A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

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.

Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis.

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients.

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long-term outcomes of CMV DNAemia in pediatric SOTR. We performed a single-center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue-invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High-risk (OR 6.86 [95% CI, 3.6-12.9]) and intermediate-risk (4.36 [2.3-8.2]) CMV status and lung transplantation (4.63 [2.33-9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all-cause mortality, or other organ-specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.

Acute Hepatitis and Adenovirus Infection Among Children - Alabama, October 2021-February 2022.

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.

A new chapter in an evolving pandemic: Successful pediatric liver transplantation with SARS-CoV-2+ donors.

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.

A eulogy for Dr Francisco Miguel Marty Forero.

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.

The central question and the scope of nursing research.

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.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

Ectromelia virus inhibitor of complement enzymes protects intracellular mature virus and infected cells from mouse complement.

Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.

Measures of movement and mobility used in clinical practice and research: a scoping review.

OBJECTIVE: The first objective of this scoping review was to identify all the tools designed to measure movement or mobility in adults. The second objective was to compare the tools to the conceptual definitions of movement and mobility by mapping them to the International Classification of Functioning, Disability and Health (ICF). INTRODUCTION: The concepts of movement and mobility are distinct concepts that are often conflated, and the differences are important to patient care. Movement is a change in the place or position of a part of the body or of the whole body. Mobility is derived from movement and is defined as the ability to move with ease. Researchers and clinicians, including nurses, physiotherapists, and occupational therapists who work with adults and in rehabilitation, need to be confident that they are measuring the outcome of interest. INCLUSION CRITERIA: This scoping review considered studies that included participants who are adults, aged 19 and older, with any level of ability or disability. The concepts of interest were tools that measured movement or mobility relative to the human body. Studies were considered regardless of country of origin, health care setting, or sociocultural setting. METHODS: CINAHL, Health and Psychosocial Instruments, MEDLINE, and Embase were searched in June 2018 and OpenGrey, Dissertation Abstracts International, and Google Scholar were searched in November 2018. The searches were limited to articles in English, and the date range was from the inception of the database to the current date. Data were extracted from the studies using a custom data extraction tool. Once tools were identified for analysis, they were coded using the table format developed by Cieza and colleagues. RESULTS: There were 702 unique tools identified, with 651 of them available to be coded for the ICF. There were 385 ICF codes used when coding the tools. From these codes, the percentage of codes of the defining attributes of movement and mobility that were covered could be calculated, as well as the percentage of tool items that were linked to the antecedents, consequences, or defining attributes of movement or mobility. CONCLUSIONS: Although there are many tools that measure only movement or mobility, there are many that measure a mixture of the defining attributes as well as the antecedents and consequences. The tool name alone should not be considered a guarantee of the concept measured, and tool selection should be done with a critical eye. This study provides a starting point from which clinicians and researchers can find tools that measure the concepts of movement and mobility of interest and importance to their patient population.

Surviving mousepox infection requires the complement system.

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.

Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes.

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.

Movement and Mobility: A Concept Analysis.

This article provides an analysis of the concepts of movement and mobility within the context of the International Classification of Functioning, Disability, and Health (ICF) for patients' functioning, disability, and health. The methodology developed by Walker and Avant was used to clarify definitions, components, and relationships relevant to the 2 concepts and to the elements of the ICF framework. Definitions and the relationship between concepts are key information that clinicians and researchers need to measure the correct concept when they are assessing the effectiveness of interventions in nursing practice. Concept analysis findings are grounded by the notion that movement occurs when the body causes its own displacement and is explained by the basic principles of physics, human anatomy, and physiology. Mobility is then distinct because it is affected by the environment that the individual is in and can be assisted by any type of mobility aid. Mobility does not need to be generated by the individual's muscles but does need to be controlled by the individual who is mobile. An individual's mobility in his or her environment is important to his or her well-being and needs to be understood in relationship to his or her movements.

Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome.

The hemolytic uremic syndrome is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. There are two general types. One occurs in epidemic form and is diarrheal associated (D+HUS). It has a good prognosis. The second is a rare form known as atypical (aHUS), which may be familial or sporadic, and has a poor prognosis. aHUS is increasingly recognized to be a disease of defective complement regulation, particularly cofactor activity. Mutations in membrane cofactor protein (MCP; CD46) that predispose to the development of aHUS were first identified in 2003. MCP is a membrane-bound complement regulator that acts as a cofactor for the factor I-mediated cleavage of C3b and C4b deposited on host cells. More than 20 different mutations in MCP have now been identified in patients with aHUS. Many of these mutants have been functionally characterized and have helped to define the pathogenic mechanisms leading to aHUS development. Over 75% of the reported mutations cause a reduction in MCP expression, due to homozygous, compound heterozygous or heterozygous mutations. This deficiency of MCP leads to inadequate control of complement activation on endothelial cells after an initiating injury. The remaining MCP mutants are expressed, but demonstrate reduced ligand (C3b/C4b) binding capacity and cofactor activity of MCP. MCP mutations in aHUS demonstrate incomplete penetrance, indicating that additional genetic and environmental factors are required to manifest disease. MCP mutants as a cause of aHUS have a favorable clinical outcome in comparison to patients with factor H (CFH) or factor I (IF) mutations. In 90% of the renal transplants performed in patients with MCP-HUS, there has been no recurrence of the primary disease, whilst >50% of factor I or factor H deficient patients have had a prompt recurrence. This highlights the importance of defining and characterizing the underlying genetic defects in patients with aHUS.

Measures of movement and mobility used in clinical practice and research: a scoping review protocol.

REVIEW QUESTION: The first objective of this scoping review is to identify all tools designed to measure movement or mobility in adults. The second objective is to compare the tools to the conceptual definitions of movement and mobility by mapping them against the International Classification of Functioning, Disability and Health (ICF).The specific questions that will be answered for each tool by the mapping are.

Poder interprofissional em cuidados intensivos: reflexão filosófica a partir de perspectivas foucaultianas e críticas / Poder interprofesional en cuidados intensivos: reflexión filosófica a partir de perspectivas foucaultianas y críticas / Interprofessional Power in Acute Care: Philosophical Reflection using Foucauldian and Critical Perspectives

Resumo Objetivo Discutir as relações de poder entre profissionais de saúde em ambientes de cuidado intensivo e sua interferência no processo de construção do conhecimento. Métodos Neste artigo filosófico, exploramos a influência das relações de poder na construção do conhecimento, a partir das perspectivas foucaultiana e crítica de Gramsci e Freire em relação às práticas de enfermagem e cuidados de saúde. Resultados Há quatro fontes de poder organizacional (tomada de decisão, critério, controle de recursos e controle de conhecimento/rede) que atuam em diferentes níveis das organizações de saúde. As unidades de terapia intensiva são um importante segmento do ambiente de saúde, e a complexidade no cotidiano dos profissionais desse setor pode dificultar as relações de poder no processo de construção do conhecimento. Por exemplo, quando profissionais externos à equipe da UTI, que detêm conhecimentos específicos, precisam ser contatados para auxiliar em casos, como durante o processo de doação e transplante de órgãos. Nesta situação, é necessário desconstruir o poder competitivo para construir o poder colaborativo. Conclusão Usando as perspectivas de Freire e Gramsci, argumentamos que a falta de conhecimento contribui para o poder competitivo, que pode ser superado se os indivíduos envolvidos participarem no processo de aprendizagem em direção ao poder colaborativo. Portanto, as estratégias ou ações para lidar com os desequilíbrios de poder interprofissional podem contribuir para a transformação e mudança mútua.

Resumen Objetivo Discutir las relaciones de poder entre profesionales de salud en ambientes de cuidado intensivo y su interferencia en el proceso de construcción del conocimiento. Métodos En este artículo filosófico, exploramos la influencia de las relaciones de poder en la construcción del conocimiento a partir de las perspectivas foucaultianas y la crítica de Gramsci y de Freire en relación con las prácticas de enfermería y los cuidados de salud. Resultados Hay cuatro fuentes de poder organizativo (toma de decisión, criterio, control de recursos y control de conocimiento/red) que actúan en distintos niveles de las organizaciones de salud. Las unidades de cuidados intensivos son un importante sector del ambiente de la salud, y la complejidad en la labor cotidiana de los profesionales de ese sector puede dificultar las relaciones de poder en el proceso de construcción del conocimiento. Por ejemplo, cuando profesionales externos al equipo de la UCI, que tienen conocimientos específicos, tienen que ser contactados para auxiliar en algunos casos, como durante el proceso de donación y trasplante de órganos. En esta situación se hace necesario deconstruir el poder competitivo para construir el poder colaborativo. Conclusión Usando las perspectivas de Freire y de Gramsci, argumentamos que la falta de conocimiento contribuye para el poder competitivo, que se puede superar si los individuos involucrados participan en el proceso de aprendizaje en dirección al poder colaborativo. Por lo tanto, las estrategias o las acciones para hacer frente a los desequilibrios de poder interprofesional pueden contribuir con la transformación y el cambio mutuo.

Abstract Objective To discuss the power relations among health care professionals in acute care settings and its interference in the process of knowledge building. Methods In this philosophical paper, we explored the influence of power relations on knowledge building using a Foucauldian and critical perspective of Gramsci and Freire related to nursing and health care practices. Results There are four sources of organizational power (decision-making, discretion, control of resources, and control of knowledge/network) that act at different levels of healthcare organizations. Intensive care units are an important segment of healthcare setting, and the complexity involved in the daily activities of professionals in this sector can lead to difficult power relations in the process of knowledge building. For instance, when professionals external to the ICU team that hold specific knowledge need to be contacted to help in cases, such as during organ donation and transplantation process. In this situation it is necessary to deconstruct the competitive power in order to build the collaborative power. Conclusion Using Freire's and Gramsci's perspectives we argued that lack of knowledge contributes to competitive power which can be overcome if involved individuals engage in the learning process towards a collaborative power approach. Therefore, strategies or action to address interprofessional power imbalances can contribute mutual transformation and change.