Search

Jennifer Cogan,1 Maud André,2 Gabrielle Ariano-Lortie,2 Anna Nozza,3 Meggie Raymond,1 Antoine Rochon,1 Grisell Vargas-Shaffer4 1Department of Anesthesiology, Montreal Heart Institute, Université de Montréal, Montreal, QC H1T 1C8, Canada; 2Department of Nursing, Montreal Heart Institute, Montreal, QC H1T 1C8, Canada; 3Montreal Health Innovations Coordinating Center, Montreal Heart Institute, Montreal, QC H1Y 3N1, Canada; 4Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal, Montreal, QC H2X 3E4, CanadaCorrespondence: Jennifer CoganMontreal Heart Institute, 5000 Belanger, Montreal, Quebec H1T 1C8, CanadaTel +1 514-376-3330Fax +1 514-376-8784Email cogan.jennifer@me.comBackground: We conducted a chart review of prospectively collected data in order to demonstrate the safety and efficacy of an innovative technique of pleural and mediastinal drain injections.Methods: Patients who had undergone cardiac surgery and who continued to have pain despite the use of a multimodal pain protocol received injections of 20 mL of 0.25% bupivacaine in pleural and/or mediastinal chest drainage tubes.Results: Patients were evaluated for the incidence mediastinitis, osteitis, and deep sternal wound infection as well as the speed and intensity of pain relief. The odds ratio of infection in the infused group was 0.955 (CI = 0.4705, 1.9384). The adjusted mean “decrease in pain” was 4.01 (SEM = 0.15 and 95% CI = 3.78, 4.38), using the 11-point Likert Numerical Rating Scale. The mean adjusted “time to maximum pain relief” was 8.33 minutes (SEM = 0.42 and 95% CI = 7.50, 9.15).Conclusion: This technique is a powerful, safe, and efficient tool in the armamentarium of pain management and its growing use within our institution has provided a substantial benefit in the treatment of early post-operative pain.Keywords: acute pain service, bupivacaine, cardiac surgery, pain management, pleural drain, safety considerations

Abstract Neuromyelitis optica spectrum disorder is an autoimmune disease, causing severe disability due to relapses, but recent mortality data are limited. Among 396 patients seropositive for anti‐aquaporin‐4 antibody from 2014 to 2020 in the United Kingdom, 39 deaths occurred: 19 (48.7%) were unrelated to disease; 14 (35.9%) were severe disability‐ or relapse‐related; and 4 (10.3%) were attributed to malignancy/infection. Mean annual mortality was 1.92% versus 0.63% in the matched population. The standardized mortality ratio was 3.04 (95% confidence interval 1.67–5.30) with 1.29% excess mortality per year in patients. Median Expanded Disability Status Scale before death was 7.0. Results highlight the importance of preventing relapses that drive disability.

Ixodes scapularis and Ixodes pacificus are vectors of a range of pathogens of public health significance in North America. These ticks transmit pathogens to and from wild animal reservoir host species, but also bite humans and expose them to the pathogens. We describe the geographical and temporal distribution of the pathogen Babesia odocoilei, the causative agent of cervid babesiosis. Ixodes spp. ticks collected through active and passive surveillance were submitted to the National Microbiology Laboratory of the Public Health Agency of Canada for analysis of the presence of B. odocoilei from 2018 to 2021. Generalized linear models were constructed to evaluate the temporal change of B. odocoilei prevalence across Canada. Babesia odocoilei-positive I. scapularis are widespread across south-central and eastern regions of Canada, with an overall prevalence of 12.0 % in both nymphs (CI 95 % : 11.4–12.6) and adults (CI 95 % : 11.9–12.1) collected in passive surveillance and 13.2 % (CI 95 % : 12.9–13.5) and 10.0 % (CI 95 % : 9.8–10.2) in nymphs and adult, respectively, collected in active surveillance. A single I. pacificus tick tested positive in active surveillance out of 29 ticks collected in British Columbia, while no B odocoilei-positive I. scapularis were found in passive surveillance among the 11 adult ticks tested. Although B. odocoilei infection prevalence of adult I. scapularis was significantly higher in 2019 (14.1 %) than in 2018 (7.4 %), it remained stable from 2019 to 2021, suggesting that this pathogen may already be well established in endemic tick populations. The results provided in this article represent, to date, the most comprehensive picture of B. odocoilei distribution and prevalence in ticks in Canada and highlight the interest of maintaining One Health surveillance approaches to give added insight into disease transmission cycles for less well-characterized microorganisms.

Introduction Digital surgical wound monitoring for patients at home is becoming an increasingly common method of wound follow-up. This regular monitoring improves patient outcomes by detecting wound complications early and enabling treatment to start before complications worsen. However, reviewing the digital data creates a new and additional workload for staff. The aim of this study is to assess a surgical wound monitoring platform that uses artificial intelligence to assist clinicians to review patients’ wound images by prioritising concerning images for urgent review. This will manage staff time more effectively.Methods and analysis This is a feasibility study for a new artificial intelligence module with 120 cardiac surgery patients at two centres serving a range of patient ethnicities and urban, rural and coastal locations. Each patient will be randomly allocated using a 1:1 ratio with mixed block sizes to receive the platform with the new detection and prioritising module (for up to 30 days after surgery) plus standard postoperative wound care or standard postoperative wound care only. Assessment is through surveys, interviews, phone calls and platform review at 30 days and through medical notes review and patient phone calls at 60 days. Outcomes will assess safety, acceptability, feasibility and health economic endpoints. The decision to proceed to a definitive trial will be based on prespecified progression criteria.Ethics and dissemination Permission to conduct the study was granted by the North of Scotland Research Ethics Committee 1 (24/NS0005) and the MHRA (CI/2024/0004/GB). The results of this Wound Imaging Software Digital platfOrM (WISDOM) study will be reported in peer-reviewed open-access journals and shared with participants and stakeholders.Trial registration numbers ISRCTN16900119 and NCT06475703.

Introduction Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy–safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed.Methods and analysis LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is ‘effective’ if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or ‘ineffective’ if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety.Ethics and dissemination The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients.Trial registration number NCT05523297.

Summary: Gender equality has been a crosscutting issue in Horizon 2020 with three objectives: gender balance in decision-making, gender balance and equal opportunities in project teams at all levels, and inclusion of the gender dimension in research and innovation content. Between 2017 and 2022, the EU funded, in collaboration with national agencies, 13 transnational projects under “GENDER-NET Plus” that explored how to best integrate both sex and gender into studies ranging from social sciences, humanities, and health research. As the projects neared completion, forty researchers from these interdisciplinary teams met in November 2022 to share experiences, discuss challenges, and consider the best ways forward to incorporate sex and gender in research. Here, we summarize the reflections from this workshop and provide some recommendations for i) how to plan the studies (e.g., how to define sex and/or gender and their dimensions, rationale for the hypotheses, identification of data that can best answer the research question), ii) how to conduct them (e.g., adjust definitions and dimensions, perform pilot studies to ensure proper use of terminology and revise until consensus is achieved), and iii) how to analyze and report the findings being mindful of any real-world impact.

Abstract Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the mechanisms that regulate correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intramolecular rearrangements to achieve the assembly-competent state observed in previous structures. This structural insight provides understanding into the mechanism for regulated self-assembly of the mitochondrial fission machinery.

Abstract The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.

Abstract Cytoglobin is a heme protein with unresolved physiological function. Genetic deletion of zebrafish cytoglobin (cygb2) causes developmental defects in left-right cardiac determination, which in humans is associated with defects in ciliary function and low airway epithelial nitric oxide production. Here we show that Cygb2 co-localizes with cilia and with the nitric oxide synthase Nos2b in the zebrafish Kupffer’s vesicle, and that cilia structure and function are disrupted in cygb2 mutants. Abnormal ciliary function and organ laterality defects are phenocopied by depletion of nos2b and of gucy1a, the soluble guanylate cyclase homolog in fish. The defects are rescued by exposing cygb2 mutant embryos to a nitric oxide donor or a soluble guanylate cyclase stimulator, or with over-expression of nos2b. Cytoglobin knockout mice also show impaired airway epithelial cilia structure and reduced nitric oxide levels. Altogether, our data suggest that cytoglobin is a positive regulator of a signaling axis composed of nitric oxide synthase–soluble guanylate cyclase–cyclic GMP that is necessary for normal cilia motility and left-right patterning.

Background: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia--ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. Aim: To establish consensus on a communication OMI for inclusion in the ROMA COS. Methods & Procedures: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by [greater than or equal to] 70% of participants. Outcomes & Results: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living--3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. Conclusions & Implications: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research.

Background: Discourse analysis has recently received much attention in the aphasia literature. Even if post-stroke language recovery occurs throughout the longitudinal continuum of recovery, very few studies have documented discourse changes from the hyperacute to the chronic phases of recovery. Aims: To document a multilevel analysis of discourse changes from the hyperacute phase to the chronic phase of post-stroke recovery using a series of single cases study designs. Methods & Procedures: Four people with mild to moderate post-stroke aphasia underwent four assessments (hyperacute: 0-24 h; acute: 24-72 h; subacute: 7-14 days; and chronic: 6-12 months post-onset). Three discourse tasks were performed at each time point: a picture description, a personal narrative and a story retelling. Multilevel changes in terms of macro- and microstructural aspects were analysed. The results of each discourse task were combined for each time point. Individual effect sizes were computed to evaluate the relative strength of changes in an early and a late recovery time frame. Outcomes & Results: Macrostructural results revealed improvements throughout the recovery continuum in terms of coherence and thematic efficiency. Also, the microstructural results demonstrated linguistic output improvement for three out of four participants. Namely, lexical diversity and the number of correct information units/min showed a greater gain in the early compared with the late recovery phase. Conclusions & Implications: This study highlights the importance of investigating all discourse processing levels as the longitudinal changes in discourse operate differently at each phase of recovery. Overall results support future longitudinal discourse investigation in people with post-stroke aphasia.

Abstract Objective To identify and synthesize epidemiologic data for preterm labour (PTL) and preterm birth (PTB). Methods A systematic search, with protocol registered in PROSPERO, was implemented in MEDLINE and EMBASE and supplemented by web‐based and grey literature searches. Observational, population‐based studies in the United States, Canada, United Kingdom, France, Germany, Spain, and Italy, published in English between 2012 and 2022 were considered for inclusion. Estimates by country were reported and stratified by gestational age, birth plurality, and race/ethnicity, data permitting. Results Ten publications and nine grey literature reports were included. Epidemiologic estimates of PTL were reported for the United Kingdom and France: PTL was diagnosed in 2.2% of pregnancies and preceded 50% of PTBs. PTB rates were reported for the United States, Canada, United Kingdom, France, and Spain. Among live births in these countries, annual PTB incidence ranged from 5.9% (Spain, 2020) to 10.2% (United States, 2019). Most countries reported the PTB incidence by gestational age; reports by birth plurality or race/ethnicity were scarce. PTB rates for Germany or Italy were not identified. Conclusions While PTBs were well‐reported overall and by gestational age, how rates varied by plurality, race/ethnicity and etiology is unclear. Epidemiologic estimates for PTL, a leading cause of PTB, were rarely reported in the literature. Population‐based research is needed to understand the burden of PTL and for decision making regarding the management of this condition.

BackgroundOrgan and Tissue Donation Coordinators (OTDCs) are key to the success of deceased organ donation processes. However, reduced resilience can leave them susceptible to the incidence of work-related issues and decrease the quality of the care provided. Therefore, this study aimed to examine the extent of resilience and influencing aspects among OTDCs in Canada.MethodsMixed-method (QUAN-qual) explanatory sequential design. Quantitative data was collected using an online cross-sectional survey approach with demographic data and the validated scales and analyzed using descriptive and inferential statistics. Qualitative data was collected using a descriptive approach with a semi-structured interview guide and analyzed using content analysis.ResultsOne hundred twenty participants responded to the survey, and 39 participants were interviewed. Most participants from the survey were female (82%), registered nurses (97%) and on average 42 years old. The quantitative data revealed that OTDCs had a high level of perceived compassion satisfaction (ProQOL-CS = 36.3) but a resilience score (CD-RISC = 28.5) lower than other groups of healthcare professionals. OTDCs with over a year of experience in the role were more likely to have higher levels of resilience. The qualitative data identified that participants saw resilience as crucial for their work-related well-being. Although coping strategies were identified as a key factor that enhance resilience, many OTDCs reported difficulty in developing healthy coping strategies, and that the use of unhealthy mechanisms (e.g., alcohol and smoking) can result in negative physical consequences (e.g., weight gain) and reduced resilience levels.ConclusionParticipants reported using a series of coping and protective strategies to help build resilience, but also difficulty in developing healthy mechanisms. The lack of healthy coping strategies were seen as contributing to negative work-related issues (e.g., burnout). Our findings are being used to develop tailored interventions to improve resilience and healthy coping strategies among organ donor coordinators in Canada.

Summary: The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.

Abstract Identifying vulnerability factors for developing persisting concussion symptoms is imperative for determining which patients may require specialized treatment. Using cross-sectional questionnaire data from an Ontario-wide observational concussion study, we compared patients with acute concussion (≤ 14 days) and prolonged post-concussion symptoms (PPCS) (≥ 90 days) on four factors of interest: sex, history of mental health disorders, history of headaches/migraines, and past concussions. Differences in profile between the two groups were also explored. 110 patients with acute concussion and 96 patients with PPCS were included in our study. The groups did not differ on the four factors of interest. Interestingly, both groups had greater proportions of females (acute concussion: 61.1% F; PPCS: 66.3% F). Patient profiles, however, differed wherein patients with PPCS were significantly older, more symptomatic, more likely to have been injured in a transportation-related incident, and more likely to live outside a Metropolitan city. These novel risk factors for persisting concussion symptoms require replication and highlight the need to re-evaluate previously identified risk factors as more and more concussions occur in non-athletes and different risk factors may be at play.