Use of the intubating laryngeal mask airway in the emergency department: A ten-year retrospective review.

BACKGROUND: Extraglottic devices, such as the intubating laryngeal mask airway (ILMA), facilitate ventilation and oxygenation and are useful for emergency airway management, especially as rescue devices. In the operating room setting the ILMA has been highly successful. However, its performance in the ED has not been described. We sought to describe the indications for and success of the ILMA when used in the ED. METHODS: We performed retrospective, observational study of patients who had an LMA® Fastrach™ (hereafter termed ILMA) placed in a single ED between 2007 and 2017. Patients were identified by keyword search of ED notes in the electronic medical record. Trained abstractors reviewed charts and videos to determine patient characteristics, indication for ILMA placement, success of oxygenation and ventilation, intubation methods and success, and complications related to the device. RESULTS: During the study period 218 patients had an ILMA placed in the ED. The ILMA was used as a primary device in 118 patients (54%), and as a rescue device in 100 patients (46%). The median number of ILMA uses per faculty physician during the study period was 3. The ILMA oxygenated and ventilated successfully in 212 instances (98%), including 96 times (96%) when used as a rescue airway. Failure of oxygenation was due to tracheal injury (2), abnormal laryngeal inlet anatomy (2), or poor operator technique (1). Intubation through the ILMA was successful in 159 of 192 patients (83%), including a success rate of 81% (112 of 139 patients) with blind intubation. CONCLUSION: The ILMA was highly successful in oxygenation, with reasonable intubation success, even when used infrequently by emergency physicians. The ILMA should be considered a valuable primary and rescue intubation device in the ED.

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma.

BACKGROUND: Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease. METHODS: This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program. Associations between clinical factors and metastasis at diagnosis were estimated using logistic regression models. RESULTS: In humans, those with trunk tumors had higher odds of metastasis at diagnosis compared to those with lower limb tumors (OR = 2.38, 95% CI: 1.51, 3.69). A similar observation was seen in dogs with trunk tumors compared to dogs with forelimb tumors (OR = 3.28, 95% CI 1.36, 7.50). Other associations were observed in humans but not in dogs. Humans aged 20-29 years had lower odds of metastasis at diagnosis compared to those aged 10-14 years (OR = 0.67, 95% CI: 0.47, 0.96); every 1-cm increase in tumor size was associated with a 6% increase in the odds of metastasis at diagnosis (95% CI: 1.04, 1.08); compared to those with a white, non-Hispanic race, higher odds were observed among those with a black, non-Hispanic race (OR: 1.51, 95% CI: 1.04, 2.16), and those with a Hispanic origin (OR 1.35, 95% CI: 1.00, 1.81). CONCLUSION: A common mechanism may be driving trunk tumors to progress to detectable metastasis prior to diagnosis in both species.

Identification of candidate neoantigens produced by fusion transcripts in human osteosarcomas.

Osteosarcomas are characterized by highly disrupted genomes. Although osteosarcomas lack common fusions, we find evidence of many tumour specific gene-gene fusion transcripts, likely due to chromosomal rearrangements and expression of transcription-induced chimeras. Most of the fusions result in out-of-frame transcripts, potentially capable of producing long novel protein sequences and a plethora of neoantigens. To identify fusions, we explored RNA-sequencing data to obtain detailed knowledge of transcribed fusions, by creating a novel program to compare fusions identified by deFuse to de novo transcripts generated by Trinity. This allowed us to confirm the deFuse results and identify unusual splicing patterns associated with fusion events. Using various existing tools combined with this custom program, we developed a pipeline for the identification of fusion transcripts applicable as targets for immunotherapy. In addition to identifying candidate neoantigens associated with fusions, we were able to use the pipeline to establish a method for measuring the frequency of fusion events, which correlated to patient outcome, as well as highlight some similarities between canine and human osteosarcomas. The results of this study of osteosarcomas underscores the numerous benefits associated with conducting a thorough analysis of fusion events within cancer samples.

Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma.

Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2. Proliferation, migration, and anchorage independent growth were evaluated. RNA sequencing and immunohistochemistry of human osteosarcoma tissue samples were used to further evaluate the potential role of the Slit-Robo pathway in osteosarcoma. The effects of Srgap2 expression modulation in the murine OS cell lines support the hypothesis that SRGAP2 may have a role as a suppressor of metastases in osteosarcoma. Additionally, SRGAP2 and other genes in the Slit-Robo pathway have altered transcript levels in a subset of mouse and human osteosarcoma, and SRGAP2 protein expression is reduced or absent in a subset of primary tumor samples. SRGAP2 and other axon guidance proteins likely play a role in osteosarcoma metastasis, with loss of SRGAP2 potentially contributing to a more aggressive phenotype.

Prevalence of Metastasis at Diagnosis of Osteosarcoma: An International Comparison.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in many countries, with metastatic disease responsible for most patient deaths. This study compares the prevalence of metastatic OS at diagnosis across countries to inform the critical question of whether diagnostic delay or tumor biology drives metastases development prior to diagnosis. PROCEDURE: A literature search of the PubMed database was conducted to compare the prevalence of metastatic disease at the time of OS diagnosis between countries. A pooled prevalence with 95% confidence intervals was calculated for each study meeting inclusion criteria. Studies were grouped for analysis based on human development index (HDI) scores. RESULTS: Our analysis found an 18% (95% confidence interval [CI]: 15%, 20%) average global pooled proportion of metastasis at OS diagnosis. The average prevalence of metastasis at diagnosis increased as HDI groupings decreased, with very high HDI, high HDI, and medium/low HDI groups found to be 15% (95% CI: 13%, 17%), 20% (95% CI: 14%, 28%), and 31% (95% CI: 15%, 52%), respectively. CONCLUSIONS: Our evidence suggests there is a biological baseline for metastatic OS at diagnosis, which is observed in countries with very high HDI. In countries with medium/low HDI, where there are more barriers to accessing healthcare, the higher prevalence of metastasis may result from treatment delay or an artificial prevalence inflation due to patients with less severe symptoms not presenting to clinic. Additional research in countries with medium/low HDI may reveal that earlier detection and treatment could improve patient outcomes in those countries.