Treatment in the pediatric emergency department is evidence based: a retrospective analysis

Background  

Our goal was to quantify the evidence that is available to the physicians of a pediatric emergency department (PED) in making treatment decisions. Further, we wished to ascertain what percentage of evidence for treatment provided in the PED comes from pediatric studies.     

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.     

SARS-CoV-2 Infections in Vaccinated and Unvaccinated Populations in Camp Lemonnier,Djibouti, from April 2020 to January 2022

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the disparity between developed and developing countries for infectious disease surveillance and the sequencing of pathogen genomes. The majority of SARS-CoV-2 sequences published are from Europe, North America, and Asia. Between April 2020 and January 2022, 795 SARS-CoV-2-positive nares swabs from individuals in the U.S. Navy installation Camp Lemonnier, Djibouti, were collected, sequenced, and analyzed. In this study, we described the results of genomic sequencing and analysis for 589 samples, the first published viral sequences for Djibouti, including 196 cases of vaccine breakthrough infections. This study contributes to the knowledge base of circulating SARS-CoV-2 lineages in the under-sampled country of Djibouti, where only 716 total genome sequences are available at time of publication. Our analysis resulted in the detection of circulating variants of concern, mutations of interest in lineages in which those mutations are not common, and emerging spike mutations.     

Prospective analysis of a surgical algorithm to achieve ventilator weaning in cervical tetraplegia

Objectives: Chronic ventilator dependency in cervical tetraplegia is associated with substantial morbidity. When non-invasive weaning methods have failed the primary surgical treatment is diaphragm pacing. Phrenic nerve integrity and diaphragm motor units are requirements for effective pacing but may need to be restored for successful weaning. A surgical algorithm that includes: 1. Diaphragm pacing, 2. Phrenic nerve reconstruction, and 3. Diaphragm muscle replacement, may provide the capability of reducing or reversing ventilator dependency in virtually all cervical tetraplegics.Design: Prospective case series.Setting: A university-based hospital from 2015 to 2019.Participants: Ten patients with ventilator-dependent cervical tetraplegia.Interventions: I. Pacemaker alone, II. Pacemaker + phrenic nerve reconstruction, or III. Pacemaker + diaphragm muscle replacement.Outcome measures: Time from surgery to observed reduction in ventilator requirements (↓VR), ventilatory needs as of most recent follow-up [no change (NC), partial weaning (PW, 1–12 h/day), or complete weaning (CW, >12 h/day)], and complications.Results: Both patients in Group I achieved CW at 6-month follow-up. Two patients in Group II achieved CW, and in another two patients PW was achieved, at 1.5–2-year follow-up. The remaining two patients are NC at 6 and 8-month follow-up, respectively. In group III, both patients achieved PW at 2-year follow-up. Complications included mucous plugging (n = 1) and pacemaker malfunction requiring revision (n = 3).Conclusion: Although more investigation is necessary, phrenic nerve reconstruction or diaphragm muscle replacement performed (when indicated) with pacemaker implantation may allow virtually all ventilator-dependent cervical tetraplegics to partially or completely wean.     

Erratum to “Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: Substantiating test strategies with data from routine studies” [Regul. Toxicol. Pharmacol. (2012) 402–414]

Skin corrosion or irritation refers to the production of irreversible or reversible damage to the skin following the application of a test substance, respectively. Traditionally, hazard assessments are conducted using the in vivo Draize skin test, but recently in vitro tests using reconstructed human epidermis (RhE) models have gained regulatory acceptance. In this study, skin corrosion (SCT) and irritation tests (SIT) using a RhE model were implemented to reduce the number of in vivo tests required by regulatory bodies. One hundred and thirty-four materials were tested from a wide range of substance classes included 46 agrochemical formulations. Results were assessed according to UN GHS, EU-CLP, ANVISA and US EPA classification schemes. There was high correlation between the two in vitro tests. Assessment of the SCT sensitivity was not possible due to the limited number of corrosives in the data set; SCT specificity and accuracy were 89% for all classification systems. Accuracy (63–76%) and sensitivity (53–67%) were low in the SIT. Specificity and concordance for agrochemical formulations alone in both the SCT and SIT were comparable to the values for the complete data set (SCT: 91% vs. 89% specificity, 91% vs. 89% accuracy and SIT: 64–88% vs. 70–85% specificity, 56–75% vs. 63–76% accuracy).