Applications of Urinary Extracellular Vesicles in the Diagnosis and Active Surveillance of Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.

Suboptimal self-reported sleep efficiency and duration are associated with faster accumulation of brain amyloid beta in cognitively unimpaired older adults.

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (Aß) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain Aß measured over a minimum of three time points (range 33.3-72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration <6 hours, in APOE ε4 carriers, and sleep efficiency <65%, in the whole sample and APOE ε4 non-carriers, is associated with faster accumulation of brain Aß. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (Aß) accumulation.Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype.Sleep duration <6 hours is associated with faster brain Aß accumulation in APOE ε4 carriers.Sleep efficiency < 65% is associated with faster brain Aß accumulation in APOE ε4 non-carriers.Personalized sleep interventions should be studied for potential to slow Aß accumulation.

Assessing social vulnerabilities of salivary gland cancer care, prognosis, and treatment in the United States.

BACKGROUND: Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities. METHODS: Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt. RESULTS: Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds of primary surgery (0.89, 0.84, 0.94), radiotherapy (0.91, 0.85, 0.97, p = 0.003) for SGCs. Trends were differentially correlated with SES, ML, HH, and HT-vulnerabilities. CONCLUSIONS: Through quantifying SDoH-derived SGC-disparities, the SVI can guide targeted initiatives against SDoH that elicit the most detrimental associations for specific sociodemographics.

Experiences and resultant care gaps among women with HIV in Canada: concept mapping the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) findings.

OBJECTIVES: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps. DESIGN: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS. SETTING: British Columbia, Ontario and Quebec, Canada. PARTICIPANTS: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers. RESULTS: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV. CONCLUSIONS: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV.

Inhibitors of Inorganic Polyphosphate and Nucleic Acids Attenuate in vitro Thrombin Generation in Plasma from Trauma Patients.

BACKGROUND: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8) and universal heparin reversal agent 8 (UHRA-8). METHODS: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 µg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, p < 0.05 significant. RESULTS: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], p < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], p = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], p = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], p < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], p < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all p < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, p < 0.001). CONCLUSION: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.

Agile response to critical need for clinical trial accessibility during the first COVID-19 pandemic wave.

This article discusses some of the major challenges that the clinical research community faced during the early days of the coronavirus disease 2019 pandemic. A model is offered that may assist other institutions while planning for future pandemics or disasters.

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

The impact of exercise on blood-based biomarkers of Alzheimer's disease in cognitively unimpaired older adults.

Physical activity is a promising preventative strategy for Alzheimer's disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer's disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (Aß42, Aß40, Aß42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition. Ninety-nine community-dwelling older adults (69.1 ± 5.2) were allocated to an inactive control, or to moderate or high intensity exercise groups where they cycled twice weekly for six months. At baseline and six months (post-intervention), fasted blood was collected and analysed using single molecule array (SIMOA) assays, and cognition was assessed. Results demonstrated no change in levels of any plasma biomarker from pre- to post-intervention. At baseline, higher NfL was associated with poorer cognition (ß = -0.33, SE = 0.13, adjusted p = .042). Exploratory analyses indicated higher cardiorespiratory fitness was associated with higher NfL and GFAP levels in apolipoprotein E (APOE) ε4 non-carriers compared to ε4 carriers (NfL, ß = -0.43, SE = 0.19, p = .029; GFAP, ß = -0.41, SE = 0.20, p = .044), though this association was mediated by body mass index (BMI). These results highlight the importance of considering BMI in analysis of blood-based biomarkers, especially when investigating differences between APOE ε4 carriers and non-carriers. Our results also indicate that longer follow-up periods may be required to observe exercise-induced change in blood-based biomarkers.

External Trigger Free Charge Switchable Cationic Ligands in the Design of Safe and Effective Universal Heparin Antidote.

Thrombosis, the formation of blood clots within a blood vessel, can lead to severe complications including pulmonary embolism, cardiac arrest, and stroke. The most widely administered class of anticoagulants is heparin-based anticoagulants such as unfractionated heparin, low-molecular weight heparins (LMWHs), and fondaparinux. Protamine is the only FDA-approved heparin antidote. Protamine has limited efficacy neutralizing LMWHs and no reversal activity against fondaparinux. The use of protamine can lead to complications, including excessive bleeding, hypotension, and hypersensitivity, and has narrow therapeutic window. In this work, a new concept in the design of a universal heparin antidote: switchable protonation of cationic ligands, is presented. A library of macromolecular polyanion inhibitors (MPIs) is synthesized and screened to identify molecules that can neutralize all heparins with high selectivity and reduced toxicity. MPIs are developed by assembling cationic binding groups possessing switchable protonation states onto a polymer scaffold. By strategically selecting the identity and modulating the density of cationic binding groups on the polymer scaffold, a superior universal heparin reversal agent is developed with improved heparin-binding activity and increased hemocompatibility profiles leading to minimal effect on hemostasis. The activity of this heparin antidote is demonstrated using in vitro and in vivo studies.

Theoretical explanations and the availability of information for learning via combined action observation and motor imagery: a commentary on Eaves et al. (2022).

The recent review by Eaves et al. (Psychological Research/Psychologische Forschung, 2022) outlines the research conducted to-date on combined action-observation and motor imagery (AOMI), and more specifically, its added benefit to learning. Of interest, these findings have been primarily attributed to the dual action simulation hypothesis, whereby AO and MI activate separable representations for action that may be later merged when they are congruent with one another. The present commentary more closely evaluates this explanation. What's more, we offer an alternative information-based argument where the benefit to learning may be served instead by the availability of key information. Along these lines, we speculate on possible future directions including the need for a transfer design.

Influence of Social Vulnerability in Treatment and Prognosis of Squamous Cell Carcinoma of the Tongue.

OBJECTIVE: To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real-world contribution of specific disparities. STUDY DESIGN: Retrospective cohort study. SETTING: United States. METHODS: The Centers for Disease Control and Prevention-Social Vulnerability Index (SVI) and National Cancer Institute-Surveillance, Epidemiology, and End Results Program database were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow-up and survival across social vulnerability and 4 subcategories of social vulnerability. RESULTS: As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow-up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores. CONCLUSION: Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.

Survival, Growth, and Toxin Production of Bacillus cereus During Cooking and Storage of Fresh Rice Noodles.

Retail stores maintain fresh rice noodles (FRNs) at room temperature because refrigeration negatively impacts FRNs' texture. The room temperature and high water activity of FRNs help spore-forming Bacillus cereus to grow and produce toxins. In this study, the effect of steam cooking on survival and different storage temperatures on the growth and enterotoxins production of B. cereus in FRNs were investigated. White rice flour was used to make FRNs. Three treatments of FRNs were used in this study; uninoculated, inoculated (with 4.0 log CFU/ml of B. cereus spores), and autoclaved as a negative control. A slurry of rice flour, cornstarch, and water was steam cooked for 4 min at 90°C and incubated for 168 h at 4°C, and for 72 h at 22 and 32°C. Incubated FRNs were tested for pH, B. cereus growth, and enterotoxins production. Steam cooking reduced the total number of B. cereus spores by 0.7 ± 0.3 log CFU/g. Surviving B. cereus spores in inoculated and uninoculated FRNs germinated over 72 h of storage. No B. cereus was detected in negative controls. An interaction was observed across storage temperatures and time (p < 0.05). The B. cereus population in uninoculated FRNs increased by more than 7.0 log CFU/g at 22 and 32°C over 72 h, while inoculated FRNs showed a 5.0 log bacterial increase at these storage temperatures. No growth was observed at 4°C in both inoculated and uninoculated FRNs. The pH of inoculated FRNs was reduced from 6.9 ± 0.1 to 5.7 ± 0.0 at 32°C and to 6.2 ± 0.1 at 22°C, and the pH of uninoculated FRNs was reduced from 7.0 ± 0.1 to 5.8 ± 0.2 at 32°C and to 6.5 ± 0.0 at 22°C, indicative of FRNs spoilage. B. cereus in inoculated FRNs produced enterotoxins after 12 h of storage at 32°C, and over 24 h of storage at 22°C, while no toxin was detected at 4°C. Our findings show that storing FRNs at room temperature for 24 h leads to enterotoxin production, emphasizing the importance of proper FRN storage and their potential risk to consumers. Nevertheless, further research should investigate the effect of other foodborne pathogens on these products.

Developing "The Health After Cancer Podcast" to amplify cancer survivors' voices through digital storytelling.

BACKGROUND: Cancer survivors experience complex medical and psychosocial challenges after a cancer diagnosis, leading to unmet informational and emotional needs. There is a paucity of cancer survivorship educational resources co-created by survivors and medical professionals. OBJECTIVE: Our aim was to create an educational resource for cancer survivors, caregivers, and medical professionals that would leverage digital storytelling to address survivorship topics. PATIENT INVOLVEMENT: Our content and production team included cancer survivors, clinicians, educators, and design experts. All content was co-created by cancer survivors and medical experts. METHODS: We conducted an environmental scan of existing cancer survivorship educational resources in academic and public domains. Applying human-centered design principles, we incorporated patient perspectives through advisory board meetings and focus groups and identified a podcast as the preferred medium. We selected content and speakers, produced the podcast, and developed a corresponding website. RESULTS: Based on patient recommendations, podcast episodes address mental health, fear of cancer recurrence, relationships, parenting, relating to a new body, care transitions for adult survivors of childhood cancer, disclosing health information, and financial burden of cancer. Podcast guests were invited based on lived or learned experience in these domains. Thirteen guests (survivors, experts) and four hosts (two cancer survivors, two oncologists) co-created 15 podcast episodes. Podcast guests found the storytelling experience to be powerful and therapeutic. DISCUSSION: Digital storytelling is a scalable and accessible educational tool for communicating complex survivorship concepts that can amplify survivors' voices and increase awareness among survivors and clinicians. Co-creation of educational resources for cancer survivorship by survivors and professionals is a feasible and innovative educational strategy. PRACTICAL VALUE: A podcast created by and for cancer survivors in partnership with medical experts highlights opportunities for peer-to-peer digital storytelling to foster community among survivors and caregivers. FUNDING: Podcast production was supported by the Stanford Comprehensive Cancer Center.

Assessment of social vulnerability impact in care and prognosis of sinonasal cancers in the United States.

KEY POINTS: Social determinants of health interactively influence sinonasal cancer care and prognosis. Housing-transportation and socioeconomic status showed the largest associations with disparities. The social vulnerability index can reveal the social determinants of sinonasal cancers.

The Role of Diet and Gut Microbiota in Alzheimer's Disease.

Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (Aß) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer's disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of Aß, the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut-brain axis (GBA) in the context of AD progression and pathology have yielded inconsistent findings. This review aims to enhance our understanding of microbial diversity at the species level and the role of these species in AD pathology. Additionally, this review addresses the influence of confounding elements, including diet, probiotics, and prebiotics, on AD throughout different stages (preclinical, mild cognitive impairment (MCI), and AD) of its progression.

Cancer Survivorship at Stanford Cancer Institute.

The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement. Cross-cutting areas of expertise include the following: (a) adolescents and young adults (AYAs), (b) mental health and patient self-management, (c) integration of primary care, and (d) postgraduate medical education. The clinical care model includes embedded survivorship clinics within disease groups in outpatient clinics, novel clinics designed to address unmet needs such as sexual health for women, and primary care-based faculty-led survivorship clinics for patients undergoing active cancer care requiring co-management, those who have completed active therapy and those at high risk for cancer due to genetic risk. Educational initiatives developed to date include an online course and medical textbook for primary care clinicians, a lecture series, monthly research team meetings, and rotations for medical trainees. Patient-facing activities include webinars and a podcast series designed to promote awareness, thus expanding the provision of expert-vetted information. Ongoing research focuses on oncofertility and family building after cancer, improving communication for AYAs, changing mindsets to improve quality of life through targeted digital interventions, increasing capacity to care for cancer survivors, and strengthening collaboration with community partners. IMPLICATIONS FOR CANCER SURVIVORS: Stanford's Cancer Survivorship Program includes a robust transdisciplinary and interdisciplinary research, training and clinical platform that is committed to advancing access and improving care for people living with and beyond cancer, through innovation in design and care delivery.

Metacognitive Exam Preparation Assignments in an Introductory Biology Course Improve Exam Scores for Lower ACT Students Compared with Assignments that Focus on Terms.

Preparing for exams in introductory biology classrooms is a complex metacognitive task. Focusing on lower achieving students (those with entering ACT scores below the median at our institution), we compared the effect of two different assignments distributed ahead of exams by dividing classes in half to receive either terms to define or open-ended metacognitive questions. Completing metacognitive assignments resulted in moderately higher exam scores for students on the second and third exams. Metacognitive assignments also improved accuracy (difference between predicted and actual exam scores) for the second and third exam in lower ACT students, but that improvement was driven largely by higher exam scores in the metacognitive group. Thus, despite the fact that the metacognitive assignments specifically asked students to reflect on their previous exam performance, their previous estimates and predict how well they expected to perform on the exam they were preparing for, there was little evidence that these assignments influenced lower achieving students' confidence levels any more than assignments where students defined terms. While understanding relevant terms was certainly important in this course, these results highlight that open-ended metacognitive prompts may improve exam scores in some students in introductory biology classrooms.

Flagella are required to coordinately activate competition and host colonization factors in response to a mechanical signal.

Bacteria employ antagonistic strategies to eliminate competitors of an ecological niche. Contact-dependent mechanisms, such as the type VI secretion system (T6SS), are prevalent in host-associated bacteria, yet we know relatively little about how T6SS+ strains make contact with competitors in highly viscous environments, such as host mucus. To better understand how cells respond to and contact one another in such environments, we performed a genome-wide transposon mutant screen of the T6SS-wielding beneficial bacterial symbiont, Vibrio fischeri, and identified two sets of genes that are conditionally required for killing. LPS/capsule and flagellar-associated genes do not affect T6SS directly and are therefore not required for interbacterial killing when cell contact is forced yet are necessary for killing in high-viscosity liquid (hydrogel) where cell-cell contact must be biologically mediated. Quantitative transcriptomics revealed that V. fischeri significantly increases expression of both T6SS genes and cell surface modification factors upon transition from low- to high-viscosity media. Consistent with coincubation and fluorescence microscopy data, flagella are not required for T6SS expression in hydrogel. However, flagella play a key role in responding to the physical environment by promoting expression of the surface modification genes identified in our screen, as well as additional functional pathways important for host colonization including uptake of host-relevant iron and carbon sources, and nitric oxide detoxification enzymes. Our findings suggest that flagella may act as a mechanosensor for V. fischeri to coordinately activate competitive strategies and host colonization factors, underscoring the significance of the physical environment in directing complex bacterial behaviors.

Extracorporeal membrane oxygenation for COVID-19-associated severe acute respiratory distress syndrome in Canada: Analysis of data from the Canadian Nosocomial Infection Surveillance Program.

Background: Extracorporeal membrane oxygenation (ECMO) for COVID-19 across Canada has not been well-described. We studied trends for patients with COVID-19-related acute respiratory distress syndrome who received ECMO. Methods: Multicentre retrospective cohort study using data from the Canadian Nosocomial Infection Surveillance Program across four different waves. Surveillance data was collected between March 2020 and June 2022. We reported data stratified by ECMO status and wave. Results: ECMO recipients comprised 299 (6.8%) of the 4,408 critically ill patients included. ECMO recipients were younger (median age 49 versus 62 years, p < 0.001), less likely to be vaccinated against COVID-19 (Wave 4 data: 5.3% versus 19%; p = 0.002), and had fewer comorbidities compared to patients who did not receive ECMO. Thirty-day all-cause mortality was similar between the ECMO and non-ECMO groups (23% versus 26%; p = 0.25). Among ECMO recipients, mortality tended to decrease across Waves 1 to 4: 48%, 31%, 18%, and 16%, respectively (p = 0.04 for trend). However, this was no longer statistically significant when removing the high mortality during Wave 1 (p = 0.15). Conclusions: Our findings suggest that critically ill patients in Canadian hospitals who received ECMO had different characteristics from those who did not receive ECMO. We also observed a trend of decreased mortality over the waves for the ECMO group. Possible explanatory factors may include potential delay in ECMO initiation during Wave 1, evolution of the virus, better understanding of COVID-19 disease and ECMO use, and new medical treatments and vaccines available in later waves. These findings may provide insight for future potential pandemics.

Historique: L'oxygénation extracorporelle en cas de COVID-19 n'est pas bien décrite au Canada. Les chercheurs ont étudié les tendances des patients ayant un syndrome respiratoire aigu lié à la COVID-19 qui ont reçu une oxygénation extracorporelle. Méthodologie: Étude de cohorte rétrospective multicentrique à l'aide de données du Programme canadien de surveillance des infections nosocomiales lors de quatre différentes vagues. Les chercheurs ont recueilli les données de surveillance de mars 2020 à juin 2022. Ils ont rendu compte des données stratifiées en fonction de l'état d'oxygénation extracorporelle et de la vague. Résultats: Les receveurs d'une oxygénation extracorporelle représentaient 299 (6,8 %) des 4 408 patients participants gravement malades. Ils étaient plus jeunes (âge médian de 49 ans par rapport à 62 ans, p<0,001), moins susceptibles d'être vaccinés contre la COVID-19 (données de la quatrième vague 4 : 5,3 % par rapport à 19 %; p=0,002) et présentaient moins d'autres maladies que les patients qui avaient reçu une oxygénation extracorporelle. La mortalité toutes causes confondues au bout de 30 jours était semblable entre le groupe sous oxygénation extracorporelle et celui sans oxygénation extracorporelle (23 % par rapport à 26 %; p=0,25). Chez les receveurs d'une oxygénation extracorporelle, la mortalité avait tendance à diminuer d'une vague à l'autre, soit de 48 %, 31 %, 18 % et 16 % entre la première et la quatrième vague, respectivement (p=0,04 par tendance). Cependant, ces résultats n'étaient plus statistiquement significatifs lorsqu'on excluait le taux de mortalité élevé observé pendant la première vague (p=0,15). Conclusions: Selon les observations des chercheurs, les patients gravement malades des hôpitaux canadiens qui avaient reçu une oxygénation extracorporelle présentaient des caractéristiques différentes de ceux qui n'en avaient pas reçu. Dans le groupe sous oxygénation extracorporelle, ils ont également observé une tendance vers une diminution de la mortalité entre les vagues. Les facteurs explicatifs possibles peuvent inclure un retard potentiel de l'initiation de l'oxygénation extracorporelle pendant la première vague, l'évolution du virus, une meilleure compréhension de la COVID-19, le recours à l'oxygénation extracorporelle, les nouveaux traitements médicaux et les vaccins offerts lors de vagues plus tardives. Ces observations pourraient donner des indications intéressantes lors de futures pandémies. Summary: COVID-19 has affected millions of people. Some patients with COVID-19 develop extremely severe disease requiring advanced critical care. Extracorporeal Membrane Oxygenation (ECMO) is an advanced potentially life-saving technique that can support patients whose lungs are unable to function properly despite using a ventilator (breathing machine). ECMO temporarily takes over lung function, essentially acting as external lungs. ECMO can allow time for the body to heal and potentially improve survival for patients with severe lung failure. The decision to use ECMO is complex and always made by a team of medical professionals who factor in the patient's overall health, medical conditions, and disease severity.We studied the trends for critically ill patients with COVID-19 who received ECMO across Canadian hospitals. We used data collected by trained health care professionals through a Canada-wide program that monitors infections in Canadian hospitals. We compared data between critically ill patients who received and did not receive ECMO, and by wave of the COVID-19 pandemic.Our data found that critically ill patients who received ECMO tended to be younger, have fewer medical conditions, and be less likely to be vaccinated against COVID-19. For patients who received ECMO, the mortality was highest in Wave 1 (48%), then Wave 2 (31%), and similar during Waves 3 and 4 (18% and 16%, respectively). Possible explanations for this trend include potential ECMO delay in Wave 1, the evolution of the virus, a better understanding of ECMO use for COVID-19 and available treatments and vaccines during later waves.In conclusion, our study highlights that critically ill patients who received ECMO in Canada had different features and traits compared to those who did not receive ECMO. As well, our study reported mortality across the waves, with possible explanations for the findings offered. These trends may be helpful in providing insight for future potential pandemics.