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BACKGROUND: The supraglottic airway device (SGD) was introduced as a breakthrough in airway management. The Fastrach emerged as the first commercially available intubating SGD, drawing extensive investigation. I-gel is a more recent device that has gained popularity, can be used as an intubating SGD, and replaced Fastrach in many institutions. However, there is uncertainty regarding the comparison between these devices in terms of efficacy for intubation and ventilation, and safety in an airway rescue situation. METHODS: PubMed, EMBASE, Scopus, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing I-gel and Fastrach SGD in adult patients undergoing intubation. The primary outcome was the first-pass success rate for tracheal intubation. Secondary outcomes were tracheal intubation time, SGD insertion time and success, and complications. We computed risk ratios (RRs) to assess binary end points and weighted mean differences (WMDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome and its subgroup analysis (P < .05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P < .01 was considered statistically significant). RESULTS: This study included a total of 14 RCTs encompassing 1340 patients. The results indicated a significant difference in the first-pass success rate favoring Fastrach (RR, 0.81; 95% CI, 0.67-0.98; P = .03; I² = 91%). In the subgroup analysis, when a flexible scope was utilized through I-gel, providers achieved a better tracheal intubation first-pass success rate (RR, 1.05; 95% CI, 1.01-1.11; P = .03; I² = 0%), compared with the Fastrach. Overall intubation success rates (RR, 0.92; 99% CI, 0.82-1.04; P = .08, I² = 92%) and time (WMD - 1.03 seconds; 99% CI, -4.75 to 2.69; P = .48; I² = 84%) showed no significant difference irrespective of the device used. There was no significant difference regarding device insertion time by the providers (WMD -6.48 seconds; 99% CI, -13.23 to 0.27; P = .01; I2 = 98%). Success rates of the providers' initial SGD insertion and complications such as sore throat (RR, 1.01; 99% CI, 0.65-1.57; P = .95, I² = 33%) and blood presence post-SGD removal (RR, 0.89; 99% CI, 0.42-1.86; P = .68, I² = 0%) showed no significant difference. CONCLUSIONS: Based on our findings, a higher first-pass success rate was observed with the use of Fastrach when compared to I-gel. However, the use of I-gel might result in a better intubation success rate with the flexible scope-guided intubation. There are no significant differences in performance in terms of the success rate for intubation overall, time for device insertion, or time to intubation or complications regardless of the device used.

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PURPOSE: The difficult airway cart is essential for difficult airway management. Recognition of the importance of human factors in critical scenarios promoted the evolution of the difficult airway cart. Limitation to essential equipment, a structured layout, and proper labelling should be observed. We sought to redesign the difficult airway cart accordingly and analyze how perioperative professionals reacted to it. METHODS: We conducted a two-phase prospective qualitative improvement project involving a multidisciplinary team. In phase 1, we reconfigured our difficult airway cart, including developing icons for labelling the drawers and discussing the equipment content. In phase 2, we delivered a multidisciplinary educational program and pre- and postsession questionnaires were administered to the professionals involved and compared. RESULTS: Phase 1 of the project encompassed 21 participants. We presented the final layout and content of the difficult airway cart. In phase 2, 44 participants responded the presession questionnaires, and 30 participants answered the postsession questionnaires. The results showed that the new design and the implementation program increased the comfort level of professionals involved in a potential airway crisis (presession mean [standard deviation (SD)]: anesthesiologists, 8.0 [1.9]; anesthesia assistants/respiratory therapists [AAs/RTs], 9.3 [0.8]; operating room registered nurses [OR RNs], 6.3 [2.7]; P = 0.001; postsession: anesthesiologists, 8.5 [2.0]; AAs/RTs, 9.6 [0.5]; OR RN, 7.9 [2.0]; P = 0.10). Nevertheless, the improvement was only statistically significant among the OR RNs (presession mean [SD]: 6.3 [2.7]; postsession: 7.9 [2.0]; P = 0.01). Additionally, the program facilitated the recognition of the location of airway equipment in the airway cart (positive responses ranging from 97% to 100%). CONCLUSION: Our quality improvement project successfully designed and implemented a new visual-based difficult airway cart at our institution. We believe this report enables other institutions to reproduce our project.

RéSUMé: OBJECTIF: Le chariot d'intubation difficile est essentiel pour la prise en charge des voies aériennes difficiles. La reconnaissance de l'importance des facteurs humains dans les situations critiques a favorisé l'évolution du chariot d'intubation difficile. Il est crucial de se limiter à l'équipement essentiel tout en organisant les éléments de manière structurée et en les étiquetant adéquatement. Nous avons cherché à repenser le chariot d'intubation difficile en gardant ces éléments à l'esprit et à analyser la réaction des professionnel·les oeuvrant en périopératoire. MéTHODE: Nous avons réalisé un projet d'amélioration qualitative prospective en deux phases impliquant une équipe multidisciplinaire. Au cours de la phase 1, nous avons reconfiguré notre chariot d'intubation difficile, en développant notamment des icônes pour étiqueter les tiroirs et en discutant du contenu matériel. Au cours de la phase 2, nous avons mis en place un programme éducatif multidisciplinaire et des questionnaires ont été administrés aux professionnel·les concerné·es avant et après la session. RéSULTATS: La phase 1 du projet a réuni 21 participant·es. Nous avons présenté la disposition finale et le contenu du chariot d'intubation difficile. Au cours de la phase 2, 44 participant·es ont répondu aux questionnaires d'avant-session et 30 participant·es ont répondu aux questionnaires d'après-session. Les résultats ont montré que la nouvelle disposition avec icônes et le programme de mise en œuvre ont augmenté le niveau de confort des professionnel·les impliqué·es dans une situation critique potentielle impliquant les voies aériennes (moyenne avant la séance [écart type (ET)] : anesthésiologistes, 8,0 [1,9]; assistant·es en anesthésie/inhalothérapeutes, 9,3 [0,8]; personnel infirmier autorisé en salle d'opération (SOP), 6,3 [2,7]; P = 0,001; après la session : anesthésiologistes, 8,5 [2,0]; assistant·es en anesthésie/inhalothérapeutes, 9,6 [0,5]; personnel infirmier de SOP, 7,9 [2,0]; P = 0,10). Néanmoins, l'amélioration n'était statistiquement significative que chez le personnel infirmier autorisé de SOP (moyenne avant la session [ET] : 6,3 [2,7]; après la session : 7,9 [2,0]; P = 0,01). De plus, le programme a facilité la reconnaissance de l'emplacement de l'équipement pour les voies aériennes dans le chariot d'intubation (réponses positives allant de 97 % à 100 %). CONCLUSION: Dans le cadre de notre projet d'amélioration de la qualité, nous avons réussi à concevoir et mettre en œuvre un nouveau chariot d'intubation difficile avec icônes dans notre établissement. Nous pensons que ce compte rendu permettra à d'autres institutions de reproduire notre projet.

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Introduction: Next-generation sequencing (NGS) is currently widely used for biomarker studies and molecular profiling to identify concurrent alterations that can lead to the better characterization of a tumor's molecular landscape. However, further evaluation of technical aspects related to the detection of gene rearrangements and copy number alterations is warranted. Methods: There were 12 ALK rearrangement-positive tumor specimens from patients with non-small cell lung cancer (NSCLC) previously detected via fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and an RNA-based NGS assay, and 26 MET high gene copy number (GCN) cases detected by FISH, selected for this retrospective study. All 38 pre-characterized cases were reassessed utilizing the PGDx™ elio™ tissue complete assay, a 505 gene targeted NGS panel, to evaluate concordance with these conventional diagnostic techniques. Results: The detection of ALK rearrangements using the DNA-based NGS assay demonstrated excellent sensitivity with the added benefit of characterizing gene fusion partners and genomic breakpoints. MET copy number alterations were also detected; however, some discordances were observed likely attributed to differences in algorithm, reporting thresholds and gene copy number state. TMB was also assessed by the assay and correlated to the presence of NSCLC driver alterations and was found to be significantly lower in cases with NGS-confirmed canonical driver mutations compared with those without (p=0.0019). Discussion: Overall, this study validates NGS as an accurate approach for detecting structural variants while also highlighting the need for further optimization to enable harmonization across methodologies for amplifications.

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BACKGROUND: The high-fidelity ORSIM (Airway Simulation Ltd) and the low-fidelity wooden-block fiber-optic task trainers allow users to familiarize themselves with the psychomotor skills required to manipulate the fiber-optic scope. METHODS: This single-center study aimed to compare residents' performance of fiber-optic intubation after 2 different types of task training. Twenty-four residents with experience of <8 fiber-optic intubations were randomized to either the ORSIM or a wooden-block task trainer. In a single teaching session, the resident performed 20 fiber-optic intubations on their assigned task trainer. This implied simulator competence. In the 4 months after this training, all subjects then attempted to perform a fiber-optic intubation on an American Society of Anesthesiologists (ASA) I or II anesthetized patient whose airway was preoperatively assessed as normal. The primary outcome was the cumulative sum (CUSUM) learning curves obtained as the residents trained on their respective task trainers. Secondary outcomes included: the mean time (in seconds) to perform each of the 20 fiber-optic intubations on their assigned task trainer, the total simulator training time, global rating scale score, checklist score, and time to carina when performing fiber-optic intubation on the patient. RESULTS: The CUSUM analysis showed that the ORSIM group achieved simulator competence faster. The mean time to perform fiber-optic intubation was shorter in the ORSIM group. A 2-way analysis of variance (ANOVA) test suggests that the combined effect of group (wooden-block or ORSIM) and time is statistically significant ( P < .05).Total training time (mean, 899 s ± 440 s vs 1358 s ± 405 s; 95% confidence interval [CI], 100.46-818.54; P = .01) was also significantly better in the ORSIM group.No significant difference was found between the 2 groups ( P > 0) in terms of global rating scale, checklist score, and time to reach the carina ( P >.05) when performing the fiber-optic intubation on the patient. CONCLUSIONS: ORSIM showed superiority in terms of the CUSUM learning curve in reaching competence faster in fewer attempts. There was no statistically significant difference in residents' performance when translated to clinical practice on a patient. This information should assist course directors when choosing task trainers for fiber-optic intubation training programs.

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PURPOSE: A large vertical incision is recommended when performing front-of-neck access in patients with impalpable neck landmarks during a cannot intubate-cannot oxygenate (CICO) scenario. We investigated the impact of ultrasonography on vertical incision size of a front-of-neck access on an ultrasound-compatible impalpable porcine larynx model. METHODS: Emergency medicine and anesthesia trainees were randomized to the Ultrasound (US, n = 21) and Non-Ultrasound (NUS, n = 21) groups. Within 1 week after a teaching session on airway ultrasound and Scalpel-Bougie-Tube (SBT) technique, participants were instructed to perform cricothyroidotomy on the model during a simulated cannot intubate-cannot oxygenate scenario. The primary outcome was a vertical size incision. Secondary outcomes were procedural completion time, horizontal size incision, tissue injury severity, and correct tube placement. RESULTS: The ultrasound group performed a significantly smaller vertical incision [median (IQR), 35.0 (15, 40) vs 65.0 (52, 100) mm (95% CI) - 30.0 (- 55.1, - 4.9), p = 0.02] and took longer total time to complete the procedure [median (IQR), 200.5 (126, 267) vs 93.5 (71.0, 167.5) secs (95% CI) 91.0 (3.73, 178.3), p = 0.04]. Tissue injury severity and correct tube placement were similar between groups. CONCLUSIONS: Ultrasound-guided identification of the cricothyroid membrane significantly reduced the recommended vertical incision size with similar success rates. However, there was an increased time when performing a Scalpel-Bougie-Tube cricothyroidotomy on an impalpable porcine larynx model by physicians in training. Ultrasonography should not be used in an emergency scenario of airway rescue. Its potential use to pre-mark the cricothyroid membrane should be considered in difficult airway management of impalpable neck.

RéSUMé: OBJECTIF: Il est recommandé de pratiquer une grande incision verticale lors de l'accès à l'avant du cou chez les patients dont les repères du cou sont impalpables, dans le cadre d'un scénario d'intubation impossible à oxygéner (CICO). Nous avons étudié l'impact de l'échographie sur la taille de l'incision verticale d'un accès à la face avant du cou sur un modèle de larynx porcin impalpable compatible avec l'échographie. MéTHODES: Des stagiaires en médecine d'urgence et en anesthésie ont été répartis de manière aléatoire entre les groupes "échographie" (US, n = 21) et "non-échographie" (NUS, n = 21). Une semaine après une session d'enseignement sur l'échographie des voies aériennes et la technique Scalpel-Bougie-Tube (SBT), les participants ont reçu l'instruction de réaliser une cricothyroïdotomie sur le modèle lors d'un scénario simulé d'impossibilité d'intubation et d'oxygénation. Le résultat primaire était une incision de taille verticale. Les résultats secondaires étaient le temps de réalisation de la procédure, la taille horizontale de l'incision, la gravité de la lésion tissulaire et le placement correct du tube. RéSULTATS: Le groupe échographie a réalisé une incision verticale significativement plus petite [médiane (IQR), 35,0 (15,40) vs 65,0 (52,100) mm (IC à 95 %) -30,0 (-55,1, -4,9), p = 0,02] et a pris un temps total plus long pour terminer la procédure [médiane (IQR), 200,5 (126, 267) vs 93,5 (71,0, 167,5) secondes (IC à 95 %) 91,0 (3,73, 178,3), p = 0,04]. La gravité des lésions tissulaires et le placement correct du tube étaient similaires entre les groupes. CONCLUSIONS: L'identification échoguidée de la membrane cricothyroïdienne a réduit de manière significative la taille de l'incision verticale recommandée avec des taux de réussite similaires. Cependant, il y avait une augmentation du temps lors de la réalisation d'une cricothyroïdotomie Scalpel-Bougie-Tube sur un modèle de larynx porcin impalpable par des médecins en formation. L'échographie ne doit pas être utilisée dans un scénario d'urgence de sauvetage des voies respiratoires. Son utilisation potentielle pour pré-marquer la membrane cricothyroïdienne devrait être envisagée dans la gestion des voies aériennes difficiles du cou impalpable.

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BACKGROUND: Decision-making deficits in airway emergencies have led to adverse patient outcomes. A cognitive aid would assist clinicians through critical decision-making steps, preventing key action omission. OBJECTIVE: We aimed to investigate the effects of a visual airway cognitive aid on decision-making in a simulated airway emergency scenario. DESIGN: Randomised controlled study. SETTING: Single-institution, tertiary-level hospital in Toronto, Canada from September 2017 to March 2019. PARTICIPANTS: Teams consisting of a participant anaesthesia resident, nurse and respiratory therapist were randomised to intervention (N = 20 teams) and control groups (N = 20 teams). INTERVENTION: Participants in both groups received a 15-min didactic session on crisis resource management which included teamwork communication and the concepts of cognitive aids for the management of nonairway and airway critical events. Only participants in the intervention group were familiarised, oriented and instructed on a visual airway cognitive aid that was developed for this study. Within 1 to 4 weeks after the teaching session, teams were video-recorded managing a simulated 'cannot intubate-cannot oxygenate' scenario with the aid displayed in the simulation centre. MAIN OUTCOME MEASURES: Decision-making time to perform a front-of-neck access (FONA), airway checklist actions, teamwork performances and a postscenario questionnaire. RESULTS: Both groups performed similar key airway actions; however, the intervention group took a shorter decision-making time than the control group to perform a FONA after a last action [mean ± SD, 80.9 ±â€Š54.5 vs. 122.2 ±â€Š55.7 s; difference (95% CI) -41.2 (-76.5 to -6.0) s, P = 0.023]. Furthermore, the intervention group used the aid more than the control group (63.0 vs. 28.1%, P < 0.001). Total time of scenario completion, action checklist and teamwork performances scores were similar between groups. CONCLUSIONS: Prior exposure and teaching of a visual airway cognitive aid improved decision-making time to perform a FONA during a simulated airway emergency.

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Biofilm-associated polymicrobial infections tend to be challenging to treat. Candida albicans and Staphylococcus aureus are leading pathogens due to their ability to form biofilms on medical devices. However, the therapeutic implications of their interactions in a host is largely unexplored. In this study, we used a mouse subcutaneous catheter model for in vivo-grown polymicrobial biofilms to validate our in vitro findings on C. albicans-mediated enhanced S. aureus tolerance to vancomycin in vivo. Comparative assessment of S. aureus recovery from catheters with single- or mixed-species infection demonstrated failure of vancomycin against S. aureus in mice with co-infected catheters. To provide some mechanistic insights, RNA-seq analysis was performed on catheter biofilms to delineate transcriptional modulations during polymicrobial infections. C. albicans induced the activation of the S. aureus biofilm formation network via down-regulation of the lrg operon, repressor of autolysis, and up-regulation of the ica operon and production of polysaccharide intercellular adhesin (PIA), indicating an increase in eDNA production, and extracellular polysaccharide matrix, respectively. Interestingly, virulence factors important for disseminated infections, and superantigen-like proteins were down-regulated during mixed-species infection, whereas capsular polysaccharide genes were up-regulated, signifying a strategy favoring survival, persistence and host immune evasion. In vitro follow-up experiments using DNA enzymatic digestion, lrg operon mutant strains, and confocal scanning microscopy confirmed the role of C. albicans-mediated enhanced eDNA production in mixed-biofilms on S. aureus tolerance to vancomycin. Combined, these findings provide mechanistic insights into the therapeutic implications of interspecies interactions, underscoring the need for novel strategies to overcome limitations of current therapies.

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BACKGROUND: Airway guidelines recommend an emergency surgical airway as a potential life-saving treatment in a "Can't Intubate, Can't Oxygenate" (CICO) situation. Surgical airways can be achieved either through a cricothyroidotomy or tracheostomy. The current literature has limited data regarding complications of cricothyroidotomy and tracheostomy in an emergency situation. The objective of this systematic review is to analyze complications following cricothyroidotomy and tracheostomy in airway emergencies. METHODS: This synthesis of literature was exempt from ethics approval. Eight databases were searched from inception to October 2018, using a comprehensive search strategy. Studies were included if they were randomized controlled trials or observational studies reporting complications following emergency surgical airway. Complications were classified as minor (evolving to spontaneous remission or not requiring intervention or not persisting chronically), major (requiring intervention or persisting chronically), early (from the start of the procedure up to 7 days) and late (beyond 7 days of the procedure). RESULTS: We retrieved 2659 references from our search criteria. Following the removal of duplicates, title and abstract review, 33 articles were selected for full-text reading. Twenty-one articles were finally included in the systematic review. We found no differences in minor, major or early complications between the two techniques. However, late complications were significantly more frequent in the tracheostomy group [OR (95% CI) 0.21 (0.20-0.22), p < 0.0001]. CONCLUSIONS: Our results demonstrate that cricothyroidotomies performed in emergent situations resulted in fewer late complications than tracheostomies. This finding supports the recommendations from the latest Difficult Airway Society (DAS) guidelines regarding using cricothyroidotomy as the technique of choice for emergency surgical airway. However, emergency cricothyroidotomies should be converted to tracheostomies in a timely fashion as there is insufficient evidence to suggest that emergency cricothyrotomies are long term airways.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) have expanded treatment options for metastatic renal cell carcinoma (mRCC); however, there are limited predictive biomarkers for response to ICIs in this indication, with programmed death-ligand 1 (PD-L1) status demonstrating little predictive utility in mRCC. While predictive of ICI response in other tumor types, the utility of tumor mutation burden (TMB) in mRCC is unclear. Here, we assess TMB, loss of antigen presentation genes and PD-L1 status correlated with outcomes to ICI treatment in mRCC. METHODS: Tumor samples from 34 patients with mRCC treated with ICI therapy at Duke Cancer Institute were retrospectively evaluated using Personal Genome Diagnostics elio tissue complete (RUO version), a tumor genomic profiling assay for somatic variants, TMB, microsatellite status and genomic status of antigen presentation genes. Tumor samples were also analyzed with the Dako 28-8 PD-L1 immunohistochemistry assay. Deidentified clinical information was extracted from the medical record, and tumor response was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1 criteria. RESULTS: Patients were stratified by overall response following ICI therapy and designated as progressive disease (PD; n=18) or disease control groups (DC; n=16). TMB scores ranged from 0.36 to 12.24 mutations/Mb (mean 2.83 mutations/Mb) with no significant difference between the PD and DC groups (3.01 vs 2.63 mutations/Mb, respectively; p=0.7682). Interestingly, 33% of PD patients displayed loss of heterozygosity of major histocompatibility complex class I genes (LOH-MHC) vs 6% of DC patients. Nine of 34 samples were PD-L1-positive (4 in the PD group; 5 in the DC group), suggesting no correlation between PD-L1 expression and response to ICI therapy. Notably, the DC group displayed an enrichment of mutations in DNA repair genes (p=0.04), with 68.8% exhibiting at least one mutated homologous recombination repair (HRR)-related gene compared with only 38.9% of the PD group (p=0.03). CONCLUSIONS: Overall, neither TMB nor PD-L1 correlated with ICI response and TMB was not significantly associated with PD-L1 expression. The higher incidence of LOH-MHC in PD group suggests that loss of antigen presentation may restrict response to ICIs. Separately, enrichment of HRR gene mutations in the DC group suggests potential utility in predicting ICI response and a potential therapeutic target, warranting future studies.

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INTRODUCTION: We assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC. METHODS: In this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS). Associations of c-Myc expression in tumor tissue (prespecified) and genetic alterations in circulating tumor DNA (retrospective) with clinical outcome were evaluated. RESULTS: A total of 178 patients were enrolled (89 in each arm). The median PFS was 3.32 months with alisertib/paclitaxel versus 2.17 months with placebo/paclitaxel (hazard ratio [HR] = 0.77, 95% confidence limit [CI]: 0.557-1.067, p = 0.113 in the intent-to-treat population versus HR = 0.71, 95% CI: 0.509-0.985, p = 0.038 with corrected analysis applied). Among 140 patients with genetic alternations, patients with cell cycle regulator mutations (cyclin-dependent kinase 6 gene [CDK6], retinoblastoma-like 1 gene [RBL1], retinoblastoma-like 2 gene [RBL2], and retinoblastoma 1 gene [RB1]) had significantly improved PFS with alisertib/paclitaxel versus with placebo/paclitaxel (3.68 versus 1.80 months, respectively [HR = 0.395, 95% CI: 0.239-0.654, p = 0.0003]), and overall survival (7.20 versus 4.47 months, respectively [HR = 0.427, 95% CI: 0.259-0.704, p = 0.00085]). A subset of patients with c-Myc expression showed significantly improved PFS with alisertib/paclitaxel. The incidence of grade 3 or higher drug-related adverse events was 67% (58 patients) with alisertib/paclitaxel versus 22% (25 patients) with placebo/paclitaxel. Twelve patients (14%) versus 11 (12%) died on study, including four versus zero treatment-related deaths. CONCLUSIONS: Efficacy signals were seen with alisertib/paclitaxel in relapsed or refractory SCLC. c-Myc expression and mutations in cell cycle regulators may be potential predictive biomarkers of alisertib efficacy; further prospective validations are warranted.

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Microbial species utilize secreted-signaling molecules to coordinate their behavior. Our previous investigations demonstrated a key role for the Candida albicans-secreted quorum-sensing molecule farnesol in modulating Staphylococcus aureus response to antimicrobials in mixed biofilms. In this study, we aimed to provide mechanistic insights into the impact of farnesol on S. aureus within the context of inter-species interactions. To mimic biofilm dynamics, farnesol-sensitized S. aureus cells were generated via sequential farnesol exposure. The sensitized phenotype exhibited dramatic loss of the typical pigment, which we identified as staphyloxanthin, an important virulence factor synthesized by the Crt operon in S. aureus. Additionally, farnesol exposure exerted oxidative-stress as indicated by transcriptional analysis demonstrating alterations in redox-sensors and major virulence regulators. Paradoxically, the activated stress-response conferred S. aureus with enhanced tolerance to H2O2 and phagocytic killing. Since expression of enzymes in the staphyloxanthin biosynthesis pathway was not impacted by farnesol, we generated a theoretical-binding model which indicated that farnesol may block staphyloxanthin biosynthesis via competitive-binding to the CrtM enzyme crucial for staphyloxanthin synthesis, due to high structural similarity to the CrtM substrate. Finally, mixed growth with C. albicans was found to similarly induce S. aureus depigmentation, but not during growth with a farnesol-deficient C. albicans strain. Collectively, the findings demonstrate that a fungal molecule acts as a redox-cycler eliciting a bacterial stress response via activation of the thiol-based redox system under the control of global regulators. Therefore, farnesol-induced transcriptional modulations of key regulatory networks in S. aureus may modulate the pathogenesis of C. albicans-S. aureus co-infections.

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The nanosheet stacking phenomenon in graphene thin films significantly deteriorates their gas-sensing performance. This nanosheet stacking issue should be solved and reduced to enhance the gas detection sensitivity. In this study, we report a novel ammonia (NH3) gas sensor based on holey graphene thin films. The precursors, holey graphene oxide (HGO) nanosheets, were prepared by etching graphene under UV irradiation with Fenton reagent (Fe2+/Fe3+/H2O2). Holey graphene was prepared by the reduction of HGO (rHGO) with pyrrole. Holey graphene thin-film gas sensors were prepared by depositing rHGO suspensions onto the electrodes. The resulting sensing devices show excellent response, sensitivity, and selectivity to NH3. The resistance change is 2.81% when the NH3 level is as low as 1 ppm, whereas the resistance change is 11.32% when the NH3 level is increased to 50 ppm. Furthermore, the rHGO thin-film gas sensor could be quickly restored to their initial states without the stimulation with an IR lamp. In addition, the devices showed excellent repeatability. The resulting rHGO thin-film gas sensor has a great potential for applications in numerous sensing fields because of its low cost, low energy consumption, and outstanding sensing performance.

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WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Success of a cricothyrotomy is dependent on accurate identification of the cricothyroid membrane. The objective of this study was to compare the accuracy of ultrasonography versus external palpation in localizing the cricothyroid membrane. METHODS: In total, 223 subjects with abnormal neck anatomy who were scheduled for neck computed-tomography scan at University Health Network hospitals in Toronto, Canada, were randomized into two groups: external palpation and ultrasound. The localization points of the cricothyroid membrane determined by ultrasonography or external palpation were compared to the reference midpoint (computed-tomography point) of the cricothyroid membrane by a radiologist who was blinded to group allocation. Primary outcome was the accuracy in identification of the cricothyroid membrane, which was measured by digital ruler in millimeters from the computed-tomography point to the ultrasound point or external-palpation point. Success was defined as the proportion of accurate attempts within a 5-mm distance from the computed-tomography point to the ultrasound point or external-palpation point. RESULTS: The percentage of accurate attempts was 10-fold greater in the ultrasound than external-palpation group (81% vs. 8%; 95% CI, 63.6 to 81.3%; P < 0.0001). The mean (SD) distance measured from the external-palpation to computed-tomography point was five-fold greater than the ultrasound to the computed-tomography point (16.6 ± 7.5 vs. 3.4 ± 3.3 mm; 95% CI, 11.67 to 14.70; P < 0.0001). Analysis demonstrated that the risk ratio of inaccurate localization of the cricothyroid membrane was 9.14-fold greater with the external palpation than with the ultrasound (P < 0.0001). There were no adverse events observed. CONCLUSIONS: In subjects with poorly defined neck landmarks, ultrasonography is more accurate than external palpation in localizing the cricothyroid membrane.

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BACKGROUND: Ultrasonography can accurately identify the cricothyroid membrane; however, its impact on the subsequent accuracy of external palpation is not known. In this study, we tested the ability of anesthesia participants to identify the midpoint of the cricothyroid membrane using external palpation with and without ultrasound (US)-guided practice. METHODS: Following institutional ethics approval and informed consent, anesthesia participants consisting of anesthesia residents, fellows, and practicing anesthesia assistants underwent didactic teaching on neck landmarks. The participants were then randomized to practice palpation of neck landmarks with US guidance (US group) or without ultrasonography (non-US [NUS] group). After the practice session, each participant identified the cricothyroid membrane using external palpation on the neck of 10 volunteers and marked the anticipated entry point for device insertion (palpation point [PT]). The midpoint of the cricothyroid membrane of each volunteer had been premarked with invisible ink using ultrasonography (US point) by a separate member of the research team. The primary outcome was the accuracy rate defined as the percentage of the attempts with the distance ≤5 mm measured from the PT to US point for the participant. The primary outcome was compared between NUS and US groups using Wilcoxon rank sum test. A mixed-effect logistic regression or mixed-effect linear model was also conducted for outcomes accounting for the clustering and adjusting for potential confounders. RESULTS: Fifteen anesthesia participants were randomized to US (n = 8) and NUS (n = 7) groups. A total of 80 and 61 attempts were performed by the US and NUS groups, respectively. The median accuracy rate in the US group was higher than the NUS group (65% vs 30%; P = .025), and the median PT-US distance in the US group was shorter than in the NUS group (4.0 vs 8.0 mm; P = .04). The adjusted mean PT-US distance in the US group was shorter compared to the NUS group (adjusted mean [95% CI], 3.6 [2.9-4.6] vs 6.8 [5.2-8.9] mm; P < .001). CONCLUSIONS: Anesthesia participants exposed to practice with US-guided palpation of the cricothyroid membrane location were better able to identify the cricothyroid membrane using only blind palpation than participants without US-guided practice. Practice with US-guided palpation of neck landmarks improves subsequent blind localization of the cricothyroid membrane using palpation alone.

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Airway management is a critical skill in the practice of several medical specialities including anesthesia, emergency medicine, and critical care. Over the years mounting evidence has showed an increasing role of ultrasound (US) in airway management. The objective of this narrative review is to provide an overview of the indications for point-of-care ultrasound (POCUS) of the upper airway. The use of US to guide and assist clinical airway management has potential benefits for both provider and patient. Ultrasound can be utilized to determine airway size and predict the appropriate diameter of single-lumen endotracheal tubes (ETTs), double-lumen ETTs, and tracheostomy tubes. Ultrasonography can differentiate tracheal, esophageal, and endobronchial intubation. Ultrasonography of the neck can accurately localize the cricothyroid membrane for emergency airway access and similarly identify tracheal rings for US-guided tracheostomy. In addition, US can identify vocal cord dysfunction and pathology before induction of anesthesia. A rapidly growing body of evidence showing ultrasonography used in conjunction with hands-on management of the airway may benefit patient care. Increasing awareness and use of POCUS for many indications have resulted in technologic advancements and increased accessibility and portability. Upper airway POCUS has the potential to become the first-line non-invasive adjunct assessment tool in airway management.

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