The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.
Objective: To provide a systematic review of the existing pediatric decannulation protocols, including the role of polysomnography, and their clinical outcomes.Methods: Five online databases were searched from database inception to May 29, 2020. Study inclusion was limited to publications that evaluated tracheostomy decannulation in children 18 years of age and younger. Data extracted included patient demographics and primary indication for tracheostomy. Methods used to assess readiness for decannulation were noted including the use of bronchoscopy, tracheostomy tube modifications, and gas exchange measurements. After decannulation, details regarding mode of ventilation, location, and length of observation period, and clinical outcomes were also collected. Descriptive statistical analyses were performed.Results: A total of 24 studies including 1395 children were reviewed.Tracheostomy indications included upper airway obstruction at a well-defined anatomic site (35%), upper airway obstruction not at a well-defined site (12%) and need for long-term ventilation and pulmonary care (53%). Bronchoscopy was routinely used in 23 of 24 (96%) protocols. Tracheostomy tube modifications in the protocols included capping (n = 20, 83%), downsizing (n = 14, 58%), and fenestrations (n = 2, 8%). Measurements of gas exchange included polysomnography (n = 13/18, 72%), oximetry (n = 10/18, 56%), blood gases (n = 3,17%), and capnography (n = 3, 17%). After decannulation, children in 92% of protocols were transitioned to room air. Observation period of 48 h or less was used in 76% of children.Conclusions: There exists large variability in pediatric decannulation protocols.Polysomnography plays an integral role in assessing most children for tracheostomy removal. Evidence-based guidelines to standardize pediatric tracheostomy care remain an urgent priority.
Children with chronic neurologic and chest wall diseases are at increased risk of postoperative respiratory complications. These complications include acute respiratory failure, atelectasis, pneumonia, need for reintubation, and need for tracheostomy and can carry significant negative impacts on patient outcomes, including mortality, and increased healthcare resource utilization. 1 As such, careful examination of risk factors in these complex children should be initiated in order to plan appropriate preoperative and postoperative interventions that help mitigate postoperative respiratory complications. Such interventions may preoperatively include initiation of respiratory support devices such as non-invasive ventilation (NIV) and airway clearance techniques and/or a plan
OBJECTIVE Chiari malformation type I (CM-I) involves the herniation of the cerebellar tonsils through the foramen magnum. CM-I is associated with both obstructive sleep apnea (OSA) and central sleep apnea (CSA) in children. The primary management of symptomatic CM-I remains surgical decompression. There is, however, a paucity of data evaluating the efficacy of decompression surgery on outcomes related to sleep-disordered breathing (SDB). The objective of this study was to evaluate SDB outcomes, specifically the need for respiratory support following decompression in pediatric patients with CM-I. METHODS This was a retrospective chart review of all children diagnosed with CM-I when younger than 18 years of age who had polysomnography (PSG) studies pre- and postsurgery, between January 2008 and October 2018 at the Hospital for Sick Children in Toronto. Patient demographics, symptoms, PSG data, ongoing respiratory support, and surgical notes were recorded. Differences in PSG studies obtained pre- and postsurgery were compared using the Wilcoxon test for paired samples. RESULTS A total of 15 children with 15 interventions met inclusion criteria with pre- and postsurgery PSG studies and were considered for statistical analysis. Of the 15 subjects included for analysis, preoperative OSA was present in 2 (13.3%), CSA in 5 (33.3%), mixed SDB (both OSA and CSA) in 4 (26.7%), and no significant SDB in 4 (26.7%). Postoperatively, OSA was present in 3 (20.0%), CSA in 4 (26.7%), mixed SDB in 0 (0%), and no significant SDB in 8 (53.3%). The presence of severe OSA decreased from 4/15 (26.7%) to 2/15 (13.3%) postoperatively, and severe CSA decreased from 5/15 (33.3%) to 2/15 (13.3%) postoperatively. Following decompression surgery, 7/15 subjects (46.7%) required positive airway pressure for management of their SDB. Overall, significant improvements were observed in a number of respiratory parameters following decompression including the following: the total apnea-hypopnea index (AHI) (17.5 ± 48.2 vs 6.1 ± 32.7 events/hour; p = 0.001), obstructive AHI (2.1 ± 16.1 vs 1.0 ± 6.6 events/hour; p = 0.005), central AHI (6.3 ± 48.9 vs 2.7 ± 33.0 events/hour; p = 0.005), and the desaturation index (16.7 ± 49.6 vs 3.8 ± 25.3; p = 0.001). CONCLUSIONS Although decompression surgery led to a significant reduction in obstructive and central events, many children continued to have persistent SDB and required additional positive airway pressure therapy. This information is important and relevant for anticipatory guidance around decompression surgery and the necessity for respiratory support for the management of SDB in pediatric patients with CM-I.
Murine Ly49 receptors, which are expressed mainly on NK and NKT cells, interact with MHC class I (MHC-I) molecules with varying specificity. Differing reports of Ly49/MHC binding affinities may be affected by multiple factors, including cis versus trans competition and species origin of the MHC-I L chain (β2-microglobulin). To determine the contribution of each of these factors, Ly49G, Ly49I, Ly49O, Ly49V, and Ly49Q receptors from the 129 mouse strain were expressed individually on human 293T cells or the mouse cell lines MHC-I–deficient C1498, H-2b–expressing MC57G, and H-2k–expressing L929. The capacity to bind to H-2Db– and H-2Kb–soluble MHC-I tetramers containing either human or murine β2-microglobulin L chains was tested for all five Ly49 receptors in all four cell lines. We found that most of these five inhibitory Ly49 receptors show binding for one or both self–MHC-I molecules in soluble tetramer binding assays when three conditions are fulfilled: 1) lack of competing cis interactions, 2) tetramer L chain is of mouse origin, and 3) Ly49 is expressed in mouse and not human cell lines. Furthermore, Ly49Q, the single known MHC-I receptor on plasmacytoid dendritic cells, was shown to bind H-2Db in addition to H-2Kb when the above conditions were met, suggesting that Ly49Q functions as a pan–MHC-Ia receptor on plasmacytoid dendritic cells. In this study, we have optimized the parameters for soluble tetramer binding analyses to enhance future Ly49 ligand identification and to better evaluate specific contributions by different Ly49/MHC-I pairs to NK cell education and function.
Objectives: To describe the current clinical practice patterns of Canadian pediatric respirologists at pediatric tertiary care institutions regarding chronic tracheostomy tube care and management of home invasive ventilation. Methods: A pediatric respirologist/pediatrician with expertise in tracheostomy tube care and home ventilation was identified at each Canadian pediatric tertiary care center to complete a 59-item survey of multiple choice and short answer questions. Domains assessed included tracheostomy tube care, caregiver competency and home monitoring, speaking valves, medical management of tracheostomy complications, decannulation, and long-term follow-up. Results: The response rate was 100% (17/17) with all Canadian tertiary care pediatric centers represented and heterogeneity of practice was observed in all domains assessed. For example, though most centers employ Bivona™ (17/17) and Shiley™ (15/17) tracheostomy tubes, variability was observed around tube change, re-use, and cleaning practices. Most centers require two trained caregivers (14/17) and recommend 24/7 eyes on care and oxygen saturation monitoring. Discharge with an emergency tracheostomy kit was universal (17/17). Considerable heterogeneity was observed in the timing and use of speaking valves and speech-language assessment. Inhaled anti-pseudomonal antibiotics are employed by most centers (16/17) though the indication, agent, and protocol varied by center. Though decannulation practices varied considerably, the requirement of upper airway patency was universally required to proceed with decannulation (17/17) independent of ongoing ventilatory support requirements. Conclusion: Considerable variability in pediatric tracheostomy tube care practice exists across Canada. These results will serve as a starting point to standardize and evaluate tracheostomy tube care nationally.
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