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Anaphylaxis is an acute systemic and potentially fatal allergic reaction. In this study, we evaluated trends in yearly rates of anaphylaxis in a pediatric Emergency Department (ED) in Montreal, Canada.A prospective and retrospective recruitment process was used to find families of children who had presented with anaphylaxis at the Montreal Children's Hospital between April 2011 and April 2021. Using a uniform recruitment form, data were collected. Anaphylaxis patterns were compared to clinical triggers using descriptive analysis.Among 830,382 ED visits during the study period, 2726 (26% recruited prospectively) presented with anaphylaxis. The median age was 6 years (IQR: 0.2, 12.00), and 58.7% were males. The relative frequency of anaphylaxis cases doubled between 2011-2015, from 0.22% (95% CI, 0.19, 0.26) to 0.42 March 2020, the total absolute number of anaphylaxis cases and relative frequency declined by 24 cases per month (p0.05) and by 0.5% of ED visits (p0.05).The rate of anaphylaxis has changed over the years, representing modifications in food introduction strategies or lifestyle changes. The observed decrease in the frequency of anaphylaxis presenting to the ED during the COVID pandemic may reflect decreased accidental exposures with reduced social gatherings, the school closed, and reluctance to present to ED.

Prompt epinephrine autoinjector (EAI) use is the primary treatment for anaphylaxis. However, limited Canadian data exist on the impact of reaction location on EAI use for food-induced anaphylaxis (FIA).We sought to investigate the setting, management, and severity of pediatric FIA.We recruited children presenting with FIA from 11 Canadian emergency departments. Patient demographics and the setting, management, and symptoms of FIA were collected by standardized questionnaire. Factors associated with prehospital EAI use and reaction severity were determined by logistic regression.We recruited 3,604 children; 60.2% were male and the median age was 5.0 years (interquartile range 1.8-11.0). Among cases with a known location of FIA (85.0%), home was the most common setting (68.1%), followed by school/daycare (12.8%), other locations (11.4%; eg, park, car), and restaurants (7.4%). In the prehospital setting, EAI was administered in 36.7% of reactions at home, 66.7% in school/daycare, 40.2% in other locations, and 44.5% in restaurants. Relative to reactions occurring at school/daycare, prehospital EAI use was less likely at home (adjusted odds ratio [aOR] 0.80; 95% CI 0.76-0.84), in restaurants (aOR 0.81; 95% CI 0.75-0.87), and in other settings (aOR 0.77; 95% CI 0.73-0.83), when data were adjusted for reaction severity, sex, age, comorbidities, and province. The FIA setting was not associated with reaction severity or hospitalization.Prehospital EAI use was higher at school/daycare than in other settings, potentially owing to the presence of policies and training on FIA. Setting-specific interventions including educational programs and policies/laws mandating training and stocking an EAI may improve anaphylaxis recognition and treatment.

Data are sparse regarding tree nut-induced anaphylaxis (TNA).To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use.Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use.Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]).Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.

Sesame can cause severe allergic reactions and is a priority allergen in Canada.To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment.Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages.Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02).In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.

Intermediate filaments (IFs) are integral components of the cytoskeleton. They provide cells with tissue-specific mechanical properties and are involved in numerous cellular processes. Due to their intricate architecture, a 3D structure of IFs has remained elusive. Here we use cryo-focused ion beam milling, cryo-electron microscopy and tomography, to obtain a 3D structure of vimentin IFs (VIFs). VIFs assemble into a modular, densely-packed and highly-ordered helical symmetric structure of 40 α-helices in cross-section, organized into 5 protofibrils. Surprisingly, the intrinsically disordered head domains form an amyloid-like fiber in the center of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. Our findings demonstrate how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with striking strength and stretchability.

The discovery and characterization of antigen-specific CD8+ T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8+ T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell–depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.

Background: Caregiver hesitancy for their children to receive the COVID-19 vaccine remains due to concerns regarding safety and efficacy, but also due to fear of vaccine administration-related pain and distress. Study objectives were to determine caregivers’ perceptions regarding both their personal and child’s COVID-19 vaccine administration-related stress and fear and relate this to their likelihood to allow their child to receive COVID-19 vaccinations. Methods: This study was a secondary data analysis of a multicentre, cross-sectional survey of caregivers presenting to four Canadian pediatric emergency departments. Caregivers were surveyed between December 2020 and March 2021 and completed a digital survey on their own smartphones. Results: 331 caregivers responded to the survey (mean age 39.9 years [SD 7.71]); 74.2% (245/331) were mothers. Children’s mean age was 8.8 years [SD 5.4]; 49.8% (165/331) were female. 64.1% (209/326) of caregivers were willing to vaccinate their child against COVID-19, while 35.9% (117/326) were not. Greater perceived COVID-19 vaccine administration-related pain (0.88 [0.80; 0.95], p = .003) and stress (0.82 [0.76; 0.89], p = Conclusions: During the time period between COVID-19 pandemic waves 2 and 3, and after the vaccine had been federally approved for adults, one-third of Canadian caregivers surveyed reported being unwilling to vaccinate their child against COVID-19 in the future. Managing children’s and caregivers’ vaccine administration-related fear and stress may improve vaccine uptake for children.

QUESTION: I frequently see adolescents with recurrent abdominal pain in my family medicine clinic. While the diagnosis frequently is a benign condition such as constipation, I recently heard that after 2 years of recurrent pain, an adolescent was diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES). How is this condition diagnosed? What is the recommended treatment? ANSWER: Anterior cutaneous nerve entrapment syndrome, first described almost 100 years ago, is caused by entrapment of the anterior branch of the abdominal cutaneous nerve as it pierces the anterior rectus abdominis muscle fascia. The limited awareness of the condition in North America results in misdiagnosis and delayed diagnosis. Carnett sign—in which pain worsens when using a “hook-shaped” finger to palpate a purposefully tense abdominal wall—helps to confirm if pain originates from the abdominal viscera or from the abdominal wall. Acetaminophen and nonsteroidal anti-inflammatory drugs were not found to be effective, but ultrasound-guided local anesthetic injections seem to be an effective and safe treatment for ACNES, resulting in relief of pain in most adolescents. For those with ACNES and ongoing pain, surgical cutaneous neurectomy by a pediatric surgeon should be considered.

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

QUESTION: Headache, vomiting, lethargy, and seizures are common symptoms in healthy children with benign viral illnesses, but they are also signs that could represent a central nervous system (CNS) tumour. Primary care providers and guardians are hesitant to expose children to radiation associated with computed tomography scans or take on risks associated with the sedation frequently needed for magnetic resonance imaging. When should primary care providers order radiologic head imaging for children with common symptoms to identify those with a CNS tumour? ANSWER: Central nervous system tumours have no pathognomonic features, which often results in delays in diagnosis. Owing to the high prevalence of infratentorial tumours, children commonly present with symptoms of increased intracranial pressure, making a detailed history and a comprehensive physical examination, including ophthalmoscopy for papilledema, especially important. Magnetic resonance imaging is the criterion standard test but it may take time to access, and young children may need sedation. Hence, computed tomography may be a preferable first option. The HeadSmart initiative in the United Kingdom provides guidance to obtain brain imaging within 4 weeks of onset of persistent symptoms that are associated with CNS tumours. We advocate applying the same criteria in Canada in order to reduce delay in diagnosis of CNS tumours in children.

QUESTION: Ear piercing is one of the most common forms of body modification seen in children and adolescents presenting to my office. Parents of my younger pediatric patients inquire about potential post-piercing complications and risk factors associated with earlobe infections. What guidance should I give them? Also, are there any specific post-piercing complications to consider for older pediatric patients seeking second piercings in the upper cartilage area? ANSWER: Piercing the earlobe or auricular cartilage continues to be a popular procedure among children and adolescents. Despite its widespread practice, improper aseptic piercing technique, insufficient training, and trauma to the soft tissue during high-pressure piercing (eg, use of spring-loaded ear-piercing instruments) can increase one’s susceptibility to infections, bleeding, and microfractures. Other post-piercing complications include embedded earrings, keloids, hypertrophic scarring, and cutaneous hypersensitivity. Early recognition and treatment of infections and perichondritis secondary to transcartilaginous piercings can prevent the progression of severe ear deformities requiring reconstructive surgical interventions.

QUESTION: Un enfant de 1 an s’est présenté à ma clinique après être tombé du sofa et avoir atterri sur la tête. À la clinique, l’enfant était asymptomatique et agissait normalement. Cet enfant a-t-il besoin d’une imagerie de la tête? Si oui, comment décider entre une radiographie du crâne ou une tomodensitométrie (TDM) à l’hôpital? RÉPONSE: La règle de décision clinique du Pediatric Emergency Care Applied Research Network (PECARN) pour les TDM aide à identifier les enfants de moins de 2 ans qui présentent un risque élevé de blessure intracrânienne. L’application de la règle, qui a une sensibilité de 100% et une spécificité de 53,8% pour les lésions cérébrales traumatiques cliniquement importantes chez les enfants, est la première étape de l’évaluation des enfants qui présentent un traumatisme crânien mineur. Si la TDM d’urgence n’est pas nécessaire, il est recommandé que les enfants de moins de 2 ans reçoivent une radiographie du crâne seulement si une fracture du crâne est soupçonnée. La présence et le type de fracture du crâne déterminent si une TDM de la tête et une consultation en neurochirurgie sont justifiées.