Intubation Success in Critical Care Transport: A Multicenter Study.

INTRODUCTION: Tracheal intubation (TI) is a lifesaving critical care skill. Failed TI attempts, however, can harm patients. Critical care transport (CCT) teams function as the first point of critical care contact for patients being transported to tertiary medical centers for specialized surgical, medical, and trauma care. The Ground and Air Medical qUality in Transport (GAMUT) Quality Improvement Collaborative uses a quality metric database to track CCT quality metric performance, including TI. We sought to describe TI among GAMUT participants with the hypothesis that CCT would perform better than other prehospital TI reports and similarly to hospital TI success. METHODS: The GAMUT Database is a global, voluntary database for tracking consensus quality metric performance among CCT programs performing neonatal, pediatric, and adult transports. The TI-specific quality metrics are "first attempt TI success" and "definitive airway sans hypoxia/hypotension on first attempt (DASH-1A)." The 2015 GAMUT Database was queried and analysis included patient age, program type, and intubation success rate. Analysis included simple statistics and Pearson chi-square with Bonferroni-adjusted post hoc z tests (significance = p < 0.05 via two-sided testing). RESULTS: Overall, 85,704 patient contacts (neonatal n [%] = 12,664 [14.8%], pediatric n [%] = 28,992 [33.8%], adult n [%] = 44,048 [51.4%]) were included, with 4,036 (4.7%) TI attempts. First attempt TI success was lowest in neonates (59.3%, 617 attempts), better in pediatrics (81.7%, 519 attempts), and best in adults (87%, 2900 attempts), p < 0.001. Adult-focused CCT teams had higher overall first attempt TI success versus pediatric- and neonatal-focused teams (86.9% vs. 63.5%, p < 0.001) and also in pediatric first attempt TI success (86.5% vs. 75.3%, p < 0.001). DASH-1A rates were lower across all patient types (neonatal = 51.9%, pediatric = 74.3%, adult = 79.8%). CONCLUSIONS: CCT TI is not uncommon, and rates of TI and DASH-1A success are higher in adult patients and adult-focused CCT teams. TI success rates are higher in CCT than other prehospital settings, but lower than in-hospital success TI rates. Identifying factors influencing TI success among high performers should influence best practice strategies for TI.

Benchmarking Pain Assessment Rate in Critical Care Transport.

The purpose of this study is to determine the rate of pain assessment in pediatric neonatal critical care transport (PNCCT). The GAMUT database was interrogated for an 18-month period and excluded programs with less than 10% pediatric or neonatal patient contacts and less than 3 months of any metric data reporting during the study period. We hypothesized pain assessment during PNCCT is superior to prehospital pain assessment rates, although inferior to in-hospital rates. Sixty-two programs representing 104,445 patient contacts were analyzed. A total of 21,693 (20.8%) patients were reported to have a documented pain assessment. Subanalysis identified 17 of the 62 programs consistently reporting pain assessments. This group accounted for 24,599 patients and included 7,273 (29.6%) neonatal, 12,655 (51.5%) pediatric, and 4,664 (19.0%) adult patients. Among these programs, the benchmark rate of pain assessment was 90.0%. Our analysis shows a rate below emergency medical services and consistent with published hospital rates of pain assessment. Poor rates of tracking of this metric among participating programs was noted, suggesting an opportunity to investigate the barriers to documentation and reporting of pain assessments in PNCCT and a potential quality improvement initiative.

Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy.

Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-ß, desmin, α-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca(2+) response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas.

The exocyst protein Sec10 interacts with Polycystin-2 and knockdown causes PKD-phenotypes.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of renal cysts that destroy the kidney. Mutations in PKD1 and PKD2, encoding polycystins-1 and -2, cause ADPKD. Polycystins are thought to function in primary cilia, but it is not well understood how these and other proteins are targeted to cilia. Here, we provide the first genetic and biochemical link between polycystins and the exocyst, a highly-conserved eight-protein membrane trafficking complex. We show that knockdown of exocyst component Sec10 yields cellular phenotypes associated with ADPKD, including loss of flow-generated calcium increases, hyperproliferation, and abnormal activation of MAPK. Sec10 knockdown in zebrafish phenocopies many aspects of polycystin-2 knockdown-including curly tail up, left-right patterning defects, glomerular expansion, and MAPK activation-suggesting that the exocyst is required for pkd2 function in vivo. We observe a synergistic genetic interaction between zebrafish sec10 and pkd2 for many of these cilia-related phenotypes. Importantly, we demonstrate a biochemical interaction between Sec10 and the ciliary proteins polycystin-2, IFT88, and IFT20 and co-localization of the exocyst and polycystin-2 at the primary cilium. Our work supports a model in which the exocyst is required for the ciliary localization of polycystin-2, thus allowing for polycystin-2 function in cellular processes.