Revisiting the Applicability of Adult Early Post-Operative Nausea and Vomiting Risk Factors for the Paediatric Patient: A Prospective Study Using Cotinine Levels in Children Undergoing Adenotonsillectomies

Background and Aims: Post-operative vomiting (POV) in children remains a significant clinical problem. This prospective study aims to investigate the applicability of well-established adult early post-operative nausea and vomiting (PONV) risk factors on paediatric POV after adenotonsillectomies under regulated anaesthetic conditions. Methods: After Institutional Review Board approval, 213 children aged 3–10-year-old were enrolled. The participants had pre-operative questionnaires completed, followed protocolised anaesthetic plans and had saliva analysed for cotinine. The primary outcomes were POV as correlated with age, gender, family or personal history of PONV, motion sickness history, opioid use, surgical time, anaesthetic time and environmental tobacco smoke (ETS) exposure, as assessed by cotinine levels and questionnaire reports. Data on analgesics, antiemetics and POV incidence before post-anaesthesia care unit discharge were collected. Statistical analysis was done through multiple logistic regression. Results: A total of 200 patients finalised the study. Early POV occurred in 32%. Family history of PONV (odds ratio [OR] = 5.3, P \u3c 0.01) and motion sickness history (OR = 4.4, P = 0.02) were highly significant risk factors. Age reached borderline statistical significance (OR = 1.4, P = 0.05). None of the other factors reached statistical significance. Conclusion: Early POV occurs frequently in paediatric patients undergoing adenotonsillectomies. In this paediatric-aged group, the incidence of POV was affected by the family history of PONV, and history of motion sickness. Age, female gender, opioid use, surgical and anaesthetic times did not affect the incidence of POV. ETS exposure, as assessed by cotinine levels and questionnaire reports, had no protective effect on early paediatric POV

TLR-3/9 agonists synergize with anti-ErbB2 mAb-Letter

Charlebois and colleagues recently reported that the antitumor activity of anti-ErbB2 mAb is enhanced by local polyI:C and CpG administration in murine breast tumor models (1) and concluded that this activity was dependent on IFNs, CD8+ T, and natural killer (NK) cells. The requirement for NK cells was based on in vivo depletion using anti-asialo-GM1 (ASGM1) Ab

Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate

Background Variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy. Methods Extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products. Results Cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; pConclusion The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels

BET inhibitors synergize with venetoclax to induce apoptosis in MYC-driven lymphomas with high BCL-2 expression

Although the MYC oncogenic network represents an attractive therapeutic target for lymphoma, MYC inhibitors have been difficult to develop. Alternatively, inhibitors of epigenetic/ transcriptional regulators, particularly the bromodomain and extraterminal (BET) family, have been used to modulate MYC. However, current benzodiazepine-derivative BET inhibitors (BETi) elicit disappointing responses and dose-limiting toxicity in relapsed/refractory lymphoma, potentially because of enrichment of high-risk molecular features and chemical backbone-associated toxicities. Consequently, novel nonbenzodiazepine BETi and improved mechanistic understanding are required. Here we characterize the responses of aggressive MYC-driven lymphomas to 2 nonbenzodiazepine BETi: PLX51107 and PLX2853. Both invoked BIM-dependent apoptosis and in vivo therapy, associated with miR-17∼92 repression, in murine Eµ-myc lymphomas, with PLX2853 exhibiting enhanced potency. Accordingly, exogenous BCL-2 expression abrogated these effects. Because high BCL-2 expression is common in diffuse large B-cell lymphoma (DLBCL), BETi were ineffective in driving apoptosis and in vivo therapy of DLBCL cell lines, mirroring clinical results. However, BETi-mediated BIM upregulation and miR-17∼92 repression remained intact. Consequently, coadministration of BETi and ABT199/venetoclax restored cell death and in vivo therapy. Collectively, these data identify BIM-dependent apoptosis as a critical mechanism of action for this class of BETi that, via coadministration of BH3 mimetics, can deliver effective tumor control in DLBCL.</p