National influenza mid-season report, 2022-2023: A rapid and early epidemic onset.

Canada's 2022-2023 national influenza epidemic was declared in epidemiological week 43 (week ending October 29, 2022), relatively early in comparison to historical seasons. This year marks the return to pre-pandemic-like influenza circulation, following the brief and delayed influenza epidemic declared in the spring of the 2021-2022 season. To date this season, 59,459 detections of influenza have been reported out of 456,536 tests; both values exceeding historical averages. This epidemic is being fundamentally driven by influenza A, with influenza A(H3N2) accounting for 94% of subtyped detections. This season to date has had a significant impact on adolescents and young children, with a high proportion of detections occurring in those aged 0-19 years (42%). Provinces and territories have reported higher than usual influenza-associated hospitalizations, intensive care unit admissions, and deaths in comparison with previous seasons; in particular, paediatric hospitalization incidence was persistently far above historical peak levels for several weeks. The return of seasonal influenza circulation highlights the importance of sustained vigilance with regard to influenza and employment of available mitigation measures, especially of annual seasonal influenza vaccination.

Syndromic surveillance performance in Canada throughout the COVID-19 pandemic, March 1, 2020 to March 4, 2023.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for robust surveillance of respiratory viruses. Syndromic surveillance continues to be an important surveillance component recommended by the World Health Organization (WHO). While FluWatchers, Canada's syndromic surveillance system, has been in place since 2015, the COVID-19 pandemic provided a valuable opportunity to expand the program's scope and underlying technology infrastructure. Following some structural changes to FluWatchers syndromic questionnaire, participants are now able to contribute valuable data to the non-specific surveillance of respiratory virus activity across Canada. This article examines the performance of FluWatchers' syndromic surveillance over the three years of the COVID-19 pandemic in Canada. More specifically, this article examines FluWatchers' performance with respect to the correlation between the FluWatchers influenza-like illness (ILI) and acute respiratory infection (ARI) indicators and total respiratory virus detections (RVDs) in Canada, including influenza, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other respiratory viruses.

National Influenza Annual Report, Canada, 2022-2023: Canada's first fall epidemic since the 2019-2020 season.

Coinciding with the beginning of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, Canadian seasonal influenza circulation was suppressed, which was a trend reported globally. Canada saw a brief and delayed return of community influenza circulation during the spring of the 2021-2022 influenza season. Surveillance for Canada's 2022-2023 seasonal influenza epidemic began in epidemiological week 35 (week starting August 28, 2022) and ended in epidemiological week 34 (week ending August 26, 2023). The 2022-2023 season marked the return to pre-pandemic-like influenza circulation. The epidemic began in epidemiological week 43 (week ending October 29, 2022) and lasted 10 weeks. Driven by influenza A(H3N2), the epidemic was relatively early, extraordinary in intensity, and short in length. This season, a total of 74,344 laboratory-confirmed influenza detections were reported out of 1,188,962 total laboratory tests. A total of 93% of detections were influenza A (n=68,923). Influenza A(H3N2) accounted for 89% of the subtyped specimens (n=17,638/19,876). Late-season, Canada saw community circulation of influenza B for the first time since the 2019-2020 season. The 2022-2023 influenza season in Canada had an extraordinary impact on children and youth; nearly half (n=6,194/13,729, 45%) of reported influenza A(H3N2) detections were in the paediatric (younger than 19 years) population. Weekly paediatric influenza-associated hospital admissions were persistently above historical peak levels for several weeks. The total number of influenza-associated paediatric hospitalizations (n=1,792) far exceeded historical averages (n=1,091). With the return of seasonal influenza circulation and endemic co-circulation of multiple high burden respiratory viruses, sustained vigilance is warranted. Annual seasonal influenza vaccination is a key public health intervention available to protect Canadians.

Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism.

Lung-resident memory B cells (MBCs) provide localized protection against reinfection in respiratory airways. Currently, the biology of these cells remains largely unexplored. Here, we combined influenza and SARS-CoV-2 infection with fluorescent-reporter mice to identify MBCs regardless of antigen specificity. We found that two main transcriptionally distinct subsets of MBCs colonized the lung peribronchial niche after infection. These subsets arose from different progenitors and were both class switched, somatically mutated, and intrinsically biased in their differentiation fate toward plasma cells. Combined analysis of antigen specificity and B cell receptor repertoire segregated these subsets into "bona fide" virus-specific MBCs and "bystander" MBCs with no apparent specificity for eliciting viruses generated through an alternative permissive process. Thus, diverse transcriptional programs in MBCs are not linked to specific effector fates but rather to divergent strategies of the immune system to simultaneously provide rapid protection from reinfection while diversifying the initial B cell repertoire.

National Influenza Annual Report, Canada, 2021-2022: A brief, late influenza epidemic.

Canadian seasonal influenza circulation had been suppressed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This suppression was reported globally and generated concern that the return of community influenza circulation could be intense and that co-circulation of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was possible and potentially severe. Community circulation of influenza returned to Canada during the 2021-2022 influenza season. The influenza epidemic began in week 16 (mid-April 2022) and lasted only nine weeks. This epidemic was driven by influenza A(H3N2) and was exceptionally late in the season, low in intensity and short in length. Community co-circulation of influenza and SARS-CoV-2 was observed in Canada for the first time during the 2021-2022 seasonal influenza epidemic. The unusual characteristics of the 2021-2022 influenza epidemic suggest that a breadth of factors moderate transmission dynamics of the two viruses. Concerns of an intense seasonal influenza epidemic did not come to fruition during the 2021-2022 season; therefore, high influenza susceptibility remains, as does predisposition to larger influenza epidemics. Ongoing circulation of SARS-CoV-2 creates uncertainty about dynamics of future influenza epidemics, but influenza vaccination remains a key public health intervention available to protect Canadians. Public health authorities need to remain vigilant, maintain surveillance and continue to plan for both heightened seasonal influenza circulation and for the potential for endemic co-circulation of influenza and SARS-CoV-2.

Questions to improve family-staff communication in the ICU: a randomized controlled trial.

PURPOSE: Relatives of intensive care unit (ICU) patients suffer emotional distress that impairs their ability to acquire the information they need from the staff. We sought to evaluate whether providing relatives with a list of important questions was associated with better comprehension on day 5. METHODS: Randomized, parallel-group trial. Relatives of mechanically ventilated patients were included from 14 hospitals belonging to the FAMIREA study group in France. A validated list of 21 questions was handed to the relatives immediately after randomization. The primary endpoint was comprehension on day 5. Secondary endpoints were satisfaction (Critical Care Family Needs Inventory, CCFNI) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). RESULTS: Of 394 randomized relatives, 302 underwent the day-5 assessment of all outcomes. Day-5 family comprehension was adequate in 68 (44.2%) and 75 (50.7%) intervention and control group relatives (P = 0.30), respectively. Over the first five ICU days, median number of family-staff meetings/patient was 6 [3-9], median total meeting time was 72.5 [35-110] min, and relatives asked a median of 20 [8-33] questions including 11 [6-13] from the list, with no between-group difference. Satisfaction and anxiety/depression symptoms were not significantly different between groups. The only variable significantly associated with better day-5 comprehension by multivariable analysis was a higher total number of questions asked before day 5. CONCLUSIONS: Providing relatives with a list of questions did not improve day-5 comprehension, secondary endpoints, or information time. Further research is needed to help families obtain the information they need. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02410538.

Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial.

IMPORTANCE: Observational studies have reported that statin use may be associated with improved outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is associated with substantial mortality. OBJECTIVE: To determine whether statin therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26 intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the first 251 patients. INTERVENTIONS: Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not improve day-28 survival. These findings do not support the use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01057758.

CD36 and SR-BI are involved in cellular uptake of provitamin A carotenoids by Caco-2 and HEK cells, and some of their genetic variants are associated with plasma concentrations of these micronutrients in humans.

Scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36) have been involved in cellular uptake of some provitamin A carotenoids. However, data are incomplete (e.g., there are no data on α-carotene), and it is not known whether genetic variants in their encoding genes can affect provitamin A carotenoid status. The objectives were 1) to assess the involvement of these scavenger receptors in cellular uptake of the main provitamin A carotenoids (i.e., ß-carotene, α-carotene, and ß-cryptoxanthin) as well as that of preformed vitamin A (i.e., retinol) and 2) to investigate the contribution of genetic variations in genes encoding these proteins to interindividual variations in plasma concentrations of provitamin A carotenoids. The involvement of SR-BI and CD36 in carotenoids and retinol cellular uptake was investigated in Caco-2 and human embryonic kidney (HEK) cell lines. The involvement of scavenger receptor class B type I (SCARB1) and CD36 genetic variants on plasma concentrations of provitamin A carotenoids was assessed by association studies in 3 independent populations. Cell experiments suggested the involvement of both proteins in cellular uptake of provitamin A carotenoids but not in that of retinol. Association studies showed that several plasma provitamin A carotenoid concentrations were significantly different (P < 0.0083) between participants who bore different genotypes at single nucleotide polymorphisms and haplotypes in CD36 and SCARB1. In conclusion, SR-BI and CD36 are involved in cellular uptake of provitamin A carotenoids, and genetic variations in their encoding genes may modulate plasma concentrations of provitamin A carotenoids at a population level.

CD36 is involved in lycopene and lutein uptake by adipocytes and adipose tissue cultures.

SCOPE: Carotenoids are mainly stored in adipose tissue. However, nothing is known regarding the uptake of carotenoids by adipocytes. Thus, our study explored the mechanism by which lycopene and lutein, two major human plasma carotenoids, are transported. METHODS AND RESULTS: CD36 was a putative candidate for this uptake, 3T3-L1 cells were treated with sulfosuccinimidyl oleate, a CD36-specific inhibitor. sulfosuccinimidyl oleate-treated cells showed a significant decrease in both lycopene and lutein uptake as compared to control cells. Their uptake was also decreased by partial inhibition of CD36 expression using siRNA, whereas the overexpression of CD36 in Cos-1 cells increased their uptake. Finally, the effect of CD36 on carotenoid uptake was confirmed ex vivo in cultures of adipose tissue explants from CD36(-/-) mice, which exhibited reduced carotenoid uptake as compared to wild-type mice explants. CONCLUSION: For the first time, we report the involvement of a transporter, CD36, in carotenoid uptake by adipocytes and adipose tissue.

ATP-binding cassette transporter A1 is significantly involved in the intestinal absorption of alpha- and gamma-tocopherol but not in that of retinyl palmitate in mice.

BACKGROUND: It has long been assumed that newly absorbed vitamin A and E enter the body only via enterocyte-produced chylomicrons. However, recent results in cell cultures have shown that a fraction of alpha-tocopherol is secreted with intestinal HDL. OBJECTIVES: The aims of this study were to identify this transporter and to assess whether it is significantly implicated in the in vivo intestinal absorption of the 2 main dietary forms of vitamin E (ie, alpha- and gamma-tocopherol) and in that of retinyl palmitate (vitamin A). DESIGN: Having performed preliminary experiments in the Caco-2 cell model, we compared fasting and postprandial plasma concentrations of vitamins A and E in mice deficient in ATP-binding cassette A1 (ABCA1) transporter and in wild-type mice. RESULTS: A substantial efflux of alpha- and gamma-tocopherol, but not of retinyl esters, was induced by the presence of apolipoprotein A-I at the basolateral side of Caco-2 monolayers. The efflux of alpha- and gamma-tocopherol was also impaired by glyburide and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The postprandial response of plasma gamma-tocopherol was 4-fold lower in ABCA1(-/-) mice (P = 0.025) than in wild-type mice, whereas no significant difference was observed for retinyl esters. Fasting plasma alpha-tocopherol, but not vitamin A, concentrations were lower in mice bearing the genetic deletion. CONCLUSIONS: ABCA1 is the transporter responsible for the in vivo secretion of alpha- and gamma-tocopherol with intestinal HDL, and this pathway is significantly implicated in the intestinal absorption and plasma status of vitamin E but not of vitamin A.

Human fasting plasma concentrations of vitamin E and carotenoids, and their association with genetic variants in apo C-III, cholesteryl ester transfer protein, hepatic lipase, intestinal fatty acid binding protein and microsomal triacylglycerol transfer protein.

Plasma concentrations of vitamin E and carotenoids are governed by several factors, including genetic factors. Single nucleotide polymorphisms (SNP) in some genes involved in lipid metabolism have recently been associated with fasting plasma concentrations of these fat-soluble micronutrients. To further investigate the role of genetic factors that modulate the plasma concentrations of these micronutrients, we assessed whether SNP in five candidate genes (apo C-III, CETP, hepatic lipase, I-FABP and MTP) were associated with the plasma concentrations of these micronutrients. Fasting plasma vitamin E and carotenoid concentrations were measured in 129 French Caucasian subjects (forty-eight males and eighty-one females). Candidate SNP were genotyped by PCR amplification followed by restriction fragment length polymorphisms. Plasma gamma-tocopherol, alpha-carotene and beta-carotene concentrations were significantly different (P < 0.05) in subjects who carried different SNP variants in hepatic lipase. Plasma alpha-tocopherol concentrations were significantly different in subjects who had different SNP variants in apo C-III and cholesteryl ester transfer protein (CETP). Plasma lycopene concentrations were significantly different (P < 0.05) in women who had different SNP variants in intestinal fatty acid binding protein (I-FABP). Finally, there was no effect of SNP variants in microsomal TAG transfer protein upon the plasma concentrations of these micronutrients. Most of the observed differences remained significant after the plasma micronutrients were adjusted for plasma TAG and cholesterol. These results suggest that apo C-III, CETP and hepatic lipase play a role in determining the plasma concentrations of tocopherols while hepatic lipase and I-FABP may modulate plasma concentrations of carotenoids.

Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick C1-like 1.

Cholesterol membrane transporters scavenger receptor class B type I (SR-BI) and (cluster determinant 36) are involved in intestinal uptake of lutein and beta-carotene, 2 of the 3 main carotenoids of the human diet. The aim of this work was therefore to determine whether SR-BI and NPC1L1 (Niemann-Pick C1-like 1), another cholesterol transporter, are implicated in absorption of lycopene, the 3rd main carotenoid of the human diet. Anti-human SR-BI antibody and block lipid transport 1 (BLT1) (a chemical inhibitor of lipid transport by SR-BI) impaired up to 60% (all-E) and (5Z)-lycopene uptake (P < 0.05) by Caco-2 cell monolayers, which were used as a model of human intestinal epithelium. The involvement of SR-BI in lycopene absorption in vivo was then verified by comparing plasma lycopene concentrations in wild-type and SR-BI transgenic mice that were fed a diet enriched with 0.25 g/kg (all-E)-lycopene for 1 mo. Plasma lycopene concentrations were approximately 10-fold higher (P < 0.001) in mice overexpressing SR-BI in the intestine than in wild-type mice, confirming the involvement of SR-BI in lycopene absorption. Further experiments showed that (all-E)-lycopene did not affect SR-BI mRNA levels in Caco-2 cells or mouse intestine. In contrast to SR-BI, neither anti-human NPC1L1 antibody nor ezetimibe, used as inhibitors of lycopene uptake via NPC1L1, significantly impaired (all-E) or (5Z)-lycopene uptake by Caco-2 monolayers. Thus, the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by NPC1L1.

Human plasma levels of vitamin E and carotenoids are associated with genetic polymorphisms in genes involved in lipid metabolism.

Vitamin E and carotenoids are fat-soluble micronutrients carried by plasma lipoproteins. Their plasma concentrations are governed by several factors, some of which are genetic, but data on these genetic factors remain scarce. We hypothesized that genes involved in lipid metabolism, i.e. the genes implicated in intestinal uptake, intracellular trafficking, and the lipoprotein distribution of lipids, play a role in the plasma concentrations of these micronutrients. To verify this hypothesis, we assessed whether the plasma status of vitamin E and carotenoids is related to genes involved in lipid metabolism. Fasting plasma vitamin E (alpha- and gamma-tocopherol) and carotenoid (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, and zeaxanthin) concentrations were measured in 48 males and 80 females. The following genes were genotyped [single nucleotide polymorphisms (SNP)]: apolipoprotein (apo) A-IV, apo B, apo E, lipoprotein lipase, and scavenger-receptor class B type I (SR-BI). Plasma alpha-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV, apo E, and SR-BI. Plasma gamma-tocopherol concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and SR-BI. Alpha-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Beta-carotene concentrations were different (P < 0.05) in subjects bearing different SNP in apo B and SR-BI. Lycopene concentrations were different (P < 0.05) in subjects bearing different SNP in apo A-IV and apo B. Beta-cryptoxanthin concentrations were different (P < 0.05) in subjects bearing different SNP in SR-BI. Plasma lutein and zeaxanthin concentrations did not differ in subjects bearing different SNP. Most of the differences remained significant after the plasma micronutrients were adjusted for plasma triglycerides and cholesterol. These results suggest that genes involved in lipid metabolism influence the plasma concentrations of these fat-soluble micronutrients.

Pancreatic lipase and pancreatic lipase-related protein 2, but not pancreatic lipase-related protein 1, hydrolyze retinyl palmitate in physiological conditions.

The major sources of vitamin A in the human diet are retinyl esters (mainly retinyl palmitate) and provitamin A carotenoids. It has been shown that classical pancreatic lipase (PL) is involved in the luminal hydrolysis of retinyl palmitate (RP), but it is not known whether pancreatic lipase-related proteins 1 (PLRP1) and 2 (PLRP2), two other lipases recovered in the human pancreatic juice, are also involved. The aim of this study was to assess whether RP acts a substrate for these lipase-related proteins. Pure horse PL, horse PLRP2 and dog PLRP1 were incubated with RP solubilized in its physiological vehicles, i.e., triglyceride-rich lipid droplets, mixed micelles and vesicles. High performance liquid chromatography (HPLC) was used to assess RP hydrolysis by the free retinol released in the incubation medium. Incubation of RP-containing emulsions with horse PL and colipase resulted in RP hydrolysis (0.051+/-0.01 micromol/min/mg). This hydrolysis was abolished when colipase was not added to the medium. PLRP2 and PLRP1 were unable to hydrolyze RP solubilized in emulsions, regardless of whether colipase was added to the medium. PL hydrolyzed RP solubilized in mixed micelles as well (0.074+/-0.014 micromol/min/mg). Again, this hydrolysis was abolished in the absence of colipase. PLRP2 hydrolyzed RP solubilized in micelles but less efficiently than PL (0.023+/-0.005 micromol/min/mg). Colipase had no effect on this hydrolysis. PLRP1 was unable to hydrolyze RP solubilized in micelles, regardless of whether colipase was present or absent. Both PL and PLRP2 hydrolyzed RP solubilized in a vesicle rich-solution, and a synergic phenomenon between the two lipases was enlighten. Taken together, these results show that (1) PL hydrolyzes RP whether RP is solubilized in emulsions or in mixed micelles, (2) PLRP2 hydrolyzes RP only when RP is solubilized in mixed micelles, and (3) PLRP1 is unable to hydrolyze RP regardless of whether RP is solubilized in emulsions or in mixed micelles.