Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

Early Ultrasound Surveillance of Newly-Created Hemodialysis Arteriovenous Fistula

Introduction: We assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomised controlled trial (RCT) evaluation of ultrasounddirected salvage intervention. Methods: Consenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF non-maturation identified by logistic regression modelling. Results: Of 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF non-maturation could be optimally modelled from the week four ultrasound parameters alone, but with only moderate positive predictive values (wrist, 60.6% (95% CI 43.9 – 77.3); elbow, 66.7% (48.9 - 84.4)). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modelling of the early ultrasound characteristics could also predict primary patency failure at 6 months, but that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data. Conclusions: Early ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

From Sea to Sea: Canada's Three Oceans of Biodiversity

Evaluating and understanding biodiversity in marine ecosystems are both necessary and challenging for conservation. This paper compiles and summarizes current knowledge of the diversity of marine taxa in Canada's three oceans while recognizing that this compilation is incomplete and will change in the future. That Canada has the longest coastline in the world and incorporates distinctly different biogeographic provinces and ecoregions (e.g., temperate through ice-covered areas) constrains this analysis. The taxonomic groups presented here include microbes, phytoplankton, macroalgae, zooplankton, benthic infauna, fishes, and marine mammals. The minimum number of species or taxa compiled here is 15,988 for the three Canadian oceans. However, this number clearly underestimates in several ways the total number of taxa present. First, there are significant gaps in the published literature. Second, the diversity of many habitats has not been compiled for all taxonomic groups (e.g., intertidal rocky shores, deep sea), and data compilations are based on short-term, directed research programs or longer-term monitoring activities with limited spatial resolution. Third, the biodiversity of large organisms is well known, but this is not true of smaller organisms. Finally, the greatest constraint on this summary is the willingness and capacity of those who collected the data to make it available to those interested in biodiversity meta-analyses. Confirmation of identities and intercomparison of studies are also constrained by the disturbing rate of decline in the number of taxonomists and systematists specializing on marine taxa in Canada. This decline is mostly the result of retirements of current specialists and to a lack of training and employment opportunities for new ones. Considering the difficulties encountered in compiling an overview of biogeographic data and the diversity of species or taxa in Canada's three oceans, this synthesis is intended to serve as a biodiversity baseline for a new program on marine biodiversity, the Canadian Healthy Ocean Network. A major effort needs to be undertaken to establish a complete baseline of Canadian marine biodiversity of all taxonomic groups, especially if we are to understand and conserve this part of Canada's natural heritage

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Ocean Acidification Mitigates the Negative Effects of Increased Sea Temperatures on the Biomineralization and Crystalline Ultrastructure of Mytilus

Negative impacts of global climate change are predicted for a range of taxa. Projections predict marked increases in sea surface temperatures and ocean acidification (OA), arguably placing calcifying organisms at most risk. While detrimental impacts of environmental change on the growth and ultrastructure of bivalve mollusk shells have been shown, rapid and diel fluctuations in pH typical of coastal systems are often not considered. Mytilus edulis, an economically important marine calcifier vulnerable to climate change, were exposed to current and future OA (380 and 1000 ppm pCO2), warming (17 and 20°C), and ocean acidification and warming (OAW) scenarios in a seawater system incorporating natural fluctuations in pH. Both macroscopic morphometrics (length, width, height, volume) and microscopic changes in the crystalline structure of shells (ultrastructure) using electron backscatter diffraction (EBSD) were measured over time. Increases in seawater temperature and OAW scenarios led to increased and decreased shell growth respectively and on marginal changes in cavity volumes. Shell crystal matrices became disordered shifting toward preferred alignment under elevated temperatures indicating restricted growth, whereas Mytilus grown under OAW scenarios maintained single crystal fabrics suggesting OA may ameliorate some of the negative consequences of temperature increases. However, both elevated temperature and OAW led to significant increases in crystal size (grain area and diameter) and misorientation frequencies, suggesting a propensity toward increased shell brittleness. Results suggest adult Mytilus may become more susceptible to biological determinants of survival in the future, altering ecosystem structure and functioning

Cellular Immune Responses to SARS-CoV-2 in Exposed Seronegative Individuals

Some SARS-CoV-2-exposed individuals develop immunity without overt infection. We identified 11 individuals who were negative by nucleic acid testing during prolonged close contact and with no serological diagnosis of infection. As this could reflect natural immunity, cross-reactive immunity from previous coronavirus exposure, abortive infection due to de novo immune responses, or other factors, our objective was to characterize immunity against SARS-CoV-2 in these individuals. Blood was processed into plasma and peripheral blood mononuclear cells (PBMC) and screened for IgG, IgA, and IgM antibodies (Ab) against SARS-CoV-2 and common β-coronaviruses OC43 and HKU1. Receptor blocking activity and interferon-alpha (IFN-α) in plasma were also measured. Circulating T cells against SARS-CoV-2 were enumerated and CD4+ and CD8+ T cell responses discriminated after in vitro stimulation. Exposed uninfected individuals were seronegative against SARS-CoV-2 spike (S) and selectively reactive against OC43 nucleocapsid protein (N), suggesting common β-coronavirus exposure induced Ab cross-reactive against SARS-CoV-2 N. There was no evidence of protection from circulating angiotensin-converting enzyme (ACE2) or IFN-α. Six individuals had T cell responses against SARS-CoV-2, with four involving CD4+ and CD8+ T cells. We found no evidence of protection from SARS-CoV-2 through innate immunity or immunity induced by common β-coronaviruses. Cellular immune responses against SARS-CoV-2 were associated with time since exposure, suggesting that rapid cellular responses may contain SARS-CoV-2 infection below the thresholds required for a humoral response

Characteristics of Vaccine- and Infection-Induced Systemic IgA Anti-SARS-CoV-2 Spike Responses

Mucosal IgA is widely accepted as providing protection against respiratory infections, but stimulation of mucosal immunity, collection of mucosal samples and measurement of mucosal IgA can be problematic. The relationship between mucosal and circulating IgA responses is unclear, however, whole blood is readily collected and circulating antigen-specific IgA easily measured. We measured circulating IgA against SARS-CoV-2 spike (S) to investigate vaccine- and infection-induced production and correlation with protection. Circulating IgA against ancestral (Wuhan-Hu-1) and Omicron (BA.1) S proteins was measured at different time points in a total of 143 subjects with varied backgrounds of vaccination and infection. Intramuscular vaccination induced circulating anti-SARS-CoV-2 S IgA. Subjects with higher levels of vaccine-induced IgA against SARS-CoV-2 S (p = 0.0333) or receptor binding domain (RBD) (p = 0.0266) were less likely to experience an Omicron breakthrough infection. The same associations did not hold for circulating IgG anti-SARS-CoV-2 S levels. Breakthrough infection following two vaccinations generated stronger IgA anti-SARS-CoV-2 S responses (p = 0.0002) than third vaccinations but did not selectively increase circulating IgA against Omicron over ancestral S, indicating immune imprinting of circulating IgA responses. Circulating IgA against SARS-CoV-2 S following breakthrough infection remained higher than vaccine-induced levels for over 150 days. In conclusion, intramuscular mRNA vaccination induces circulating IgA against SARS-CoV-2 S, and higher levels are associated with protection from breakthrough infection. Vaccination with ancestral S enacts imprinting within circulating IgA responses that become apparent after breakthrough infection with Omicron. Breakthrough infection generates stronger and more durable circulating IgA responses against SARS-CoV-2 S than vaccination alone

A Paradigm Shift for Rheumatic Heart Disease: Role of Group G Streptococcus

Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection characterised by inflammatory changes to heart, joint, brain, blood vessel and skin tissue. ARF/RHD is considered to be triggered by antibody and T-cell responses against immunodominant GAS virulence factors including M-protein, that cross-react with host tissue proteins. Repeat exposures to GAS perpetuate the autoimmune process leading to permanent cardiac damage. However, in some ARF/RHD endemic regions, there is low carriage of GAS were correspondingly high carriage of Streptococcus dysgalactiae subspecies equisimilis (SDSE), also known as β-hemolytic groups C and G streptococci (GCS/GGS). This has led to the suggestion that SDSE might also have the potential to initiate or exacerbate ARF/RHD. We have discovered using an appropriate model that GGS does indeed cause both myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological and functional changes in the hearts of animals exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin and collagen I were comparable in both GGS and GAS exposed animals providing further evidence that GGS can induce and/or exacerbate ARF/RHD