"Minimally symptomatic" congenital cytomegalovirus infection: latest data and emerging concepts.

PURPOSE OF REVIEW: Universal and targeted screening of newborns for congenital cytomegalovirus (CMV) infection is increasing globally. Questions remain concerning the management of infants who have been identified with congenital CMV infection, especially those with "minimally symptomatic" or clinically inapparent infection. Our objective is to discuss current management of CMV-infected neonates with a focus on less affected infants with or without sensorineural hearing loss (SNHL). RECENT FINDINGS: Valganciclovir is being prescribed increasingly in neonates with congenital CMV infection for improvement in hearing outcomes through 2 years of age. Treatment initiated in the first month of age is recommended for clinically apparent disease. A recent study showed hearing improvement at 18-22 months of age when therapy was initiated at age 1-3 months in infants with clinically inapparent CMV infection and isolated SNHL. SUMMARY: Antiviral therapy with either ganciclovir or valganciclovir has shown moderate benefit in prevention of hearing deterioration among infants with clinically apparent CMV infection or isolated SNHL. Sustainability of benefit beyond 2 years of age remains unknown. At present, infants with clinically inapparent CMV infection (normal complete evaluation including hearing) should not receive antiviral therapy. All CMV-infected infants require close audiological and neurodevelopmental follow-up.

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Pediatric Myocarditis Protocol: An Algorithm for Early Identification and Management with Retrospective Analysis for Validation.

Myocarditis is an inflammatory disease of the myocardium with numerous different etiologies, the vast majority of which are infectious in origin. Patients afflicted with myocarditis can have variable presentations from flu-like symptoms to cardiogenic shock and sudden death, thus making the diagnosis difficult. The purpose of this study is the development of an algorithm for early identification and management of myocarditis based on a review of the published data and available literature. To validate the efficacy of this algorithm, a retrospective chart review of all the patient's presenting symptoms and diagnostic workup, treatment, and clinical progression was performed and applied to the algorithm to investigate whether they could be diagnosed at the time of presentation. Retrospective chart review was performed and all the patient's diagnosed with myocarditis between the years 2009 and 2017 were included in the study. 12 patients were identified on chart review and the algorithm was found to be 100% accurate at identifying all myocarditis patients at presentation by using the symptom identification.

Pre-partying Amongst Students in the UK: Measuring Motivations and Consumption Levels Across Different Educational Contexts.

We sought to explore the motivations for pre-partying amongst UK student drinkers who reported pre-partying at least once per month. Two distinct educational settings were included: colleges, where the majority of students are below the legal age for drinking, and university, where all students would be legally allowed to drink. A cross-sectional correlational design was adopted. Ninety-four college (16-18 years) and 138 university students (18-28 years) from the UK completed an online survey, of whom 54.7% and 86.9% reported pre-partying at least once per month, respectively. Alcohol use was measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) and pre-partying motivations were assessed using the Pre-partying Motivations Inventory (PMI). Frequency of pre-partying behavior and the number of units consumed was also recorded. Hierarchical regression analyses showed that, for college students, AUDIT-C positively predicted pre-partying frequency, while gender and AUDIT-C positively predicted the units of alcohol consumed but Barriers to Consumption (BC) negatively predicted units consumed. Among university students AUDIT-C and Interpersonal Enhancement predicted pre-partying frequency, and AUDIT-C predicted the amount of pre-partying units consumed. Different motives for pre-partying motives were identified across two distinct educational settings. The finding that BC negatively correlated with the amount of alcohol consumed amongst younger college students requires further study, as it contradicts previous work in this area, but is consistent with findings that availability predicts alcohol intake. Understanding differences in drinking behavior between age groups is a key finding, which will allow future research to track developmental influences on the effectiveness of interventions.

Two Infants with Presumed Congenital Zika Syndrome, Brownsville, Texas, USA, 2016-2017.

Since 2007, Zika virus has spread through the Pacific Islands and the Americas. Beginning in 2016, women in Brownsville, Texas, USA, were identified as possibly being exposed to Zika virus during pregnancy. We identified 18 pregnant women during 2016-2017 who had supportive serologic or molecular test results indicating Zika virus or flavivirus infection. Two infants were evaluated for congenital Zika syndrome after identification of prenatal microcephaly. Despite standard of care testing of mothers and neonates, comparative results were unreliable for mothers and infants, which highlights the need for clinical and epidemiologic evidence for an accurate diagnosis. A high index of suspicion for congenital Zika syndrome for at-risk populations is useful because of current limitations of testing.

Violence and Disposability at the Intersection of Twin Pandemics.

COVID-19 and anti-Black violence represent interlocking pandemics animated by necropolitics, the power to determine who lives and who dies. By expanding our understanding of violence to include its structural and cultural forms alongside direct bodily harm, we must also expand our commitment to end violence. Labor educators, organizers, and workers are uniquely positioned to articulate this more expansive definition and advocate for the eradication of violence in all its forms.

Implementation Experience With Meningococcal Serogroup B Vaccines in the United States: Impact of a Nonroutine Recommendation.

BACKGROUND: Meningococcal serogroup B (MenB) is the leading cause of invasive meningococcal disease among US adolescents and young adults, accounting for 62% of cases in 16-23-year-olds in 2018. Since 2015, the Advisory Committee on Immunization Practices (ACIP) has recommended vaccination of healthy adolescents against MenB based on shared clinical decision-making (previously called "Category B" or individual clinical decision-making). However, MenB vaccine coverage and series completion rates remain low. Herein we examine implementation experience of adolescent MenB vaccination in the United States under this nonroutine ACIP recommendation. METHODS: PubMed was searched for English-language articles published after 2015 examining MenB vaccination implementation in the United States. Studies reporting MenB vaccination awareness, coverage, knowledge of recommendations and implementation barriers or access disparities were included. RESULTS: Identified studies provided evidence that ACIP's MenB vaccination recommendation is poorly understood and prone to misinterpretation by US healthcare providers. Parental awareness of MenB vaccines is low, and racial and socioeconomic disparities exist regarding vaccine receipt. Parents rely on providers to learn about MenB disease risk and benefits of vaccination, with provider recommendations carrying substantial weight in vaccination decisions. CONCLUSIONS: Five years of evidence regarding the MenB vaccination implementation experience suggest that the nonstandard recommendation for MenB vaccines is partly responsible for low vaccine coverage. Further, inconsistent implementation of ACIP recommendations could be limiting access to MenB vaccines. Providers need additional support and guidance to implement the shared clinical decision-making recommendation, in turn ensuring equitable access for vaccine-eligible adolescents to enable comprehensive protection against meningococcal disease.

Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients' bone marrow.

T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3-∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p < 0.01), (2) be genetically engineered to express CYP27B1 gene, and (3) infiltrate the BM and reside in close proximity to pre-injected autologous AML blasts of engrafted immunodeficiency mice. Altogether, these results provide a rationale for further studies of the therapeutic use of TILs in AML.

The Interpersonal Transaction Scales-8 (ITS-8): A Circumplex-Based, Behaviorally Anchored Instrument Based on the CLOIT-R.

Using the Checklist of Interpersonal Transactions-Revised (CLOIT-R; Kiesler, 2004) as a basis, a new behaviorally anchored instrument was developed with a graded-response scale, simplified item wording, substantially fewer items, and improved consistency with the interpersonal circumplex. In a community sample (Study 1), the graded response format with simplified items showed improved octant-scale reliabilities, as well as circular structure and convergent validity comparable to the CLOIT-R. Items that performed consistently across community and undergraduate samples (Study 2) were then selected to produce an inventory with half as many items as the CLOIT-R, but with good octant-scale reliabilities and excellent circular structure. Finally, in a therapy context (Study 3), the new inventory showed excellent reliability and validity for ratings of both clients and therapists. This 48-item inventory, the Interpersonal Transaction Scales-8 (ITS-8), may be used for both self- and other-ratings in everyday interactions, as well as for observer ratings of therapeutic interactions.

Hybrid dysgenesis in Drosophila virilis results in clusters of mitotic recombination and loss-of-heterozygosity but leaves meiotic recombination unaltered.

BACKGROUND: Transposable elements (TEs) are endogenous mutagens and their harmful effects are especially evident in syndromes of hybrid dysgenesis. In Drosophila virilis, hybrid dysgenesis is a syndrome of incomplete gonadal atrophy that occurs when males with multiple active TE families fertilize females that lack active copies of the same families. This has been demonstrated to cause the transposition of paternally inherited TE families, with gonadal atrophy driven by the death of germline stem cells. Because there are abundant, active TEs in the male inducer genome, that are not present in the female reactive genome, the D. virilis syndrome serves as an excellent model for understanding the effects of hybridization between individuals with asymmetric TE profiles. RESULTS: Using the D. virilis syndrome of hybrid dysgenesis as a model, we sought to determine how the landscape of germline recombination is affected by parental TE asymmetry. Using a genotyping-by-sequencing approach, we generated a high-resolution genetic map of D. virilis and show that recombination rate and TE density are negatively correlated in this species. We then contrast recombination events in the germline of dysgenic versus non-dysgenic F1 females to show that the landscape of meiotic recombination is hardly perturbed during hybrid dysgenesis. In contrast, hybrid dysgenesis in the female germline increases transmission of chromosomes with mitotic recombination. Using a de novo PacBio assembly of the D. virilis inducer genome we show that clusters of mitotic recombination events in dysgenic females are associated with genomic regions with transposons implicated in hybrid dysgenesis. CONCLUSIONS: Overall, we conclude that increased mitotic recombination is likely the result of early TE activation in dysgenic progeny, but a stable landscape of meiotic recombination indicates that either transposition is ameliorated in the adult female germline or that regulation of meiotic recombination is robust to ongoing transposition. These results indicate that the effects of parental TE asymmetry on recombination are likely sensitive to the timing of transposition.

Clinical application of voriconazole concentrations in the treatment of invasive aspergillosis.

OBJECTIVE: To review the current literature to determine the clinical application of therapeutic drug monitoring of voriconazole in the treatment of invasive aspergillosis (IA). DATA SOURCE: A MEDLINE search (1966-June 2008) was performed using the search terms voriconazole, aspergillosis, levels, monitoring, and serum concentration. STUDY SELECTION AND DATA EXTRACTION: All pertinent English-language literature on voriconazole use in adults was included for evaluation. DATA SYNTHESIS: IA is a serious fungal infection with a mortality rate of nearly 100% without adequate treatment; current therapeutic options are limited. A clinical trial comparing amphotericin B deoxycholate with voriconazole in treatment of IA found voriconazole to be superior. The use of voriconazole, however, is complicated due to its saturable metabolism, nonlinear kinetic profile, and drug interactions, which result in considerable interpatient variability in concentrations. Therefore, therapeutic monitoring of voriconazole trough concentrations may lead to improved patient outcomes. A recent prospective study on the use of voriconazole for treatment of invasive mycoses demonstrated that 46% of the patients had a lack of response when trough plasma concentrations were less than or equal to 1 microg/mL, compared with 12% of patients with trough concentrations greater than 1 microg/mL (p = 0.02). All patients with low trough concentrations who did not respond to voriconazole improved upon dose escalation. The upper limit of a therapeutic range is based on the presence of adverse events. The most common adverse effects associated with voriconazole are visual disturbances (21%) and elevations in liver transaminase levels (12.4%). Current literature suggests that a greater incidence of adverse effects may be associated with trough concentrations greater than 6 microg/mL. CONCLUSIONS: A standardized therapeutic range for voriconazole has not been defined. Most available studies recommend trough concentrations of approximately 1-6 microg/mL. Prospective, randomized trials are needed to confirm the correlation between plasma voriconazole concentrations and clinical outcomes.

Murine Typhus in South Texas Children: An 18-year Review.

BACKGROUND: Murine typhus is a zoonotic infection caused by Rickettsia typhi that remains endemic in South Texas. In 2003, only 9 Texas counties reported murine typhus compared with 41 counties in 2013. METHODS: A retrospective study of children discharged with a confirmed diagnosis of murine typhus from Driscoll Children's Hospital between January 1998 and September 2016. RESULTS: Two hundred thirteen children (113 female) 3 months through 19 years of age (mean, 11.2 ± 4.5 years) were identified. Cases occurred throughout the year. Children were admitted after a mean of 7.7 ± 5.3 days of fever. The most common symptoms were fever (100%), poor appetite (71.9%), malaise/fatigue (69.0%) and headache (67.6%). The most common laboratory abnormalities were elevated C-reactive protein, hypoalbuminemia, elevated erythrocyte sedimentation rate, elevated transaminases and elevated band count with normal total white blood cell count. Children defervesced in a mean of 31.87 ± 21.36 hours after initiation of doxycycline. Hospitalization lasted for a mean of 2.7 ± 1.8 days when children were administered doxycycline within 24 hours of admission compared with, 4.1 ± 1.8 days, P ≤ 0.0001 when started later. Eleven patients (5.1%) were admitted to the pediatric intensive care unit and were older, P = 0.0009. No children died. CONCLUSIONS: Murine typhus is endemic in South Texas. Children who were treated earlier with doxycycline had a shorter hospitalization than were those who began therapy later. Recognition of murine typhus is important to prevent delay in treatment and development of complications.

Influenza-Associated Acute Necrotizing Encephalopathy in Siblings.

Encephalopathy is an important complication associated with influenza, most frequently observed in young children, with a wide range of severity. The most severe category of influenza-associated encephalopathy (IAE) is acute necrotizing encephalopathy (ANE), characterized by high frequency of neurologic sequelae and fatal outcomes. We report two young siblings who developed fever and seizures with altered mental status. Influenza A(H1N1)pdm09 virus infection was identified in upper respiratory tract specimens from both patients, and neuroimaging revealed bilateral inflammatory lesions, consistent with acute necrotizing encephalopathy. Neither child had received influenza vaccination. Both children progressed to critical illness and required invasive mechanical ventilation. In addition to critical care management, both patients received high-dose corticosteroids, mannitol, anticonvulsants, and antiviral treatment of influenza. The older child recovered fully and was discharged 2 weeks after illness onset, but the younger sibling developed severe brainstem edema and cerebellar tonsillar herniation, and died on illness day 11. Both children tested positive for Ran Binding Protein 2 (RANBP2) gene mutations. RANBP2 is a genetic polymorphism associated with recurrent episodes of necrotizing encephalitis with respiratory viral infections. Annual influenza vaccination is especially important for ANE survivors, with or without RANBP2 mutations, their household contacts, and caregivers. During influenza season, close monitoring of any child with a history of neurological complications associated with respiratory illness is indicated, with prompt initiation of antiviral treatment with onset of acute respiratory illness, and influenza testing performed by molecular assay.