Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards). 1st Edition.

These first Australian National Standards of Care for Childhood-onset Heart Disease (CoHD Standards) have been developed to inform the healthcare requirements for CoHD services and enable all Australian patients, families and carers impacted by CoHD (paediatric CoHD and adult congenital heart disease [ACHD]) to live their best and healthiest lives. The CoHD Standards are designed to provide the clarity and certainty required for healthcare services to deliver excellent, comprehensive, inclusive, and equitable CoHD care across Australia for patients, families and carers, and offer an iterative roadmap to the future of these services. The CoHD Standards provide a framework for excellent CoHD care, encompassing key requirements and expectations for whole-of-life, holistic and connected healthcare service delivery. The CoHD Standards should be implemented in health services in conjunction with the National Safety and Quality Health Service Standards developed by the Australian Commission on Safety and Quality in Health Care. All healthcare services should comply with the CoHD Standards, as well as working to their organisation's or jurisdiction's agreed clinical governance framework, to guide the implementation of structures and processes that support safe care.

Habitual prospective memory in preschool children.

Habitual prospective memory (PM) refers to situations in which individuals have to remember to perform a future task on a regular and frequent basis. Habitual PM tasks are ubiquitous and the ability to successfully complete these tasks (e.g., remembering to bring your lunch to school every day) is necessary for children as they begin to establish their own independence. The current investigation is the first to explore preschool children's ability to complete this kind of task. At the end of a regular testing session during which children engaged in a variety of unrelated cognitive tasks, participants were instructed to ask for a stamp on their card, which was sitting in a box on the table. Over the course of the first experiment, participants did this 13 times, spanning a time period of several months. The results demonstrated that children initially needed prompting from the experimenter to remember, but with experience, participants were able to retrieve this intention without assistance. Experiment 2 demonstrated that removing the box from participants' line of sight after numerous opportunities to perform the task did not negatively impact performance, although it did make a difference at the outset of this requirement to remember to ask for stamps. Together, these results indicate that with somewhat consistent and repeated practice, preschool children can fairly quickly demonstrate the ability to successfully perform future intentions that are likely to be repeated on numerous occasions.

Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised UNIVERSAL trial.

BACKGROUND: Whether ultrasound (US)-guided femoral access compared to femoral access without US guidance decreases access site complications in patients receiving a vascular closure device (VCD) is unclear. AIMS: We aimed to compare the safety of VCD in patients undergoing US-guided versus non-US-guided femoral arterial access for coronary procedures. METHODS: We performed a prespecified subgroup analysis of the UNIVERSAL trial, a multicentre randomised controlled trial of 1:1 US-guided femoral access versus non-US-guided femoral access, stratified for planned VCD use, for coronary procedures on a background of fluoroscopic landmarking. The primary endpoint was a composite of major Bleeding Academic Research Consortium 2, 3 or 5 bleeding and vascular complications at 30 days. RESULTS: Of 621 patients, 328 (52.8%) received a VCD (86% ANGIO-SEAL, 14% ProGlide). In patients who received a VCD, those randomised to US-guided femoral access compared to non-US-guided femoral access experienced a reduction in major bleeding or vascular complications (20/170 [11.8%] vs 37/158 [23.4%], odds ratio [OR] 0.44, 95% confidence interval [CI]: 0.23-0.82). In patients who did not receive a VCD, there was no difference between the US- and non-US-guided femoral access groups, respectively (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; interaction p=0.004). CONCLUSIONS: In patients receiving a VCD after coronary procedures, US-guided femoral access was associated with fewer bleeding and vascular complications compared to femoral access without US guidance. US guidance for femoral access may be particularly beneficial when VCD are used.

Short Message Service Reminder Nudge for Parents and Influenza Vaccination Uptake in Children and Adolescents With Special Risk Medical Conditions: The Flutext-4U Randomized Clinical Trial.

Importance: Children with chronic medical conditions are at increased risk of severe influenza. Uptake of influenza vaccination in children and adolescents with these identified special risk medical conditions (SRMCs) is suboptimal. Objective: To assess the effectiveness of Flutext-4U, a parent short message service (SMS) reminder nudge intervention, in increasing influenza immunization in children and adolescents with SRMCs. Design, Setting, and Participants: This randomized clinical trial was conducted at a tertiary pediatric hospital in Adelaide, South Australia, from April 15 to September 30, 2021. Children and adolescents aged 6 months to younger than 18 years with SRMCs and a subspecialist outpatient appointment over a 5-month period during the Australian seasonal influenza vaccination season (April-August 2021) were eligible to participate. Follow-up was until September 30, 2021. Interventions: Participants were randomly assigned (1:1 ratio) to control: clinician nudges (hospital vaccine availability, ease of access, and recommendation from hospital subspecialists) or SMS intervention (control conditions plus an additional SMS reminder nudge to parents), with randomization stratified by age group (<5 years, 5-14 years, or >14 to <18 years). Main Outcomes and Measures: The primary outcome was influenza vaccination, as confirmed by the Australian Immunisation Register. Results: A total of 600 participants (intervention group: 298 [49.7%]; mean [SD] age, 11.5 [4.6] years; 162 female participants [54.4%]; control group: 302 [50.3%]; mean [SD] age, 11.4 [4.7] years; 155 female participants [51.3%]) were included. Influenza vaccination was 38.6% (113 of 293) in the SMS intervention group compared with 26.2% (79 of 302) in the control group (adjusted odds ratio [aOR], 1.79; 95% CI, 1.27-2.55; P = .001). Time to vaccine receipt was significantly lower among SMS participants (adjusted hazard ratio, 1.67; 95% CI, 1.25-2.22; P < .001). For participants randomly assigned by June 15, a significantly greater proportion receiving the SMS intervention were vaccinated during the optimal delivery period April to June 30 (SMS group: 40.0% [76 of 190] vs 25.4% [50 of 197]; aOR, 1.97; 95% CI, 1.28-3.06; P = .002). Conclusions and Relevance: Results of this randomized clinical trial suggest that an additional SMS reminder nudge for parents delivered in the tertiary care hospital setting to children and adolescents with SMRCs resulted in higher influenza vaccine uptake compared with clinician nudges alone. Trial Registration: ANZCTR Identifier: ACTRN12621000463875.

Focality and prospective memory in preschool children.

We examined the influence of prospective memory (PM) cue focality in a sample of preschool children. Prior investigations in older populations indicated that focal targets were associated with enhanced PM performance, perhaps through more automatic retrieval processes. Importantly, this influential variable has not been thoroughly explored in younger samples. Over three test sessions, preschool children completed a memory task where they were shown a series of animals. During retrieval, participants were shown all of the animals except for one, and they had to name the missing animal. While engaged in this task, participants in the focal PM condition were instructed to remove particular animals (e.g., spider) from the game if they saw them. In the nonfocal condition, participants were told to remove any animal that was entirely one color (e.g., black) if they saw them during the game. The results demonstrated no difference in PM remembering between focal and nonfocal conditions. These results suggest that the effects of focality may not be present at the beginning stages of PM development. The implications for PM retrieval processes also are discussed.

Atrioventricular septal defect in Fontan circulation: Right ventricular dominance, not valve surgery, adversely affects survival.

OBJECTIVE: The effect of ventricular dominance and previous atrioventricular valve (AVV) surgery on patient outcomes after Fontan operation remains unclear. We sought to determine the effect of ventricular dominance and previous AVV surgery on transplantation-free survival and long-term AVV competency in patients with atrioventricular septal defect (AVSD) and Fontan circulation. METHODS: We conducted a retrospective study of 1703 patients in the Australia and New Zealand Fontan Registry, who survived Fontan operation between 1987 and 2021. RESULTS: Of 174 patients with AVSD, 60% (105/174) had right ventricular (RV) dominance and 40% (69/174) had left ventricular (LV) dominance. The cumulative incidence of moderate or greater AVV regurgitation at 25 years after Fontan operation in patients with LV dominance was 56% (95% CI, 35%-72%), compared with 54% (95% CI, 40%-67%) in patients with RV dominance (P = .6). Nonetheless, transplantation-free survival at 25 years in patients with LV dominance was 94% (95% CI, 86%-100%), compared with 67% (95% CI, 52%-87%) in patients with RV dominance (hazard ratio, 5.9; 95% CI, 1.4-25.4; P < .01). Of note, transplantation-free survival was not different in patients who underwent AVV surgery before or at Fontan completion compared with those who did not (15 years: 81% [95% CI, 62%-100%] vs 88% [95% CI, 81%-95%]; P = .3). CONCLUSIONS: In patients with AVSD and Fontan circulation the rate of moderate or greater common AVV regurgitation is similar in those with LV and RV dominance. RV dominance, rather than previous AVV surgery, is a risk factor for death or transplantation.

Design and Rationale of Routine UltrasouNd GuIdance for Vascular AccEss foR Cardiac Procedures: A Randomized TriaL (UNIVERSAL).

Background: A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared to radial access. Ultrasound (US)-guided femoral access may reduce major vascular complications and bleeding. We aim to determine whether routinely using US guidance for femoral arterial access for coronary angiography or intervention will reduce Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding or major vascular complications. Methods: The Ultrasound Guidance for Vascular Access for Cardiac Procedures: A Randomized Trial (UNIVERSAL) is a multicentre, prospective, open-label, randomized trial with blinded outcomes assessment. Patients undergoing coronary angiography with or without intervention via a femoral approach with fluoroscopic guidance will be randomized 1:1 to US-guided femoral access, compared to no US. The primary outcome is the composite of major bleeding based on the BARC 2, 3, or 5 criteria or major vascular complications within 30 days. The trial is designed to have 80% power and a 2-sided alpha level of 5% to detect a 50% relative risk reduction for the primary outcome based on a control event rate of 14%. Results: We completed enrollment on April 29, 2022, with 621 randomized patients. The patients had a mean age of 71 years (25.4% female), with a high rate of comorbidities, as follows: 45% had a prior percutaneous coronary intervention; 57% had previous coronary artery bypass surgery; and 18% had peripheral vascular disease. Conclusions: The UNIVERSAL trial will be one of the largest randomized trials of US-guided femoral access and has the potential to change guidelines and increase US uptake for coronary procedures worldwide.

Introduction: Par rapport à l'abord radial, la limitation importante de l'abord artériel fémoral lors des interventions au cœur pose un risque accru de complications vasculaires et de saignements. L'abord fémoral guidé par ultrasons (US) peut contribuer à réduire les complications vasculaires majeures et les saignements. Nous avons pour objectif de déterminer si l'utilisation systématique du guidage par US pour l'abord artériel fémoral lors des angiographies ou des interventions coronariennes contribuera à réduire les saignements de type 2, 3 ou 5 selon le B leeding A cademic R esearch C onsortium (BARC) ou les complications vasculaires majeures. Méthodes: L' U ltrasou n d Gu i dance for V ascular Acc e ss fo r Cardiac Procedure s : A Randomized Tria l (UNIVERSAL) est un essai multicentrique, prospectif, ouvert, à répartition aléatoire, réalisé par une évaluation à l'insu des résultats. Les patients subissant une angiographie coronarienne avec ou sans intervention par voie fémorale sous guidage fluoroscopique seront répartis de façon aléatoire 1:1 à l'abord fémoral guidé par US ou sans US. Le principal critère d'évaluation est le critère composite de saignements majeurs de type 2, 3 ou 5 selon les critères du BARC ou de complications vasculaires majeures dans les 30 jours. L'essai est conçu de façon à avoir une puissance de 80 % et un seuil alpha bilatéral de 5 % pour déterminer la réduction du risque relatif de 50 % du critère d'évaluation principal selon un taux d'événements dans le groupe témoin de 14 %. Résultats: Le 29 avril 2022, nous avons terminé le recrutement de 621 patients choisis aléatoirement. Les patients avaient un âge moyen de 71 ans (25,4 % de femmes) et un taux élevé de comorbidités : 45 % avaient déjà subi une intervention coronarienne percutanée, 57 % avaient déjà subi un pontage aorto-coronarien et 18 % avaient une maladie vasculaire périphérique. Conclusions: L'essai UNIVERSAL qui sera l'un des plus vastes essais à répartition aléatoire sur l'abord fémoral guidé par US a le potentiel de faire changer les lignes directrices et de faire augmenter le recours aux US lors des interventions coronariennes dans le monde entier.

Routine Ultrasonography Guidance for Femoral Vascular Access for Cardiac Procedures: The UNIVERSAL Randomized Clinical Trial.

Importance: A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared with radial access. Strategies to make femoral access safer are needed. Objective: To determine whether routinely using ultrasonography guidance for femoral arterial access for coronary angiography/intervention reduces bleeding or vascular complications. Design, Setting, and Participants: The Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures (UNIVERSAL) randomized clinical trial is a multicenter, prospective, open-label trial of ultrasonography-guided femoral access vs no ultrasonography for coronary angiography or intervention with planned femoral access. Patients were randomized from June 26, 2018, to April 26, 2022. Patients with ST-elevation myocardial infarction were not eligible. Interventions: Ultrasonography guidance vs no ultrasonography guidance for femoral arterial access on a background of fluoroscopic landmarking. Main Outcomes and Measures: The primary composite outcome is the composite of major bleeding based on the Bleeding Academic Research Consortium 2, 3, or 5 criteria or major vascular complications within 30 days. Results: A total of 621 patients were randomized at 2 centers in Canada (mean [SD] age, 71 [10.24] years; 158 [25.4%] female). The primary outcome occurred in 40 of 311 patients (12.9%) in the ultrasonography group vs 50 of 310 patients (16.1%) without ultrasonography (odds ratio, 0.77 [95% CI, 0.49-1.20]; P = .25). The rates of Bleeding Academic Research Consortium 2, 3, or 5 bleeding were 10.0% (31 of 311) vs 10.7% (33 of 310) (odds ratio, 0.93 [95% CI, 0.55-1.56]; P = .78). The rates of major vascular complications were 6.4% (20 of 311) vs 9.4% (29 of 310) (odds ratio, 0.67 [95% CI, 0.37-1.20]; P = .18). Ultrasonography improved first-pass success (277 of 311 [86.6%] vs 222 of 310 [70.0%]; odds ratio, 2.76 [95% CI, 1.85-4.12]; P < .001) and reduced the number of arterial puncture attempts (mean [SD], 1.2 [0.5] vs 1.4 [0.8]; mean difference, -0.26 [95% CI, -0.37 to -0.16]; P < .001) and venipuncture (10 of 311 [3.1%] vs 37 of 310 [11.7%]; odds ratio, 0.24 [95% CI, 0.12-0.50]; P < .001) with similar times to access (mean [SD], 114 [185] vs 129 [206] seconds; mean difference, -15.1 [95% CI, -45.9 to 15.8]; P = .34). All prerandomization prespecified subgroups were consistent with the overall finding. Conclusions and Relevance: In this randomized clinical trial, use of ultrasonography for femoral access did not reduce bleeding or vascular complications. However, ultrasonography did reduce the risk of venipuncture and number of attempts. Larger trials may be required to demonstrate additional potential benefits of ultrasonography-guided access. Trial Registration: ClinicalTrials.gov Identifier: NCT03537118.

Evaluation of serological assays for SARS-CoV-2 antibody testing from dried blood spots collected from cohorts with prior SARS-CoV-2 infection.

Background: Dried blood spot (DBS) specimens are a useful serosurveillance tool particularly in hard-to-reach populations but their application for detecting SARS-CoV-2 infection is poorly characterised. Objectives: To compare detection of naturally acquired SARS-CoV-2 antibodies in paired DBS and serum specimens using commercially available serological immunoassays. Study Design: Specimens were collected through St Vincent's Hospital observational post COVID-19 cohort study (ADAPT). Laboratory spotted DBS from venepuncture were initially tested on seven assays, a DBS validation completed on three with clinically collected fingerstick DBSs tested on one. Results: Sensitivity for Euroimmun nucleocapsid (NCP) IgG ELISA from laboratory spotted DBS (n=145), Euroimmun spike, IgG ELISA from laboratory spotted DBS (n=161), and Binding Site total antibody ELISA from clinically collected fingerstick DBS (n=391) was 100% (95% CI: 95.8-100%), 100% (95% CI: 95.8-100%) and 92.9% (95% CI: 89.5-95.5%), respectively. Specificity was 66.2% (95% CI: 53.6-77.0%), 96% (95% CI: 88.7-99.1%) and 98.8% (95% CI: 93.3-99.9%), respectively. All three assays' results displayed a strong positive correlation between DBS compared to paired serum. Conclusions: The Binding Site™ spike total antibody and Euroimmun™ spike IgG ELISAs provided good analytical performance, demonstrating that DBS specimens could facilitate specimen collection in the epidemiological surveillance of SARS-CoV-2 infection. This is highly applicable in populations and settings where venepuncture is problematic (including community based regional/remote settings, nursing homes, prisons, and schools).

Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma.

Aberrant methylation of genomic DNA has been reported in many cancers. Specific DNA methylation patterns have been shown to provide clinically useful prognostic information and define molecular disease subtypes with different response to therapy and long-term outcome. Osteosarcoma is an aggressive malignancy for which approximately half of tumors recur following standard combined surgical resection and chemotherapy. No accepted prognostic factor save tumor necrosis in response to adjuvant therapy currently exists, and traditional genomic studies have thus far failed to identify meaningful clinical associations. We studied the genome-wide methylation state of primary tumors and tested how they predict patient outcomes. We discovered relative genomic hypomethylation to be strongly predictive of response to standard chemotherapy. Recurrence and survival were also associated with genomic methylation, but through more site-specific patterns. Furthermore, the methylation patterns were reproducible in three small independent clinical datasets. Downstream transcriptional, in vitro, and pharmacogenomic analysis provides insight into the clinical translation of the methylation patterns. Our findings suggest the assessment of genomic methylation may represent a strategy for stratifying patients for the application of alternative therapies.

Using provider-parent strategies to improve influenza vaccination in children and adolescents with special risk medical conditions: a randomised controlled trial protocol.

INTRODUCTION: Influenza immunisation is a highly cost-effective public health intervention. Despite a comprehensive National Immunisation Program, influenza vaccination in children and adolescents with special risk medical conditions (SRMCs) is suboptimal. Flutext-4U is an innovative, multi-component strategy targeting paediatric hospitals, general practice and parents of children and adolescents with SRMC. The Flutext-4U study aims to assess the impact of Flutext-4U to increase influenza immunisation in children and adolescents with SRMC. METHODS AND ANALYSIS: This is a randomised controlled trial involving parents of children and adolescents (aged >6 months to <18 years) with SRMC receiving tertiary care at the Women's and Children's Hospital (WCH), Adelaide, South Australia, who are eligible for funded influenza immunisation with a hospital appointment between the start of the seasonal influenza vaccination season and 31 July 2021, their treating general practitioners (GPs), and WCH paediatric specialists.Parents (of children/adolescents with SRMC) are randomised (1:1 ratio) to standard care plus intervention (SMS reminder messages to parents; reminders (written correspondence) for their child's GP from the hospital's Paediatric Outpatients Department) or standard care (hospital vaccine availability, ease of access and reminders for WCH subspecialists) with randomisation stratified by age-group (<5, 5-14, >14 to <18 years).The primary outcome is influenza vaccination, as confirmed by the Australian Immunisation Register.The proportion vaccinated (primary outcome) will be compared between randomised groups using logistic regression, with adjustment made for age group at randomisation. The effect of treatment will be described using an OR with a 95% CI. ETHICS AND DISSEMINATION: The protocol and all study materials have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/20/WCHN/5). Results will be disseminated via peer-reviewed publication and at scientific meetings, professional and public forums. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000463875).

"Click"-Like η6 -Metalation/Demetalation of Aryl Iodides as a Means of Turning "ON/OFF" Halogen Bond Donor Functionality.

η6 -Metalated aryl halides are recognized as a class of halogen bond (XB) donors. Click-like η6 -metalation/demetalation of aryl iodides by cyclopentadienylruthenium(II) ([CpRuII ]+ ) is shown to turn ON/OFF (amplify/suppress) XB donor functionality. [CpRu(MeCN)3 ][PF6 ] is shown to react quantitatively with iodobenzenes (ArIn , n=1,2) to yield [CpRu(η6 -ArIn )][PF6 ] compounds. Photochemical demetalation (405 nm) quantitatively reverts these compounds to ArIn and [CpRu(MeCN)3 ][PF6 ]. Crystal structures of [CpRu(ArXn )]+ salts show that the [CpRu(ArIn )]+ cations are strong, charge-assisted XB donors analogous to iodopyridinium cations. XB-induced association of [CpRu(C6 H5 I)]+ with diazobicyclo[2.2.2]octane (DABCO) is established by NMR spectroscopy. [CpRu(C6 H5 I)][BPh4 ] and [CpRu(1,4-C6 H4 I2 )][BPh4 ] co-crystallize with DABCO and the structure of [CpRu(1,4-C6 H4 I2 )][BPh4 ]⋅DABCO⋅Et2 O is reported. DFT calculations support amplification of the XBing capabilities of aryl iodides upon [CpRu]+ -metalation.

Self-reported awareness of the legal status of eight responsibilities of dog owners in Ireland: are dog owners different from non-dog owners?

BACKGROUND: Legislation pertaining to canine ownership in Ireland maintains a one-health perspective by establishing a minimum standard of care for dogs while safeguarding human health and wellbeing. However, public awareness of this legislation has not been measured. The goals of this study were first, to estimate and compare the level of awareness, among dog owners and non-dog owners, that eight responsibilities of dog owners are prescribed by law in Ireland. Second, to determine if gender modifies differences in awareness between owners and non-owners, and third to determine whether gender itself is independently associated with awareness of the legal specification of these dog ownership responsibilities. RESULTS: We conducted a cross-sectional study of 679 University College Dublin employees. Exposure information included participants' dog ownership status, gender, age, and education level. Among dog owners and non-dog owners, we estimated and compared the prevalences of persons with self-reported awareness that each of eight dog ownership responsibilities are prescribed by law in Ireland: Dog fouling in a public place, the leashing and muzzling of certain breeds, holding a dog license, straying of dogs, safeguarding health and welfare of dogs, dog abandonment, prohibition on tail docking of puppies and the mandatory wearing of identification. The prevalence of awareness was low among both dog owners and non-dog owners with substantial awareness (≥ 80%) of only three responsibilities: Those pertaining to fouling, licensing and muzzling and leashing. Awareness that more than one responsibility was specified by law was also poor with only 17.9% (95% CI: 15.1-20.9%) of participants aware of all eight and dog owners essentially just as likely (54%; 95% CI: 49-58%) to be aware of more than one as non-dog owners. For most dog ownership responsibilities, differences in prevalence (PD) of awareness between owners and non-owners and females and males were trivial (PD < 10%). Similarly for most responsibilities, gender did not modify awareness PDs between owners and non-owners. CONCLUSIONS: In this well-educated university community, self-reported awareness that these eight responsibilities of dog owners are prescribed by law in Ireland is poor with essentially no difference between dog owners and non-dog owners or males and females. Awareness was higher for those responsibilities which, when not discharged, result in direct negative consequences to humans compared to those that result in direct negative consequences to dogs. It is likely that awareness of the legal status of these eight responsibilities of dog owners among the general public in Ireland is even less than observed in this study.

Pan-cancer landscape of CD274 (PD-L1) rearrangements in 283,050 patient samples, its correlation with PD-L1 protein expression, and immunotherapy response.

BACKGROUND: Immune checkpoint inhibitors (ICIs) benefit patients with multiple cancer types, however, additional predictive biomarkers of response are needed. CD274 (programmed cell death ligand-1, PD-L1) gene rearrangements are positively associated with PD-L1 expression and may confer benefit to ICI, thus a pan-cancer characterization of these alterations is needed. METHODS: We analyzed 283,050 patient samples across multiple tumor types that underwent comprehensive genomic profiling for activating CD274 rearrangements and other alterations. The DAKO 22C3 Tumor Proportion Scoring (TPS) method was used for PD-L1 immunohistochemistry (IHC) testing in a small subset with available data (n=55,423). A retrospective deidentified real-world clinico-genomic database (CGDB) was examined for ICI treatment outcomes. We also report a detailed case of CD274-rearranged metastatic rectal adenocarcinoma. RESULTS: We identified 145 samples with functional rearrangements in CD274. There were significant enrichments for PIK3CA, JAK2, PDCD1LG2, CREBBP, and PBRM1 co-mutations (ORs=2.1, 16.7, 17.8, 3.6, and 3.4, respectively, p<0.01). Genomic human papillomavirus (HPV)-16, Epstein-Barr virus, and mismatch repair genes also co-occurred (OR=6.2, 8.4, and 4.3, respectively, p<0.05). Median tumor mutational burden (TMB) was higher compared with CD274 wild-type samples (7.0 vs 3.5 mutations/Mb, p=1.7e-11), with disease-specific TMB enrichment in non-small cell lung, colorectal, unknown primary, and stomach cancers. PD-L1 IHC skewed toward positivity (N=39/43 samples with ≥1% positivity). Of eight patients from the CGDB, three remained on ICI treatment after 6 months. Separately, one patient with metastatic rectal adenocarcinoma experienced a pathologic complete response on chemoimmunotherapy. CONCLUSIONS: CD274 gene rearrangements are associated with increased PD-L1 IHC scores, higher TMB, and potential clinical benefit in ICI-treated patients with cancer.

Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States.

Asymptomatic SARS-CoV-2 infection and delayed implementation of diagnostics have led to poorly defined viral prevalence rates in the United States and elsewhere. To address this, we analyzed seropositivity in 9089 adults in the United States who had not been diagnosed previously with COVID-19. Individuals with characteristics that reflected the U.S. population (n = 27,716) were selected by quota sampling from 462,949 volunteers. Enrolled participants (n = 11,382) provided medical, geographic, demographic, and socioeconomic information and dried blood samples. Survey questions coincident with the Behavioral Risk Factor Surveillance System survey, a large probability-based national survey, were used to adjust for selection bias. Most blood samples (88.7%) were collected between 10 May and 31 July 2020 and were processed using ELISA to measure seropositivity (IgG and IgM antibodies against SARS-CoV-2 spike protein and the spike protein receptor binding domain). The overall weighted undiagnosed seropositivity estimate was 4.6% (95% CI, 2.6 to 6.5%), with race, age, sex, ethnicity, and urban/rural subgroup estimates ranging from 1.1% to 14.2%. The highest seropositivity estimates were in African American participants; younger, female, and Hispanic participants; and residents of urban centers. These data indicate that there were 4.8 undiagnosed SARS-CoV-2 infections for every diagnosed case of COVID-19, and an estimated 16.8 million infections were undiagnosed by mid-July 2020 in the United States.

Retrospective review of Kawasaki disease at the Women's and Children's Hospital, South Australia.

AIM: Kawasaki disease (KD) is one of the most common causes of acquired cardiac disease in children in high-income countries. The incidence of coronary artery disease (CAD), despite treatment with intravenous immunoglobulin, ranges from 5 to 20%. Determining risk factors for CAD may assist with management and reduce long-term complications. METHODS: Retrospective data were collected for all patients presenting to the Women's and Children's Hospital with a discharge diagnosis of KD over a 10.5-year period, from 2007 to 2018. RESULTS: A total of 141 patients were included in the review; 101 patients fulfilled complete criteria for KD; 25 incomplete criteria and 15 did not meet criteria but were treated for KD. CAD was present in 27.7% of all patients, ranging from ectasia to giant aneurysms based on Z-scores and echocardiogram descriptions. Medium to large aneurysms accounted for 8.5% of all patients with suspected KD. Patients with CAD were more likely to: fulfil incomplete criteria (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.7-10.8, P = 0.0027), be less than 12 months of age (OR 11.38, 95% CI 2.94-44.11, P = 0.0001), have CRP > 100 (OR 2.8, 95% CI 1.31-6.02, P = 0.0068) and have a delay in treatment (average day of illness prior to treatment 8.89 vs. 6.78 (OR 1.19, 95% CI 1.05-1.35, P = 0.0055)). Patients with a Kobayashi score ≥4 had a higher rate of re-treatment with intravenous immunoglobulin (OR 3.16, 95% CI 1.27-7.83, P = 0.013). CONCLUSION: Our data are consistent with previously reported risk factors, and high rates of CAD despite standard treatment.

Mapping a Pandemic: SARS-CoV-2 Seropositivity in the United States.

Asymptomatic SARS-CoV-2 infection and delayed implementation of diagnostics have led to poorly defined viral prevalence rates. To address this, we analyzed seropositivity in US adults who have not previously been diagnosed with COVID-19. Individuals with characteristics that reflect the US population (n = 11,382) and who had not previously been diagnosed with COVID-19 were selected by quota sampling from 241,424 volunteers (ClinicalTrials.gov NCT04334954). Enrolled participants provided medical, geographic, demographic, and socioeconomic information and 9,028 blood samples. The majority (88.7%) of samples were collected between May 10th and July 31st, 2020. Samples were analyzed via ELISA for anti-Spike and anti-RBD antibodies. Estimation of seroprevalence was performed by using a weighted analysis to reflect the US population. We detected an undiagnosed seropositivity rate of 4.6% (95% CI: 2.6 - 6.5%). There was distinct regional variability, with heightened seropositivity in locations of early outbreaks. Subgroup analysis demonstrated that the highest estimated undiagnosed seropositivity within groups was detected in younger participants (ages 18-45, 5.9%), females (5.5%), Black/African American (14.2%), Hispanic (6.1%), and Urban residents (5.3%), and lower undiagnosed seropositivity in those with chronic diseases. During the first wave of infection over the spring/summer of 2020 an estimate of 4.6% of adults had a prior undiagnosed SARS-CoV-2 infection. These data indicate that there were 4.8 (95% CI: 2.8-6.8) undiagnosed cases for every diagnosed case of COVID-19 during this same time period in the United States, and an estimated 16.8 million undiagnosed cases by mid-July 2020.

Doxycycline-induced idiopathic intracranial hypertension in a patient with Lyme disease.

ABSTRACT: Doxycycline is widely used to treat early and disseminated Lyme disease. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a rare but serious adverse reaction to this medication. This article reviews the pathophysiology, presentation, diagnosis, and treatment of a patient with disseminated Lyme disease complicated by doxycycline-induced IIH.