Platelet-activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children.

BACKGROUND: There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet-activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet-activating factor pathway in pediatric patients with anaphylaxis. METHODS: Forty-six pediatric patients (<18 years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow-up >4 weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. RESULTS: Severe anaphylaxis was experienced by 12/46 (26%) and mild-moderate anaphylaxis in 34/46 (74%) children. Platelet-activating factor acetylhydrolase (PAF-AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF-AH activity as compared with 14/34 with mild-moderate anaphylaxis (p < .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF-AH (nmol/ml/min) (13.73, 95%CI: 7.42-20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80-18.83; p < .05). In children with anaphylaxis, PAF-AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10-18.42 vs 17.50, 95%CI: 16.21-18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21-20.21; p < .05). CONCLUSION: Decreased serum PAF-AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF-AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Nivolumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Retrospective Tertiary Centre's Real-World Experience.

Nivolumab, a PD-1 checkpoint inhibitor, was approved in Canada in 2017 for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on the phase 3 trial CHECKMATE-141. We aimed to examine the demographics and efficacy of nivolumab in a Canadian, real-world setting. A retrospective chart review was performed on patients who received nivolumab for R/M HNSCC from 2017 to 2020 at a high-volume cancer centre. Data were abstracted from 34 patients, based on physician notes and imaging reports. The median patient age at nivolumab initiation was 61, 24% were female, and 62% were current or former smokers. Prior to nivolumab, 44% of patients underwent surgery, 97% radiation, and 100% chemotherapy. Most (97%) therapies were for primary disease. Overall survival at 6 and 12 months following drug initiation was 38% and 23%, respectively. Progression-free survival at 6 and 12 months was 33% and 22%, respectively. Eighteen percent of patients experienced an immune-related adverse event, the most common of which was pneumonitis (3/8) and endocrine events (3/8). Seven out of eight of the immune adverse events were grade 1-2; 1/8 was grade 3. Nivolumab appears to have decreased survival rates in our single-centre Canadian population compared to CHECKMATE-141 and presented a manageable adverse event profile for R/M HNSCC.

Enhancing Outpatient Symptom Management in Patients With Head and Neck Cancer: A Qualitative Analysis.

IMPORTANCE: Patients with head and neck cancer manage a variety of symptoms at home on an outpatient basis. Clinician review alone often leaves patient symptoms undetected and untreated. Standardized symptom assessment using patient-reported outcomes (PROs) has been shown in randomized clinical trials to improve symptom detection and overall survival, although translation into real-world settings remains a challenge. OBJECTIVE: To better understand how patients with head and neck cancer cope with cancer-related symptoms and to examine their perspectives on standardized symptom assessment. DESIGN, PARTICIPANTS, AND SETTING: This was a qualitative analysis using semistructured interviews of patients with head and neck cancer and their caregivers from November 2, 2020, to April 16, 2021, at a regional tertiary center in Canada. Purposive sampling was used to recruit a varied group of participants (cancer subsite, treatment received, sociodemographic factors). Drawing on the Supportive Care Framework, a thematic approach was used to analyze the data. Data analysis was performed from November 2, 2020, to August 2, 2021. MAIN OUTCOMES AND MEASURES: Patient perception of ambulatory symptom management and standardized symptom assessment. RESULTS: Among 20 participants (median [range] age, 59.5 [33-74] years; 9 [45%] female; 13 [65%] White individuals), 4 themes were identified: (1) timely physical symptom management, (2) information as a tool for symptom management, (3) barriers to psychosocial support, and (4) external factors magnifying symptom burden. Participants' perceptions of standardized symptom assessment varied. Some individuals described the symptom monitoring process as facilitating self-reflection and symptom detection. Others felt disempowered by the process, particularly when symptom scores were inconsistently reviewed or acted on. CONCLUSIONS AND RELEVANCE: This qualitative analysis provides a novel description of head and neck cancer symptom management from the patient perspective. The 4 identified themes and accompanying recommendations serve as guides for enhanced symptom monitoring.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.