stress. In the current work, using primary murine astrocyte cultures from WT and Nlrx1-/- mice, we demonstrate that NLRX1 potentiates astrocytic glutamate uptake by enhancing mitochondrial functions and the functional activity of glutamate transporters. Also, we report that NLRX1 inhibits glutamate release from astrocytes by repressing Ca2+-mediated glutamate exocytosis. Our study, for the first time, identified NLRX1 as a potential regulator of glutamate homeostasis in the CNS.

Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release.

Glutamate is one of the most prevalent neurotransmitters released by excitatory neurons in the central nervous system (CNS); however, residual glutamate in the extracellular space is, potentially, neurotoxic. It is now well-established that one of the fundamental functions of astrocytes is to uptake most of the synaptically-released glutamate, which optimizes neuronal functions and prevents glutamate excitotoxicity. In the CNS, glutamate clearance is mediated by glutamate uptake transporters expressed, principally, by astrocytes. Interestingly, recent studies demonstrate that extracellular glutamate stimulates Ca2+ release from the astrocytes' intracellular stores, which triggers glutamate release from astrocytes to the adjacent neurons, mostly by an exocytotic mechanism. This released glutamate is believed to coordinate neuronal firing and mediate their excitatory or inhibitory activity. Therefore, astrocytes contribute to glutamate homeostasis in the CNS, by maintaining the balance between their opposing functions of glutamate uptake and release. This dual function of astrocytes represents a potential therapeutic target for CNS diseases associated with glutamate excitotoxicity. In this regard, we summarize the molecular mechanisms of glutamate uptake and release, their regulation, and the significance of both processes in the CNS. Also, we review the main features of glutamate metabolism and glutamate excitotoxicity and its implication in CNS diseases.