Body Mass Index and Postacute Sequelae of SARS-CoV-2 Infection in Children and Young Adults.

Importance: Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear. Objective: To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity. Design, Setting, and Participants: This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with SARS-CoV-2 infection. Data analysis was conducted from October 2023 to January 2024. Exposures: BMI status assessed within 18 months before infection; the measure closest to the index date was selected. The BMI categories included healthy weight (≥5th to <85th percentile for those aged 5-19 years or ≥18.5 to <25 for those aged >19 years), overweight (≥85th to <95th percentile for those aged 5-19 years or ≥25 to <30 for for those aged >19 years), obesity (≥95th percentile to <120% of the 95th percentile for for those aged 5-19 years or ≥30 to <40 for those aged >19 years), and severe obesity (≥120% of the 95th percentile for those aged 5-19 years or ≥40 for those aged >19 years). Main Outcomes And Measures: To identify PASC, a diagnostic code specific for post-COVID-19 conditions was used and a second approach used clusters of symptoms and conditions that constitute the PASC phenotype. Relative risk (RR) for the association of BMI with PASC was quantified by Poisson regression models, adjusting for sociodemographic, acute COVID severity, and other clinical factors. Results: A total of 172 136 participants (mean [SD] age at BMI assessment 12.6 [4.4] years; mean [SD] age at cohort entry, 13.1 [4.4] years; 90 187 female [52.4%]) were included. Compared with participants with healthy weight, those with obesity had a 25.4% increased risk of PASC (RR, 1.25; 95% CI, 1.06-1.48) and those with severe obesity had a 42.1% increased risk of PASC (RR, 1.42; 95% CI, 1.25-1.61) when identified using the diagnostic code. Compared with those with healthy weight, there was an increased risk for any occurrences of PASC symptoms and conditions among those with obesity (RR, 1.11; 95% CI, 1.06-1.15) and severe obesity (RR, 1.17; 95% CI, 1.14-1.21), and the association held when assessing total incident occurrences among those with overweight (RR, 1.05; 95% CI, 1.00-1.11), obesity (RR, 1.13; 95% CI, 1.09-1.19), and severe obesity (RR, 1.18; 95% CI, 1.14-1.22). Conclusions And Relevance: In this cohort study, elevated BMI was associated with a significantly increased PASC risk in a dose-dependent manner, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults.

Combined Pediatric Rheumatology/Dermatology Clinics: Benefits and Challenges.

BACKGROUND/OBJECTIVES: Integrated care models, like combined rheumatology/dermatology clinics (RDCs), facilitate efficient coordination between specialists and provide comprehensive care. Given the limited literature on pediatric RDC logistics, outcomes, benefits and, challenges, we comprehensively characterized our patient cohort at the UCSF Benioff Children's Hospital RDC and surveyed pediatric dermatologists participating in RDCs. METHODS: We retrospectively reviewed 71 patients new to the UCSF Pediatric RDC between September 2017 and September 2023. A survey was distributed in 2024 to 17 dermatologists in North America, each representing a unique pediatric RDC. RESULTS: 69% of patients (49/71) were female. Seventeen (24%) presented without a known diagnosis; the first RDC visit established a diagnosis for 7 of them (41%). Of patients with a previously established diagnosis, initial RDC evaluation confirmed it in 52 (96%) and revised it for 2 (4%). The most encountered diagnoses were linear morphea (33%), lupus (23%), and psoriasis (13%). New systemic therapy was prescribed for 23% of patients, and additional work-up was recommended via skin biopsy (8%) and imaging (28%). Survey results revealed all pediatric RDCs include trainees, but only 59% (10/17) receive administrative support. All agreed that RDCs are valuable for patient care and most (15/17, 88%) felt that the RDC was a valuable use of their time. CONCLUSIONS: Pediatric RDCs are valuable for consensus diagnosis, streamlined evaluation, and management of complex patients. Though clinical and administrative support for RDCs is generally poor, RDCs are valuable to patients, a good use of time for clinicians, and offer educational opportunities for team members.

Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4ß7-Blocking Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response. METHODS: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4ß7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell variable, diversity, and joining sequencing; serum proteomics; and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response. RESULTS: Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4+ memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4ß1, potentially making these cells less susceptible to direct targeting by vedolizumab. CONCLUSIONS: These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.

Neutrophil extracellular traps in homeostasis and disease.

Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the progression and exacerbation of various pathological states. Nevertheless, NETs exhibit dual functionalities in certain pathological contexts. While NETs may act as autoantigens, aggregated NET complexes can function as inflammatory mediators by degrading proinflammatory cytokines and chemokines. The delineation of molecules and signaling pathways governing NET formation aids in refining our appreciation of NETs' role in immune homeostasis, inflammation, autoimmune diseases, metabolic dysregulation, and cancer. In this comprehensive review, we delve into the multifaceted roles of NETs in both homeostasis and disease, whilst discussing their potential as therapeutic targets. Our aim is to enhance the understanding of the intricate functions of NETs across the spectrum from physiology to pathology.

Donor Characteristics and Outcomes of Pediatric Heart Transplantation in South Korea.

BACKGROUND: Heart transplantation is often limited by the availability of transplantable donor heart and understanding of donor aspects that would influence transplant outcomes becomes important. In this study, donor characteristics and their impact on the outcomes of pediatric heart transplantations performed in South Korea were investigated. METHODS: We reviewed the medical records of patients less than 18 years old who received heart transplantation between 2002 and 2022 in three tertiary hospitals located in South Korea. RESULTS: A total of 139 cases were enrolled. One-year mortality was 10.4% and total mortality was 33.8%. Forty-nine recipients (35.3%) showed biopsy-proven rejections and 20 (14.4%) showed cardiac allograft vasculopathy during mean follow-up of 6.4 ± 4.9 years. Six recipients (4.5%) showed left ventricle ejection fraction of less than 55% post-transplantation. The mean age of the donors was 23.0 ± 15.4 years. The most common cause of death of the donors was unspecified illness (46.4%). Donors with a history of diabetes, hypertension, smoking, and alcohol consumption were 0%, 3.1%, 32.1%, and 34.4%, respectively. Mean total ischemic time was 191.6 ± 72.7 min, while total ischemic time was over 4 h in 37 patients (26.6%). There were no significant relationship between donor factors and survival. However, donor's history of drinking or cardiopulmonary resuscitation was significantly associated with acute rejection and donor's age with cardiac allograft vasculopathy. CONCLUSION: Donor factors did not show significant impact on post-transplant survival but some factors were predictive of post-transplant rejection and cardiac allograft vasculopathy.

Efficacy and Safety of Pharmacokinetically-Driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis-A Double-Blind Placebo Controlled Clinical Trial (The Pediatric Lupus Nephritis Mycophenolate Mofetil Study).

Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability. Methods/Design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention. Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

Childhood Arthritis and Rheumatology Research Alliance Biologic Disease-Modifying Antirheumatic Drug Consensus Treatment Plans for Refractory Moderately Severe Juvenile Dermatomyositis.

OBJECTIVE: The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM. RESULTS: Four bDMARD CTPs were proposed: tumor necrosis factor α (TNFα) inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67 of 72]) as well as for patient characteristics, assessments, outcome measures, and follow-up. By weighted average, respondents indicated that they would most likely administer rituximab, followed by abatacept, TNFα inhibitor, and tocilizumab. CONCLUSION: CTPs for the administration of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.

Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project.

Background: The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19. Methods: This retrospective cohort study used data from the RECOVER consortium comprising 19 US children's hospitals and health institutions between March 2020 and September 2023. Every participant had at least a six-month follow-up after cohort entry. Absolute risks of incident post-acute COVID-19 sequelae were reported. Relative risks (RRs) were calculated by contrasting COVID-19-positive with COVID-19-negative groups using a Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through propensity scoring stratification. Results: A total of 1,213,322 individuals under 21 years old (mean[SD] age, 7.75[6.11] years; 623,806 male [51.4%]) were included. The absolute rate of any post-acute cardiovascular outcome in this study was 2.32% in COVID-19 positive and 1.38% in negative groups. Patients with CHD post-SARS-CoV-2 infection showed increased risks of any cardiovascular outcome (RR, 1.63; 95% confidence interval (CI), 1.47-1.80), including increased risks of 11 of 18 post-acute sequelae in hypertension, arrhythmias (atrial fibrillation and ventricular arrhythmias), myocarditis, other cardiac disorders (heart failure, cardiomyopathy, and cardiac arrest), thrombotic disorders (thrombophlebitis and thromboembolism), and cardiovascular-related symptoms (chest pain and palpitations). Those without CHDs also experienced heightened cardiovascular risks after SARS-CoV-2 infection (RR, 1.63; 95% CI, 1.57-1.69), covering 14 of 18 conditions in hypertension, arrhythmias (ventricular arrhythmias and premature atrial or ventricular contractions), inflammatory heart disease (pericarditis and myocarditis), other cardiac disorders (heart failure, cardiomyopathy, cardiac arrest, and cardiogenic shock), thrombotic disorders (pulmonary embolism and thromboembolism), and cardiovascular-related symptoms (chest pain, palpitations, and syncope). Conclusions: Both children with and without CHDs showed increased risks for a variety of cardiovascular outcomes after SARS-CoV-2 infection, underscoring the need for targeted monitoring and management in the post-acute phase.

Safety and feasibility of intravenous sotalol loading for the prevention of ventricular arrhythmias.

BACKGROUND: The use of intravenous (IV) sotalol loading following recent U.S. Food and Drug Administration (FDA) approval of a 1-day loading protocol has reduced the obligatory 3-day hospital stay for sotalol initiation when given orally. Several studies have recently demonstrated the safety and feasibility of IV loading for patients with atrial arrhythmias. However, there is a paucity of data on the feasibility and safety of IV sotalol loading for patients with ventricular arrhythmias. This study aims to assess the safety, feasibility, and length of stay (LOS) outcomes of IV sotalol loading for the prevention of ventricular arrhythmias. METHODS: A retrospective analysis was performed of all patients undergoing IV sotalol loading and oral sotalol initiation for ventricular arrhythmias, or IV sotalol loading for atrial arrhythmias between August 2021 and December 2023 at Northwestern University. Baseline characteristics, success of sotalol initiation/loading, changes in heart rate (HR) and QT/QTc, safety, and LOS were compared between patients undergoing sotalol loading/initiation for ventricular arrhythmias (IV vs. PO) and between patients undergoing IV sotalol loading for ventricular arrhythmias vs. for atrial arrhythmias. RESULTS: A total of 28 patients underwent sotalol loading/initiation for ventricular arrhythmias (N = 15 IV and N = 13 PO) and 41 patients underwent IV sotalol loading for atrial arrhythmias. Baseline characteristics of congestive heart failure history and left ventricular ejection fraction were worse in the ventricular arrhythmias group. There was no significant difference in the successful completion of IV sotalol loading for ventricular arrhythmias compared to oral sotalol initiation for ventricular arrhythmias or IV sotalol loading for atrial arrhythmias (86.7% vs. 92.3% vs. 90.2%, p = 0.88). There was a significant increase in ΔQTc following IV sotalol infusion for ventricular arrhythmias compared to following PO sotalol initiation for ventricular arrhythmias (46.4 ± 29.2 ms vs. 8.9 ± 32.6 ms, p = 0.004) and following IV sotalol infusion for atrial arrhythmias (46.4 ± 29.2 ms vs. 24.0 ± 25.1 ms, p = 0.018). ΔHR following IV sotalol infusion for ventricular arrhythmias was similar to ΔHR following PO sotalol initiation for ventricular arrhythmias and ΔHR following IV sotalol infusion for atrial arrhythmias (- 7.5 ± 8.7 bpm vs. - 8.5 ± 13.9 bpm vs. - 8.3 ± 13.2 bpm, p = 0.87). There were no significant differences in discontinuation for QTc prolongation (6.7% vs. 1.7% vs. 2.4%, p = 0.64) and bradycardia (13.3% vs. 7.7% vs. 9.8%, p = 0.88) between IV sotalol loading for ventricular arrhythmias, PO sotalol initiation for ventricular arrhythmias, and IV sotalol loading for atrial arrhythmias. There were no instances of hypotension, life-threatening ventricular arrhythmias, heart failure, or death. Length of stay was significantly shorter for IV sotalol loading compared to PO sotalol initiation for ventricular arrhythmias (1.1 ± 0.36 days vs. 4.2 ± 1.0 days, p < 0.0001). CONCLUSION: IV sotalol loading appears feasible and safe for use in ventricular arrhythmias and results in a decreased length of stay. Despite increased comorbidities and greater increase in QTc interval following IV sotalol infusion in the ventricular arrhythmias group, there were no significant differences in successful completion of loading or adverse outcomes when compared to PO sotalol initiation for ventricular arrhythmias and IV loading for atrial arrhythmias.

Coordinated immune dysregulation in juvenile dermatomyositis revealed by single-cell genomics.

Juvenile dermatomyositis (JDM) is one of several childhood-onset autoimmune disorders characterized by a type I IFN response and autoantibodies. Treatment options are limited due to an incomplete understanding of how the disease emerges from dysregulated cell states across the immune system. We therefore investigated the blood of patients with JDM at different stages of disease activity using single-cell transcriptomics paired with surface protein expression. By immunophenotyping peripheral blood mononuclear cells, we observed skewing of the B cell compartment toward an immature naive state as a hallmark of JDM at diagnosis. Furthermore, we find that these changes in B cells are paralleled by T cell signatures suggestive of Th2-mediated inflammation that persist despite disease quiescence. We applied network analysis to reveal that hyperactivation of the type I IFN response in all immune populations is coordinated with previously masked cell states including dysfunctional protein processing in CD4+ T cells and regulation of cell death programming in NK cells, CD8+ T cells, and γδ T cells. Together, these findings unveil the coordinated immune dysregulation underpinning JDM and provide insight into strategies for restoring balance in immune function.

Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.

The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections.

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN-), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN- reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN-. In this review, we discuss roles of HOSCN/SCN- in immunity and potential therapeutic implications for combating infections.

Mental health in paediatric and adult myositis-related diseases: current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group.

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking.Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Metformin-associated lactic acidosis (MALA): Is it an underestimated entity? A retrospective, single-center case series.

INTRODUCTION: Metformin is widely considered a first-line antiglycemic agent due to its cost-effectiveness and favorable adverse effect profile. However, its use is prohibited in patients with an estimated glomerular filtration rate <30 mL/min/1.73 m2 , due to the risk of potentially lethal metformin-associated lactic acidosis (MALA). We sought to evaluate MALA cases and outcomes at our institution. METHODS: In this observational, retrospective case series, we reviewed our EMR for all patients who had a metformin level drawn between January 2013 and May 2022 to identify individuals who met the diagnostic criteria for MALA. We evaluated risk factors for MALA, the relationship between metformin level, blood pH, serum bicarbonate, and lactate level and clinical outcomes of ventilator dependency, renal replacement therapy requirement, renal recovery in acute kidney injury (AKI) patients, and survival. FINDINGS: A total of 107 patients had metformin levels drawn, of which 19 patients met the diagnostic criteria for MALA. In our case series, MALA was primarily seen in AKI (15 patients) secondary to dehydration and sepsis, followed by end-stage renal disease (ESRD) (4 patients). Intubation was required in 17 patients, of whom 8 were successfully extubated after a mean duration of 14 days. Sixteen patients received renal replacement therapy (RRT). Intermittent hemodialysis (IHD) was performed in nine, continuous renal replacement therapy (CRRT) in four, and sequential therapy of IHD and CRRT in three patients. Seven patients, all in the AKI group (46.7%), died while all ESRD patients survived, accounting for an overall mortality rate of 36.8%. Among the eight surviving AKI patients, four had complete renal recovery with renal function returning to baseline, three had partial renal recovery, and one continued to require IHD at the time of discharge to a rehabilitation facility. DISCUSSION: MALA may be an underrecognized entity. A high level of clinical suspicion leading to prompt and aggressive treatment with RRT may improve mortality rates. Provider and patient education is of paramount importance for safe use of metformin.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis in children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Which parents provide zero-alcohol beverages to adolescents? A survey of Australian parents' practices and intentions.

OBJECTIVE: Zero-alcohol beverages (<0.5% alcohol by volume) appear and taste similar to alcoholic beverages but are regulated similarly to soft drinks in many countries, blurring the distinction between alcoholic and non-alcoholic beverages. How parents view provision of zero-alcohol beverages to adolescents is likely a key determinant of adolescent consumption. We investigated factors associated with parents' provision of zero-alcohol beverages to adolescents, including attitudes toward zero-alcohol beverages and demographic, knowledge, and behavioural factors known to be associated with provision of alcoholic beverages. METHODS: We conducted an online cross-sectional survey of N = 1197 Australian parents of adolescents aged 12-17 years in April-May 2022. We examined associations with zero-alcohol beverage provision using binomial logistic regression, and with future provision intentions using multinomial logistic regression analyses. RESULTS: Factors significantly associated (p < .001) with parents' provision and future intentions to provide zero-alcohol beverages to their adolescent included beliefs that zero-alcohol beverages had benefits for adolescents (Adjusted Odds Ratio [AOR] 2.69 (provision); 3.72 (intentions)), provision of alcoholic beverages (AOR 2.67 (provision); 3.72 (intentions)), and an incorrect understanding of alcohol guidelines for adolescents (AOR 2.38 (provision); 1.95 (intentions)). CONCLUSIONS: Parents' provision and intentions to provide zero-alcohol beverages were associated with beliefs about zero-alcohol beverages as well as some factors associated with provision of alcoholic beverages. Precautionary advice to parents that the provision of zero-alcohol beverages may serve to normalise alcohol consumption may be warranted.