The influenza virus-host interaction is a classic arms race. The recurrent and evolving nature of the influenza virus family allows a single host to be infected several times. Locked in co-evolution, recurrent influenza virus infection elicits continual refinement of the host immune system. Here we give historical context of circulating influenza viruses to understand how the individual immune history is mirrored by the history of influenza virus circulation. Original Antigenic Sin was first proposed as the negative influence of the host’s first influenza virus infection on the next and Imprinting modernizes Antigenic Sin incorporating both positive and negative outcomes. Building on imprinting, we refer to preimmunity as the continual refinement of the host immune system with each influenza virus infection. We discuss imprinting and the interplay of influenza virus homology, vaccination, and host age establishing preimmunity. We outline host signatures and outcomes of tandem infection according to the sequence of virus and classify these relationships as monosubtypic homologous, monosubtypic heterologous, heterosubtypic, or heterotypic sequential infections. Finally, the preimmunity knowledge gaps are highlighted for future investigation. Understanding the effects of antigenic variable recurrent influenza virus infection on immune refinement will advance vaccination strategies, as well as pandemic preparedness.

Influenza virus imprinting is now understood to significantly influence the immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year and subsequently build a complex influenza virus immune history. Despite this knowledge, little is known about how the imprinting strain influences vaccine responses. To investigate the immune responses of the imprinted host to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60-day recovery period to build immune memory, ferrets were immunized and then challenged on Day 123. Antibody specificity and recall were investigated throughout the time course. At challenge, the imprinted vaccinated ferrets did not experience significant disease, while naïve-vaccinated ferrets had significant weight loss. Haemagglutination inhibition assays showed that imprinted ferrets had a more robust antibody response post vaccination and increased virus neutralization activity. Imprinted-vaccinated animals had increased virus-specific IgG antibodies compared to the other experimental groups, suggesting B-cell maturity and plasticity at vaccination. These results should be considered when designing the next generation of influenza vaccines.

Background Inadequate pain control after median sternotomy leads to reduced mobilization, increased respiratory complications, and longer hospital stays. Typically, postoperative pain is controlled by opioid analgesics that may have several adverse effects. Parasternal intercostal block (PSB) has emerged as part of a multimodal strategy to control pain after median sternotomy. However, the effectiveness of this intervention on postoperative pain control and analgesic use has not been fully established. Methods and Results We conducted a meta‐analysis to assess the effect of PSB on postoperative pain and analgesic use in adult cardiac surgery patients undergoing median sternotomy. PubMed, Embase, Google Scholar, and the Cochrane database were searched with the following search strategy: ([postoperative pain] or [pain relief] OR [analgesics] or [analgesia] or [nerve block] or [regional block] or [local block] or [regional anesthesia] or [local anesthetic] or [parasternal block] and [sternotomy]) and (humans [filter]). Inclusion criteria were: patients who underwent cardiac surgery via median sternotomy, age >18 and parasternal block (continuous and single dose). Exclusion criteria were: noncardiac surgery, nonparasternal nerve blocks, and the use of NSAIDS in parasternal block. Quality assessment was performed by three independent reviewers via the Cochrane risk of bias assessment tool. Of 1165 total citations, 18 were found to be relevant. Of these 18 citations, 7 citations (N = 2223 patients) reported postoperative pain scores in an extractable format and 11 citations (N = 2155 patients) reported postoperative opioid use in an extractable format. For postoperative opioid use, morphine equivalent doses were calculated for all studies and postoperative pain scores were standardized to a 10‐point visual analog scale for comparison between studies; both these were reported as total opioid use or cumulative score ranging from 24 to 72 h postoperative. All data analyses were run using a random effects model, using a restricted maximum likelihood estimator, to obtain summary standardized mean differences with 95% confidence interval (CI's). For studies which only reported median and interquatile range (IQR), the median was standard deviation was estimated by IQR/1.35. Following median sternotomy both postoperative pain (SMD [95% CI] −0.49 [−0.92 to −0.06]) and postoperative morphine equivalent use (SMD [95% CI] −1.68 [−3.11 to −0.25]) were significantly less in the PSB group. Conclusion Our meta‐analysis suggests that parasternal nerve block significantly reduces postoperative pain and opioid use.

Background: Inadequate analgesia following cardiac surgery increases postoperative complications. Opioid-based analgesia is associated with side effects that may compromise postoperative recovery. Regional anesthetic techniques provide an alternative thereby reducing opioid requirements and potentially enhancing postoperative recovery. The erector spinae plane block has been used in multiple surgical procedures including sternotomy for cardiac surgery. We, therefore, aimed to characterize the impact of this block on post-sternotomy pain and recovery in cardiac surgery patients. Methods:We conducted an electronic search for studies reporting on the use of the erector spinae plane block in adult cardiac surgery via midline sternotomy. Randomized controlled trials, cohort studies, and case-control studies were considered for inclusion. Outcomes of interest included postoperative pain, timeto-extubation, and intensive care unit length of stay.Results: In total, 498 citations were identified and five were included in the metaanalysis. The erector spinae plane block did not significantly reduce self-reported postoperative pain scores at 4 h (−2.04; 95% confidence interval [CI] −8.15 to 4.07; p = .29) or 12 h (−0.27; 95% CI −2.48 to 1.94; p = .65) postextubation, intraoperative opioid requirements (−3.07; 95% CI −6.25 to 0.11; p = .05], time-to-extubation (−1.17; 95% CI −2.81 to 0.46; p = .12), or intensive care unit (ICU) length of stay (−4.51; 95% CI −14.23 to 5.22; p = .24).Conclusions: Erector spinae plane block was not associated with significant reduction in postoperative pain, intraoperative opioid requirements, time-toextubation, and ICU length of stay in patients undergoing cardiac surgery. The paucity of large randomized controlled trials and the high heterogeneity among studies suggest that further studies are required to assess its effectiveness in cardiac surgery patients.

Objective: The objective of this scoping review is to describe the postoperative outcomes and complications of patients with bicuspid aortic valve (BAV) treated with sutureless or rapid-deployment prosthesis.Background: The use of sutureless and rapid-deployment prostheses is generally avoided in patients with BAV due to anatomical concerns and the elevated risk of para-prosthetic leaks. Multiple studies have reported the use of these prostheses into patients with BAV with varying degrees of success. The focus of this review is to consolidate the current available evidence on this topic.Methods: A scoping review was conducted using a comprehensive search strategy in multiple databases (Medline, Embase, Cochrane Central Register of Controlled Clinical Trials) for relevant articles. All abstracts and full texts were screened by two independent reviewers according to predefined inclusion and exclusion criteria.Thirteen articles, including case reports and case series were ultimately included for analysis.Results: Of 1052 total citations, 44 underwent full text review and 13 (4 case reports, 6 retrospective analyses, and 3 prospective analyses) were included in the scoping review. Across all 13 studies, a total of 314 patients with BAV were used for data analysis. In sutureless and rapid-deployment prostheses, the mean postoperative aortic valvular gradients were less than 15 mmHg in all studies with mean postoperative aortic valvular areas all greater than 1.3 cm. 2 There were 186 total complications for an overall complication rate of 59%. Individual complications included new onset atrial fibrillation (n = 65), required pacemaker insertion (n = 24), intraprosthetic aortic regurgitation (n = 20), new onset atrioventricular block (n = 18), and new onset paravalvular leakage (n = 10).Conclusions: The use of sutureless and rapid deployment prostheses in patients with BAV showed comparable intraoperative and implantation success rates to patients without BAV. Postoperative complications from using these prostheses in patients with BAV included new onset atrial fibrillation, intraprosthetic aortic regurgitation, new onset atrioventricular block, and required pacemaker insertion. Various