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Background Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. Methods This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3–17 years old who were 3–35 months post-allogeneic HCT, with each formulation administered twice, 28–42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28–42 days following each dose, and 138–222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3–5 and 6–35 months post-HCT, respectively. Results During 3 influenza seasons (2016–2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14–4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60–6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01–3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59–1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68–2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56–2.03]). Conclusions Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. Clinical Trials Registration NCT02860039. [ABSTRACT FROM AUTHOR]

Background: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS‐CoV‐2+ donors. Methods: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS‐CoV‐2 nucleic acid test‐positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform. Results: The first donor was a 3‐year‐old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS‐CoV‐2 infection before organ procurement. The second donor was a 16‐month‐old boy with cardiopulmonary arrest of unknown etiology. Three NAT tests (2 NP swab/1 BAL) prior to procurement failed to detect SARS‐CoV‐2. The diagnosis was made when the medical examiner repeated 2 NP swab NATs and an archive plasma NAT, all positive for SARS‐CoV‐2. Both 2‐year‐old recipients continue to do well 8 months post‐transplant, with excellent graft function and no evidence of SARS‐CoV‐2 transmission. Conclusions: This is the first report to describe successful pediatric liver transplantation from SARS‐CoV‐2+ donors. These data reinforce the adult transplant experience and support the judicious use of SARS‐CoV‐2+ donors for liver transplantation in children. With SARS‐CoV‐2 becoming endemic, the concern for donor‐derived viral transmission must now be weighed against the realized benefit of life‐saving transplantation in the pediatric population as we continue to work toward donor pool maximization. [ABSTRACT FROM AUTHOR]

As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being. [ABSTRACT FROM AUTHOR]

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy. [ABSTRACT FROM AUTHOR]

We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19. [ABSTRACT FROM AUTHOR]

Poxviruses subvert the host immune response by producing immunomodulatory proteins, including a complement regulatory protein. Ectromelia virus provides a mouse model for smallpox where the virus and the host's immune response have co-evolved. Using this model, our study investigated the role of the complement system during a poxvirus infection. By multiple inoculation routes, ectromelia virus caused increased mortality by 7 to 10 days post-infection in C57BL/6 mice that lack C3, the central component of the complement cascade. In C3-/- mice, ectromelia virus disseminated earlier to target organs and generated higher peak titers compared to the congenic controls. Also, increased hepatic inflammation and necrosis correlated with these higher tissue titers and likely contributed to the morbidity in the C3-/- mice. In vitro, the complement system in naïve C57BL/6 mouse sera neutralized ectromelia virus, primarily through the recognition of the virion by natural antibody and activation of the classical and alternative pathways. Sera deficient in classical or alternative pathway components or antibody had reduced ability to neutralize viral particles, which likely contributed to increased viral dissemination and disease severity in vivo. The increased mortality of C4-/- or Factor B-/- mice also indicates that these two pathways of complement activation are required for survival. In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection. [ABSTRACT FROM AUTHOR]

Background Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR is limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR. Methods A retrospective cohort study of patients <22 yr of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2014 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). Primary outcome was CMV DNAemia (plasma level ≥ 1,000 IU/mL). Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots. Results Among 465 SOTR, 57 (12%) had CMV DNAemia ≥ 1,000 IU/mL; this included 9/52 (17%) lung, 22/155 (14%) liver, 16/125 (13%) heart, 1/9 (11%) multi-organ, and 9/124 (7%) kidney recipients. 6 (10%) SOTR had early-onset CMV reactivation while on antiviral prophylaxis. Post-prophylaxis, 48 (85%) SOTR had CMV reactivation and 3 (5%) had primary infection. Median time to DNAemia > 1,000 IU/mL was 366 days post-transplant for lung, 115 for liver, 185 for heart, and 290 for kidney (P = 0.04), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R- for heart, liver, kidney and D+ and/or R+ for lung) was associated with CMV DNAemia (P < 0.01, Figure 2). DNAemia was not associated with age at transplantation, type of organ, or induction immunosuppression. There was no difference in survival during the study follow-up period (1 – 5 years) for SOTR with vs. without DNAemia. Overall, 18/465 (4%) SOTR had CMV disease: 2 (4%) lung, 3 (2%) liver, 5 (4%) heart, 1 (11%) multi-organ, and 7 (6%) kidney recipients. 16 had CMV syndrome and 2 had tissue-invasive disease. Median (range) maximum viral loads were 35,768 IU/mL (3,239–4,807,992) for SOTR with vs. 2,605 IU/mL (1,000–112,000) for SOTR without CMV disease (P < 0.01) Conclusion This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted. Disclosures Flor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support. [ABSTRACT FROM AUTHOR]

Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS is classified as either diarrhea associated, most commonly caused by infection with Escherichia coli O157, or the less common atypical HUS (aHUS), which may be familial or sporadic. Approximately 50% of patients with aHUS have mutations in one of the complement control proteins: factor H, factor I, or membrane cofactor protein (MCP). These proteins regulate complement activation through cofactor activity, the inactivation of C3b by limited proteolytic cleavage, a desirable event in the fluid phase (no target) or on healthy self-tissue (wrong target). Complement activation follows the endothelial cell injury that characterizes HUS. This disease represents a model of what takes place when inappropriate complement activation occurs on self-tissues due to the presence of mutated complement regulatory proteins. Screening for mutations in factor H, factor I, or MCP is expensive and time consuming. One approach is to perform antigenic screening for factor H and factor I deficiency and to look for low levels of MCP (CD46) expression by flow cytometry. Complement regulatory protein deficiency impacts treatment decisions as patients with aHUS have a recurrence rate in renal transplants of ∼50%, whereas those with factor H mutations have an even higher risk (∼80%). By contrast, MCP deficiency can be corrected in part by a renal allograft. However, caution in the use of liverelated donations is needed because of the high rates of incomplete penetrance of the described mutations. [ABSTRACT FROM AUTHOR]

As nursing continues to develop as a professional discipline, it is important for nurses to have a central question to guide their research. Since the 1800s, nursing practice and research have covered a wide scope in cooperation with other disciplines. This wide area of nursing practice and research has led to the proposal that the central question be: How can the well‐being of a person, family, community, or population be improved? The proposed question must remain flexible and open to revision because nurses will continue to adapt to the changing needs of their patients and populations and to their complex and evolving work environments. [ABSTRACT FROM AUTHOR]

The article provides information about the significance of fully innovative training (FIT) for general practice registrars in Leeds, England. It has cited that FIT registrars were positive about the conventional scheme, highlighting relevance to general practice and appropriateness to individual needs as advantages.