Simultaneous en bloc endotracheal tube insertion with GlideScope® Titanium™ video laryngoscope use: a randomized-controlled trial.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02787629); registered 1 June 2016.

RéSUMé: OBJECTIF: Les traumatismes associés à l'intubation avec un GlideScope sont rares; quand ils surviennent, ils sont souvent provoqués par l'insertion du tube endotrachéal (TET) en aveugle entre la visualisation directe de l'oropharynx et la visualisation par vidéo de la glotte. Il arrive parfois qu'il soit difficile d'insérer le TET dans l'ouverture glottique malgré une bonne visualisation de la glotte sur le moniteur. Une technique permettant potentiellement de résoudre ces deux problèmes est l'introduction 'en bloc' du TET et du GlideScope, de manière à obtenir une vue de l'extrémité du TET tout au long de son parcours. Nous avons émis l'hypothèse que cette technique en bloc pourrait être à la fois plus rapide et potentiellement plus facile à réaliser que la technique standard. MéTHODE: Cinquante patients présentant des voies aériennes d'apparence normale et nécessitant une intubation orotrachéale pour une chirurgie non urgente ont été randomisés à être intubés soit par une technique en bloc, soit en utilisant la technique standard (GlideScope puis TET). Une pince imprimée en 3D a été utilisée pour attacher le TET au GlideScope pendant l'insertion en bloc. Le critère d'évaluation principal était le temps nécessaire à l'intubation, défini à partir du moment de retrait du masque jusqu'à la première détection de dioxyde de carbone télé-expiratoire, tel que mesuré par un observateur en aveugle. Les critères secondaires comprenaient la facilité subjective d'intubation (sur une échelle visuelle analogique [EVA] de 100 mm, où 0 = facile et 100 = difficile), le nombre de tentatives et d'échecs d'intubation, et l'incidence de lésions oropharyngées (saignement). RéSULTATS: Le temps d'intubation médian [écart interquartile (ÉIQ)] était de 36 [31­42] sec avec la technique en bloc vs 41 [37­50] sec avec la technique standard (différence de moyennes, 5 sec; intervalle de confiance [IC] 95 %, 2 à 11; P = 0,008). La facilité d'intubation médiane [ÉIQ] sur l'EVA était de 11 [9-21] mm avec la technique en bloc, et 15 [11-24] mm avec la technique standard (différence de moyennes, 4 mm; IC 95 %, -2 à 8; P = 0,19). La classification de la laryngoscopie et le nombre de tentatives d'intubation étaient similaires dans les deux groupes; aucun traumatisme oropharyngé n'a été enregistré. CONCLUSION: Dans cette étude vidéolaryngoscopique, l'intubation était légèrement plus rapide lors de l'utilisation de la technique en bloc que lors d'une technique d'intubation standard avec le GlideScope, bien que l'importance clinique de cette différence soit inconnue. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02787629); enregistrée le 1er juin 2016.

Validation of an effective, low cost, Free/open access 3D-printed stethoscope.

The modern acoustic stethoscope is a useful clinical tool used to detect subtle, pathological changes in cardiac, pulmonary and vascular sounds. Currently, brand-name stethoscopes are expensive despite limited innovations in design or fabrication in recent decades. Consequently, the high cost of high quality, brand name models serves as a barrier to clinicians practicing in various settings, especially in low- and middle-income countries. In this publication, we describe the design and validation of a low-cost open-access (Free/Libre) 3D-printed stethoscope which is comparable to the Littmann Cardiology III for use in low-access clinics.

Intracellular pH Regulates TRAIL-Induced Apoptosis and Necroptosis in Endothelial Cells.

During ischemia or inflammation of organs, intracellular pH can decrease if acid production exceeds buffering capacity. Thus, the microenvironment can expose parenchymal cells to a reduced extracellular pH which can alter pH-dependent intracellular functions. We have previously shown that while silencing caspase-8 in an in vivo ischemia reperfusion injury (IRI) model results in improved organ function and survival, removal of caspase-8 function in a donor organ can paradoxically result in enhanced receptor-interacting protein kinase 1/3- (RIPK1/3-) regulated necroptosis and accelerated graft loss following transplantation. In our current study, TRAIL- (TNF-related apoptosis-inducing ligand-) induced cell death in vitro at neutral pH and caspase-8 inhibition-enhanced RIPK1-dependent necroptotic death were confirmed. In contrast, both caspase-8 inhibition and RIPK1 inhibition attenuated cell death at a cell pH of 6.7. Cell death was attenuated with mixed lineage kinase domain-like (MLKL) silencing, indicating that MLKL membrane rupture, a distinctive feature of necroptosis, occurs regardless of pH. In summary, there is a distinct regulatory control of apoptosis and necroptosis in endothelial cells at different intracellular pH. These results highlight the complexity of modulating cell death and therapeutic strategies that may need to consider different consequences on cell death dependent on the model.

Necroptosis Is Involved in CD4+ T Cell-Mediated Microvascular Endothelial Cell Death and Chronic Cardiac Allograft Rejection.

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.

Regulatory non-coding RNA: new instruments in the orchestration of cell death.

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.