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Intubation-associated trauma with the GlideScope is rare, but when it occurs, it is likely due to advancing the endotracheal tube (ETT) blindly between the direct view of the oropharynx and the video view of the glottis. It is also occasionally difficult to advance the ETT to the glottic aperture despite a good view of the glottis on the monitor. One technique to potentially address both issues is to introduce the ETT en bloc with the GlideScope, thus visualizing the ETT tip throughout its entire path. We hypothesized that this en bloc technique could be faster and potentially easier than the standard technique. Fifty patients with normal-appearing airways who required orotracheal intubation for elective surgery were randomly allocated to intubation with either the en bloc or the standard (GlideScope-first-then-ETT) technique. A three-dimensional printed clip was utilized to secure the ETT to the GlideScope during en bloc insertion. The primary outcome was time to intubation, defined from mask removal to first end-tidal carbon dioxide detection, recorded by a blinded observer. Secondary outcomes were subjective ease of intubation (100-mm visual analogue scale [VAS], 0 = easy; 100 = difficult), number of intubation attempts/failures, and incidence of oropharyngeal trauma (bleeding). The median [interquartile range (IQR)] intubation time was 36 [31–42] sec with the en bloc technique vs 41 [37–50] sec with the standard technique (difference in medians, 5 sec; 95% confidence interval [CI], 2 to 11; P = 0.008). The median [IQR] ease of intubation VAS was 11 [9–21] mm with the en bloc technique, and 15 [11–24] mm with the standard technique (difference in medians, 4 mm; 95% CI, −2 to 8; P = 0.19). Laryngoscopic grade and number of intubation attempts were similar between the groups; there was no oropharyngeal trauma noted. In this study of video laryngoscopy, intubation was slightly faster with the en bloc technique than with the standard GlideScope intubation technique, although the clinical importance of this difference is unknown. www.clinicaltrials.gov (NCT02787629); registered 1 June 2016.

Background Despite advances in immunosuppressive therapies, the rate of chronic transplant loss remains substantial. Organ injury involves various forms of cell death including apoptosis and necrosis. We now recognize that early injury of cardiac transplants involves a newly described form of programmed necrotic cell death, termed necroptosis. Because this involves receptor-interacting protein (RIP) kinase 1/3, this study aimed to establish the role of RIP3 in chronic cardiac allograft rejection. Methods We used major histocompatibility complex class II mismatched C57BL/6N (H-2; B6) or B6.RIP3 (H-2; RIP3) mice to B6.C-H-2 (H2-Ab1; bm12) mouse cardiac transplantation. Microvascular endothelial cells (MVEC) were developed from B6 and RIP3 cardiac grafts. Result CD4 T cell-mediated cardiac graft rejection is inhibited using RIP3 deficient donor grafts, with reduced cellular infiltration and vasculopathy compared with wild type cardiac grafts. Alloreactive CD4 T cell-mediated MVEC death involves TNFα, Fas ligand (FasL) and granzyme B. Although necroptosis and release of danger molecule high-mobility group box 1 are eliminated by the absence of RIP3, CD4 T cells had attenuated MVEC death through granzyme B and FasL. Conclusions CD4 T cell-mediated MVEC death involves in TNFα, FasL and granzyme B. Necroptotic cell death and release of the danger molecule may promote inflammatory responses and transplant rejection. Although loss of RIP3 does not eliminate alloimmune responses, chronic graft injury is reduced. RIP3 is an important therapeutic target but additional granzyme and caspases inhibition is required for sufficiently improving long-term graft survival.

Kidney transplant injury occurs with ischemia and alloimmunity. Members of the receptor interacting protein kinase family (RIPK1,3) are key regulators of "necroptosis," a newly recognized, regulated form of necrosis. Necroptosis and apoptosis death appear to be counterbalanced as caspase-8 inhibition can divert death from apoptosis to necrosis. Inhibition of necroptosis in donor organs to limit injury has not been studied in transplant models. In this study, necroptosis was triggered in caspase inhibited tubular epithelial cells (TEC) exposed to tumor necrosis factor alpha in vitro, while RIPK1 inhibition with necrostatin-1 or use of RIPK3(-/-) TEC, prevented necroptosis. In vivo, short hairpin RNA silencing of caspase-8 in donor B6 mouse kidneys increased necroptosis, enhanced high-mobility group box 1 release, reduced renal function and accelerated rejection when transplanted into BALB/c recipients. Using ethidium homodimer perfusion to assess necrosis in vivo, necrosis was abrogated in RIPK3(-/-) kidneys postischemia. Following transplantation, recipients receiving RIPK3(-/-) kidneys had longer survival (p = 0.002) and improved renal function (p = 0.03) when compared to controls. In summary, we show for the first time that RIPK3-mediated necroptosis in donor kidneys can promote inflammatory injury, and has a major impact on renal ischemia-reperfusion injury and transplant survival. We suggest inhibition of necroptosis in donor organs may similarly provide a major clinical benefit.

Non-coding RNA (ncRNA) comprises a substantial portion of primary transcripts that are generated by genomic transcription, but are not translated into protein. The possible functions of these once considered ‘junk’ molecules have incited considerable interest and new insights have emerged. The two major members of ncRNAs, namely micro RNA (miRNA) and long non-coding RNA (lncRNA), have important regulatory roles in gene expression and many important physiological processes, which has recently been extended to programmed cell death. The previous paradigm of programmed cell death only by apoptosis has recently expanded to include modalities of regulated necrosis (RN), and particularly necroptosis. However, most research efforts in this field have been on protein regulators, leaving the role of ncRNAs largely unexplored. In this review, we discuss important findings concerning miRNAs and lncRNAs that modulate apoptosis and RN pathways, as well as the miRNA–lncRNA interactions that affect cell death regulation.