After controlling for potential confounders, this propensity-adjusted analysis demonstrates improved odds of FAS at intubation in the ICU with the use of an NMBA. This improvement in FAS is seen even with the use of a video laryngoscope.

Human pancreatic and prostate cancers metastasize along nerve axons during perineural invasion. The extracellular matrix laminin class of proteins is an abundant component of both myelinated and non-myelinated nerves. Analysis of human pancreatic and prostate tissue revealed both perineural and endoneural invasion with Schwann cells surrounded or disrupted by tumor, respectively. Tumor and nerve cell co-culture conditions were used to determine if myelinating or non-myelinating Schwann cell (S16 and S16Y, respectively) phenotype was equally likely to promote integrin-dependent cancer cell invasion and migration on laminin. Conditioned medium from S16 cells increased tumor cell (DU145, PC3, and CFPAC1) invasion into laminin approximately 1.3–2.0 fold compared to fetal bovine serum (FBS) treated cells. Integrin function (e.g., ITGA6p formation) increased up to 1.5 fold in prostate (DU145, PC3, RWPE-1) and pancreatic (CFPAC1) cells, and invasion was dependent on ITGA6p formation and ITGB1 as determined by function-blocking antibodies. In contrast, conditioned medium isolated from S16Y cells (non-myelinating phenotype) decreased constitutive levels of ITGA6p in the tumor cells by 50% compared to untreated cells and decreased ITGA6p formation 3.0 fold compared to S16 treated cells. Flow cytometry and western blot analysis revealed loss of ITGA6p formation as reversible and independent of overall loss of ITGA6 expression. These results suggest that the myelinating phenotype of Schwann cells within the tumor microenvironment increased integrin-dependent tumor invasion on laminin.

In this single-center study, presence of blood in the airway, airway edema, cervical immobility, and obesity are associated with higher odds of first-attempt failure, when intubation was performed with video laryngoscopy in an ICU.

The laminin binding integrin α6β1 plays a major role in determining the aggressive phenotype of tumor cells during metastasis. Our previous work has shown that cleavage of the α6β1 integrin to produce the structural variant α6pβ1 on tumor cell surfaces is mediated by the serine protease uPA. Cleavage of α6β1 increases tumor cell motility, invasion, and prostate cancer metastasis, and blockage of uPA inhibits α6pβ1 production. In human tumors uPA and uPAR are expressed in tumor cells and tumor associated macrophages (TAMs). TAMs localize to solid tumors and contribute to increased tumor growth and the metastatic phenotype. In our present study, we utilized a co-culture system of PC-3 prostate tumor cells and macrophages (12-O-tetradecanoylphorbol-13-acetate (TPA) differentiated human leukemia HL-60 cells) to investigate the hypothesis that macrophages stimulate the production of the pro-metastatic variant α6pβ1 on human prostate cancer cells via the uPA/uPAR axis. Our results indicate that adherent macrophages co-cultured with PC-3 cells increased PC-3 uPAR mRNA, uPAR cell-surface protein expression and α6 integrin cleavage. The stimulation does not require macrophage/tumor cell contact since macrophage conditioned medium is sufficient for increased uPAR transcription and α6 cleavage dependent PC-3 cell invasion. The increased cleavage was dependent on uPAR since production was blocked by silencing RNA targeting uPAR. These results indicate that macrophages can stimulate uPA/uPAR production in tumor cells which results in α6 integrin cleavage. These data suggest that tumor associated macrophages promote pro metastatic integrin dependent pericellular proteolysis.

The purpose of this investigation was to investigate the association between first attempt success and intubation-related complications in the Intensive Care Unit after the widespread adoption of video laryngoscopy. We further sought to characterize and identify the predictors of complications that occur despite first attempt success. This was a prospective observational study of consecutive intubations performed with video laryngoscopy at an academic medical Intensive Care Unit. Operator, procedural, and complication data were collected. Multivariable logistic regression was used to examine the relationship between the intubation attempts and the occurrence of one or more complications. A total of 905 patients were intubated using a video laryngoscope. First attempt success occurred in 739 (81.7 %), whereas >1 attempt was needed in 166 (18.3 %). One or more complications occurred in 146 (19.8 %) of those intubated on the first attempt versus 107 (64.5 %, p < 0.001) of those requiring more than one attempt. Logistic regression analysis shows that >1 attempt is associated with 6.4 (95 % CI 4.4-9.3) times the adjusted odds of at least one complication. Pre-intubation predictors of at least one complication despite first attempt success include vomit or edema in the airway as well as the presence of hypoxemia or hypotension. There are increased odds of complications with even a second attempt at intubation in the Intensive Care Unit. Complications occur frequently despite a successful first attempt, and as such, the goal of airway management should not be simply first attempt success, but instead first attempt success without complications.