Multisystem Inflammatory Syndrome in Children and Cardiac Involvement: A Quaternary Center Experience.

We prospectively analyzed clinical and laboratory characteristics associated with cardiac involvement and severe presentation in multisystem inflammatory syndrome in children. Of 146 patients, 66 (45.2%) had cardiac dysfunction and 26 (17.8%) had coronary artery abnormalities. Lower serum albumin levels, absolute lymphocyte and platelet counts, and elevated ferritin, fibrinogen, d-dimer and interleukin-6 levels were associated with cardiac dysfunction. Possible treatment complications were identified.

Direct Admission Program Implementation: A Qualitative Analysis of Variation Across Health Systems.

OBJECTIVES: Direct admission (DA) to the hospital has the potential to improve family satisfaction and timeliness of care by bypassing the emergency department. Using the RE-AIM implementation framework, we sought to characterize variation across health systems in the reach, effectiveness, adoption, and implementation of a DA program from the perspectives of parents and multidisciplinary clinicians. METHODS: As part of a stepped-wedge cluster randomized trial to compare the effectiveness of DA to admission through the emergency department, we evaluated DA rates across 69 clinics and 3 health systems and conducted semi-structured interviews with parents and clinicians. We used thematic analysis to identify themes related to the reach, effectiveness, adoption, and implementation of the DA program and applied axial coding to characterize thematic differences across sites. RESULTS: Of 2599 hospitalizations, 171 (6.6%) occurred via DA, with DA rates varying 10-fold across health systems from 0.9% to 9.3%. Through the analysis of 137 interviews, including 84 with clinicians and 53 with parents, we identified similarities across health systems in themes related to perceived program effectiveness and patient and family engagement. Thematic differences across sites in the domains of program implementation and clinician adoption included variation in transfer center efficiency, trust between referring and accepting clinicians, and the culture of change within the health system. CONCLUSIONS: The DA program was adopted variably, highlighting unique challenges and opportunities for implementation in different hospital systems. These findings can inform future quality improvement efforts to improve transitions to the hospital.

Use of Advanced Diagnostics for Timely Identification of Travel-associated Leptospira santarosai Infection in Four Adolescents Through Plasma Microbial Cell-free DNA Sequencing With the Karius Test.

BACKGROUND: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease. METHODS: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period across the United States in 2021 and were clinically reviewed. RESULTS: In our case series, 4 adolescents with recent travel to Central America (Costa Rica, n = 3 and Belize, n = 1) from April to August 2021 were diagnosed with leptospirosis. While a large workup was performed in all cases, mcfDNA testing was the first test to detect L. santarosai as the microbiological diagnosis in all cases. CONCLUSIONS: Results of the Karius Test enabled rapid, noninvasive diagnosis of leptospirosis allowing for targeted therapy. Use of mcfDNA can be utilized for diagnosis of pathogens where conventional testing is challenging or limited. This in turn can enable quick diagnosis for targeted treatment and potentially aid in supporting case definitions of reportable diseases of public health concern.

Multisystem inflammatory syndrome in children associated with COVID-19: from pathophysiology to clinical management and outcomes.

Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome (PIMS), is a new postinfectious illness associated with COVID-19, affecting children after SARS-CoV-2 exposure. The hallmarks of this disorder are hyperinflammation and multisystem involvement, with gastrointestinal, cardiac, mucocutaneous, and hematologic disturbances seen most commonly. Cardiovascular involvement includes cardiogenic shock, ventricular dysfunction, coronary artery abnormalities, and myocarditis. Now entering the fourth year of the pandemic, clinicians have gained some familiarity with the clinical presentation, initial diagnosis, cardiac evaluation, and treatment of MIS-C. This has led to an updated definition from the Centers for Disease Control and Prevention in the USA driven by increased experience and clinical expertise. Furthermore, the available evidence established expert consensus treatment recommendations supporting a combination of immunoglobulin and steroids. However, the pathophysiology of the disorder and answers to what causes this remain under investigation. Fortunately, long-term outcomes continue to look promising, although continued follow-up is still needed. Recently, COVID-19 mRNA vaccination is reported to be associated with reduced risk of MIS-C, while further studies are warranted to understand the impact of COVID-19 vaccines on MIS-C. We review the findings and current literature on MIS-C, including pathophysiology, clinical features, evaluation, management, and medium- to long-term follow-up outcomes.

Update on nonpolio enterovirus and parechovirus infections in neonates and young infants.

PURPOSE OF REVIEW: To review the epidemiology, clinical manifestations, and treatment strategies of nonpolio enterovirus and parechovirus (PeV) infections, and identify research gaps. RECENT FINDINGS: There is currently no approved antiviral agent for enterovirus or PeV infections, although pocapavir may be provided on a compassionate basis. Elucidation of the structure and functional features of enterovirus and PeV may lead to novel therapeutic strategies, including vaccine development. SUMMARY: Nonpolio human enterovirus and PeV are common childhood infections that are most severe among neonates and young infants. Although most infections are asymptomatic, severe disease resulting in substantial morbidity and mortality occurs worldwide and has been associated with local outbreaks. Long-term sequelae are not well understood but have been reported following neonatal infection of the central nervous system. The lack of antiviral treatment and effective vaccines highlight important knowledge gaps. Active surveillance ultimately may inform preventive strategies.

Asymptomatic COVID-19 Reinfection in a Pediatric Patient with Heterotaxy Syndrome.

We report an asymptomatic child with heterotaxy syndrome who had recurrent positive SARS-CoV-2 polymerase chain reaction testing. An aberrant lymphocyte population expressing CD19, CD16, and CD56 was identified; its phenotyping revealing atypical NK cells. This subset's role in protection from severe disease or in reinfection cannot be ascertained.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation.

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing; in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing.

Association of Models of Care for Kawasaki Disease With Utilization and Cardiac Outcomes.

OBJECTIVES: Describe the prevalence of different care models for children with Kawasaki disease (KD) and evaluate utilization and cardiac outcomes by care model. METHODS: Multicenter, retrospective cohort study of children aged 0 to 18 hospitalized with KD in US children's hospitals from 2017 to 2018. We classified hospital model of care via survey: hospitalist primary service with as-needed consultation (Model 1), hospitalist primary service with automatic consultation (Model 2), or subspecialist primary service (Model 3). Additional data sources included administrative data from the Pediatric Health Information System database supplemented by a 6-site chart review. Utilization outcomes included laboratory, medication and imaging usage, length of stay, and readmission rates. We measured the frequency of coronary artery aneurysms (CAAs) in the full cohort and new CAAs within 12 weeks in the 6-site chart review subset. RESULTS: We included 2080 children from 44 children's hospitals; 21 hospitals (48%) identified as Model 1, 19 (43%) as Model 2, and 4 (9%) as Model 3. Model 1 institutions obtained more laboratory tests and had lower overall costs (P < .001), whereas echocardiogram (P < .001) and immune modulator use (P < .001) were more frequent in Model 3. Secondary outcomes, including length of stay, readmission rates, emergency department revisits, CAA frequency, receipt of anticoagulation, and postdischarge CAA development, did not differ among models. CONCLUSIONS: Modest cost and utilization differences exist among different models of care for KD without significant differences in outcomes. Further research is needed to investigate primary service and consultation practices for KD to optimize health care value and outcomes.

Systematic review and meta-analysis of randomized controlled trials on safety and effectiveness of oral anticoagulants for atrial fibrillation in older people.

A meta-analysis of prospective, randomized controlled trials on novel oral anticoagulants (NOACs) versus warfarin, as most commonly used vitamin K antagonists (VKAs), was done to evaluate their effect on stroke risk and bleeding complications in nonvalvular atrial fibrillation (AF) patients. The study aims to evaluate efficacy and safety of NOACs versus warfarin between patients < 75 years and ≥ 75 years old. Prospective, randomized controlled trials (RCTs) comparing NOACs with warfarin with at least 1-year follow-up in nonvalvular AF patients were included. Search was done at MEDLINE, without time and language restriction. "Cochrane risk of bias 2.0 tool" was used to assess risk of bias. In meta-analysis, random effect model was used. Q statistics was used to assess heterogeneity where it was indicated and I2 was used to assess inconsistency across studies. Five studies as RELY, ARISTOTLE, ENGAGE-AF, ROCKET-AF, and J-ROCKET-AF were included. Overall risk of bias was low for trials. Total patient number in meta-analysis was 73,122. Mean age was between 70 and 73 as a whole. Follow-up period was between 499 days and 2.8 years. Analysis of major stroke and systemic embolism was favoring NOACs than warfarin in older patients group period (RR (95% CI) = 0.57 (0.42, 0.76)). Similar trend was seen in younger patient group without statistical significant (RR (95% CI) = 0.74 (0.43, 1.27)). Analysis of major bleeding showed a general statistically significant trend of occurrence of major bleeding in whole group (RR (95% CI) = 0.70 (0.58, 0.86)) with NOACs. In subgroup analysis, it was consistent for both younger and older patients. Older patients have higher stroke risk that leads to more benefit with anticoagulation than younger patients. NOACs have better efficacy profile than warfarin as they decrease stroke more than warfarin, without increasing bleeding risk. Need for real-world data in old population is necessary.

Quality improvement methodology can reduce hospitalisation for abscess management.

BACKGROUND: Abscesses are a common reason for ED visits. While many are drained in the ED, some require drainage in the operating room (OR). We observed that a higher percentage of patients at our institution in Columbus, Ohio, were admitted to the hospital with abscesses for incision and drainage (I&D) in the OR than other institutions, including paediatric institutions. Our aim was to decrease hospitalisations for abscess management. METHODS: A multidisciplinary team convened to decrease hospitalisation for patients with abscesses and completed multiple 'Plan-Do-Study-Act' cycles, including increasing I&Ds performed in the ED. Other interventions included implementation of a clinical pathway, training of procedure technicians (PT), updating the electronic medical record (EMR), credentialing advanced practice nurses in sedation and individual follow-up with providers for admitted patients. Data were analysed using statistical process control charts. Gross average charges were assessed. RESULTS: Admissions for I&D decreased from 26.3% to 13.7%. Abscess drainage in the ED improved from 79.3% to 96.5%. Mean length of stay decreased from 19.5 to 11.5 hours for all patients. Patients sedated increased from 3.3% to 18.2%. The number of repeat I&Ds within 30 days decreased from 4.3% to 1.7%. CONCLUSION: We decreased hospitalisations for abscess I&D by using quality improvement methodology. The most influential intervention was an initiative to increase I&Ds performed in the ED. Additional interventions included expanded training of PTs, implementation of a clinical pathway, updating the EMR, improving interdepartmental communication and increasing sedation providers.

Is heart failure an obstacle to air travel?

Rapid increasing trend in air travel brings necessity of urgent approach to health situations such as heart failure (HF). The prevalence of HF was projected to be more than 8 million patients ≥18 years of age in 2030; Main factors that contribute to physiological changes to cardiovascular system during a flight are changes in cabin pressure, humidity, stress, prolonged mobility. Identifying patients at risk of pre/post and during air travel along with adequate care by physicians and crew would help in better outcomes and comfortable travel for patients with HF.

EVALI versus MIS-C, one more overlapping diagnosis to consider.

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased D-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 polymerase chain reaction and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic. Keywords COVID-19 pandemic, EVALI, MIS-C.

Aortic valve function post-replacement of severe aortic stenosis by transcatheter procedure versus surgery: a systematic review and metanalysis.

Transcatheter aortic valve replacement (TAVR) has shown to reduce mortality compared to surgical aortic valve replacement (sAVR). However, it is unknown which procedure is associated with better post-procedural valvular function. We conducted a meta-analysis of randomized clinical trials that compared TAVR to sAVR for at least 2 years. The primary outcome was post-procedural patient-prosthesis-mismatch (PPM). Secondary outcomes were post-procedural and 2-year: effective orifice area (EOA), paravalvular gradient (PVG) and moderate/severe paravalvular leak (PVL). We identified 6 trials with a total of 7022 participants with severe aortic stenosis. TAVR was associated with 37% (95% CI [0.51-0.78) mean RR reduction of post-procedural PPM, a decrease that was not affected by the surgical risk at inclusion, neither by the transcatheter heart valve system. Postprocedural changes in gradient and EOA were also in favor of TAVR as there was a pooled mean difference decrease of 0.56 (95% CI [0.73-0.38]) in gradient and an increase of 0.47 (95% CI [0.38-0.56]) in EOA. Additionally, self-expandable valves were associated with a higher decrease in gradient than balloon ones (beta = 0.38; 95% CI [0.12-0.64]). However, TAVR was associated with a higher risk of moderate/severe PVL (pooled RR: 9.54, 95% CI [5.53-16.46]). All results were sustainable at 2 years.

Year-Round, Routine Testing of Multiple Body Site Specimens for Human Parechovirus in Young Febrile Infants.

OBJECTIVES: To test our hypothesis that routine year-round testing of specimens from multiple body sites and genotyping of detected virus would describe seasonal changes, increase diagnostic yield, and provide a better definition of clinical manifestations of human parechovirus (PeV-A) infections in young febrile infants. STUDY DESIGN: PeV-A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was incorporated in routine evaluation of infants aged ≤60 days hospitalized at Nationwide Children's Hospital for fever and/or suspected sepsis-like syndrome beginning in July 2013. We reviewed electronic medical records of infants who tested positive for PeV-A between July 2013 and September 2016. Genotyping was performed with specific type 3 RT-PCR and sequencing. RESULTS: Of 1475 infants evaluated, 130 (9%) tested positive for PeV-A in 1 or more sites: 100 (77%) in blood, 84 (65%) in a nonsterile site, and 53 (41%) in cerebrospinal fluid (CSF). Five infants (4%) were CSF-only positive, 31 (24%) were blood-only positive, and 20 (15%) were nonsterile site-only positive. PeV-A3 was the most common type (85%) and the only type detected in CSF. Although the majority (79%) of infections were diagnosed between July and December, PeV-A was detected year-round. The median age at detection was 29 days. Fever (96%), fussiness (75%), and lymphopenia (56%) were common. Among infants with PeV-A-positive CSF, 77% had no CSF pleocytosis. The median duration of hospitalization was 41 hours. Four infants had bacterial coinfections diagnosed within 24 hours of admission; 40 infants had viral coinfections. CONCLUSIONS: Although most frequent in summer and fall, PeV-A infections were encountered in every calendar month within the 3-year period of study. More than one-half of patients had PeV-A detected at more than 1 body site. Coinfections were common. PeV-A3 was the most common type identified and the only type detected in the CSF.

Cerebrospinal Fluid Analysis for Viruses by Metagenomic Next-Generation Sequencing in Pediatric Encephalitis: Not Yet Ready for Prime Time?

BACKGROUND: Metagenomic next-generation sequencing offers an unbiased approach to identifying viral pathogens in cerebrospinal fluid of patients with meningoencephalitis of unknown etiology. METHODS: In an 11-month case series, we investigated the use of cerebrospinal fluid metagenomic next-generation sequencing to diagnose viral infections among pediatric hospitalized patients presenting with encephalitis or meningoencephalitis of unknown etiology. Cerebrospinal fluid from patients with known enterovirus meningitis were included as positive controls. Cerebrospinal fluid from patients with primary intracranial hypertension were included to serve as controls without known infections. RESULTS: Cerebrospinal fluid metagenomic next-generation sequencing was performed for 37 patients. Among 27 patients with encephalitis or meningoencephalitis, 4 were later diagnosed with viral encephalitis, 6 had non-central nervous system infections with central nervous system manifestations, 6 had no positive diagnostic tests, and 11 were found to have a noninfectious diagnosis. Metagenomic next-generation sequencing identified West Nile virus (WNV) in the cerebrospinal fluid of 1 immunocompromised patient. Among the 4 patients with known enterovirus meningitis, metagenomic next-generation sequencing correctly identified enteroviruses and characterized the viral genotype. No viral sequences were detected in the cerebrospinal fluid of patients with primary intracranial hypertension. Metagenomic next-generation sequencing also identified sequences of nonpathogenic torque Teno virus in cerebrospinal fluid specimens from 13 patients. CONCLUSIONS: Our results showed viral detection by cerebrospinal fluid metagenomic next-generation sequencing only in 1 immunocompromised patient and did not offer a diagnostic advantage over conventional testing. Viral phylogenetic characterization by metagenomic next-generation sequencing could be used in epidemiologic investigations of some viral pathogens, such as enteroviruses. The finding of torque Teno viruses in cerebrospinal fluid by metagenomic next-generation sequencing is of unknown significance but may merit further exploration for a possible association with noninfectious central nervous system disorders.

Tinea faciei caused by Trichophyton benhamiae in a child.

Tinea faciei is a common pediatric skin disease, most often caused by fungi of the genus Trichophyton. T benhamiae has been recently reclassified as a distinct species and is recognized as an emerging zoonotic dermatophyte with a wide range of possible infectious reservoirs worldwide. We present a previously healthy 7-year-old child presenting with unusual inflammatory facial plaques due to T benhamiae, confirmed by mass spectroscopy.

Pediatric Inpatient Problem List Review and Accuracy Improvement.

BACKGROUND AND OBJECTIVES: The problem list (PL) is a meaningful use-incentivized criterion for electronic health record documentation. Inconsistent use or inaccuracy of the PL can create communication gaps among providers, potentially leading to diagnostic delays and serious safety events. The objective of the study was to increase the rate of PL review by attending physicians for inpatients discharged from hospital pediatrics and infectious disease services from a baseline of 70% to 80% by June 2018 and to sustain the rate for 6 months. The secondary aim was to improve PL accuracy by decreasing the rate of duplicate codes and red code diagnoses that should resolve before discharge from a baseline of 12% and 11%, respectively, to 5% and sustaining the rate for 6 months. METHODS: A quality improvement team used the Institute for Healthcare Improvement Model for Improvement. We tracked duplicate codes and red codes as surrogate markers of PL quality. Rates of PL review and PL quality were analyzed monthly via statistical process control charts (p-charts) with 3-σ control limits to identify special cause variation. RESULTS: PL review improved from a baseline of 70% to 90%, and the change was sustained for 1 year. PL quality improved as duplicate codes at the time of discharge decreased from 12% to 6% and as red codes decreased from a baseline of 11% to 6%. CONCLUSIONS: The PL is an important communication tool that is underused. By engaging and educating stakeholders, incentivizing compliance, standardizing PL management, leveraging electronic health record enhancements, and providing physician feedback, we improved PL meaningful use and quality.