Hemagglutinin stalk-binding antibodies enhance effectiveness of neuraminidase inhibitors against influenza via Fc-dependent effector functions.

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.

Diagnostic Test Accuracy of Ultrasonography vs Computed Tomography for Papillary Thyroid Cancer Cervical Lymph Node Metastasis: A Systematic Review and Meta-analysis.

Importance: The use of ultrasonography (US) vs cross-sectional imaging for preoperative evaluation of papillary thyroid cancer is debated. Objective: To compare thyroid US and computed tomography (CT) in the preoperative evaluation of papillary thyroid cancer for cervical lymph node metastasis (CLNM), as well as extrathyroidal disease extension. Data Sources: MEDLINE and Embase were searched from January 1, 2000, to July 18, 2020. Study Selection: Studies reporting on the diagnostic accuracy of US and/or CT in individuals with treatment-naive papillary thyroid cancer for CLNM and/or extrathyroidal disease extension were included. The reference standard was defined as histopathology/cytology or imaging follow-up. Independent title and abstract review (2515 studies) followed by full-text review (145 studies) was completed by multiple investigators. Data Extraction and Synthesis: PRISMA guidelines were followed. Methodologic and diagnostic accuracy data were abstracted independently by multiple investigators. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool independently and in duplicate. Bivariate random-effects model meta-analysis and multivariable meta-regression modeling was used. Main Outcomes and Measures: Diagnostic test accuracy of US and CT of the neck for lateral and central compartment CLNM, as well as for extrathyroidal disease extension, determined prior to study commencement. Results: A total of 47 studies encompassing 31 942 observations for thyroid cancer (12 771 with CLNM; 1747 with extrathyroidal thyroid extension) were included; 21 and 26 studies were at low and high risk for bias, respectively. Based on comparative design studies, US and CT demonstrated no significant difference in sensitivity (73% [95% CI, 64%-80%] and 77% [95% CI, 67%-85%], respectively; P = .11) or specificity (89% [95% CI, 80%-94%] and 88% [95% CI, 79%-94%], respectively; P = .79) for lateral compartment CLNM. For central compartment metastasis, sensitivity was higher in CT (39% [95% CI, 27%-52%]) vs US (28% [95% CI, 21%-36%]; P = .004), while specificity was higher in US (95% [95% CI, 92%-98%]) vs CT (87% [95% CI, 77%-93%]; P < .001). Ultrasonography demonstrated a sensitivity of 91% (95% CI, 81%-96%) and specificity of 47% (95% CI, 35%-60%) for extrathyroidal extension. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that further study is warranted of the role of CT for papillary thyroid cancer staging, possibly as an adjunct to US.

An Advanced Nursing Directive for Children With Suspected Appendicitis: Protocol for a Quality Improvement Feasibility Study.

BACKGROUND: Pediatric appendicitis accounts for an estimated 7% to 10% of abdominal pain cases in the emergency department (ED). The diagnosis is time-consuming, and the investigative process depends on physician assessment, resulting in delays in diagnosis and therapeutic management. The utility of an advanced nursing directive (AND) to expedite this process is unclear and needs further exploration. OBJECTIVE: This study aims to describe key components of ED flow in patients with suspected appendicitis seen at a pediatric ED and pilot a directive that allows ED nurses to perform an order set that includes blood work, urine tests, analgesics, fluids, and an abdominal-pelvis ultrasound prior to physician assessment. METHODS: This study involves conducting a retrospective chart review alongside a quality improvement initiative to compare key ED flow metrics before and after AND implementation. Primary outcome measures include median time from ED triage assessment to ultrasound completion, analgesia administration, blood work results, and time to disposition (consult or discharge), alongside other key ED flow metrics for suspected appendicitis. Secondary outcomes will involve patient and caretaker satisfaction surveys. Descriptive statistics will be used to summarize the data. For differences in proportions, a chi-square test will be used. The Student t test will be used for continuous variables. A variable-controlled run chart will be performed to assess impact on ED flow metrics. Patient and family satisfaction surveys are administered immediately after the directive encounter and 7 days afterward. RESULTS: There are currently 3900 patients who have been screened, 344 patients who have been enrolled, and 90 patients who have received the medical directive since implementation in June 2020. Interim results on reduction of time to diagnostic and therapeutic ED flow parameters and satisfaction surveys are expected to be published in February 2022. The final study endpoint will be in June 2022. CONCLUSIONS: This study proposes a novel protocol for improving the diagnosis and treatment of suspected pediatric appendicitis through implementation of an evidence-based AND. This model may provide a standardized, international pathway for management of common pediatric and adult emergencies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33158.