Channelled versus nonchannelled Macintosh videolaryngoscope blades in patients with a cervical collar: a randomized controlled noninferiority trial.

PURPOSE: Channelled blades have the advantage of avoiding stylet use and potential airway injury during videolaryngoscopic intubation. Nevertheless, the effectiveness of channelled Macintosh-type blades has not yet been fully established. We sought to assess the utility of channelled Macintosh-type blades for videolaryngoscopic intubation under cervical spine immobilization. METHODS: We conducted a randomized controlled noninferiority trial in neurosurgical patients with a difficult airway simulated by a cervical collar. Videolaryngoscopic intubation with a reinforced tracheal tube was performed using a channelled Macintosh-type blade without a stylet (channelled group, n = 130) or a nonchannelled Macintosh-type blade with a stylet (nonchannelled group, n = 131). The primary outcome was intubation success rate. Secondary outcomes included time to intubation and incidence or severity of intubation-related complications (subglottic, lingual, and dental injuries; bleeding; sore throat; and hoarseness). RESULTS: The initial intubation success rate was 98% and 99% in the channelled and nonchannelled groups, respectively, showing the noninferiority of the channelled group (difference in proportions -0.8%; 95% confidence interval [CI], -4.8% to 2.9%; predefined noninferiority margin, -5%; P = 0.62). Fewer participants in the channelled group had subglottic injuries than in the nonchannelled group (32% [32/100] vs 57% [54/95]; difference in proportions, -25%; 95% CI, -39% to -11%; P < 0.001). There were no significant differences between the two groups in the overall intubation success rate, time to intubation, and incidence or severity of other intubation-related complications. CONCLUSIONS: For videolaryngoscopic intubation in patients with a cervical collar, channelled Macintosh-type blades are an alternative to nonchannelled Macintosh-type blades, with a noninferior initial intubation success rate and a lower incidence of subglottic injury. STUDY REGISTRATION: CRIS.nih.go.kr ( KCT0005186 ); first submitted 29 June 2020.

RéSUMé: OBJECTIF: Les lames avec canal ont l'avantage de ne pas nécessiter l'utilisation d'un stylet et d'ainsi éviter les lésions potentielles des voies aériennes lors de l'intubation vidéolaryngoscopique. Néanmoins, l'efficacité des lames avec canal de type Macintosh n'a pas encore été pleinement établie. Nous avons cherché à évaluer l'utilité des lames avec canal de type Macintosh pour l'intubation vidéolaryngoscopique lorsque le rachis cervical était immobilisé. MéTHODE: Nous avons mené une étude randomisée contrôlée de non-infériorité chez des patient·es de neurochirurgie présentant des voies aériennes difficiles simulées par le port d'un collier cervical. L'intubation vidéolaryngoscopique avec une sonde trachéale renforcée a été réalisée à l'aide d'une lame Macintosh avec canal sans stylet (groupe avec canal, n = 130) ou d'une lame Macintosh sans canal avec stylet (groupe sans canal, n = 131). Le critère d'évaluation principal était le taux de réussite de l'intubation. Les critères d'évaluation secondaires comprenaient le temps d'intubation et l'incidence ou la gravité des complications liées à l'intubation (lésions sous-glottiques, linguales et dentaires, saignements, maux de gorge et enrouement). RéSULTATS: Le taux de réussite initial de l'intubation était de 98 % et 99 % dans les groupes avec et sans canal, respectivement, montrant la non-infériorité du groupe lame avec canal (différence de proportions −0,8 %; intervalle de confiance [IC] à 95 %, −4,8 % à 2,9 %; marge de non-infériorité prédéfinie, −5 %; P = 0,62). Les lésions sous-glottiques ont été moins nombreuses dans le groupe avec canal que dans le groupe sans canal (32 % [32/100] vs 57 % [54/95]; différence de proportions, −25 %; IC 95 %, −39 % à −11 %; P < 0,001). Il n'y avait pas de différences significatives entre les deux groupes en matière de taux global de réussite de l'intubation, de temps d'intubation et d'incidence ou de gravité des autres complications liées à l'intubation. CONCLUSION: Pour l'intubation vidéolaryngoscopique des patient·es portant un collier cervical, les lames avec canal de type Macintosh constituent une alternative aux lames sans canal de type Macintosh, avec un taux de réussite d'intubation initial non inférieur et une incidence plus faible de lésions sous-glottiques. ENREGISTREMENT DE L'éTUDE: CRIS.nih.go.kr ( KCT0005186 ); première soumission le 29 juin 2020.

Effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin measurements in liver transplantation recipients.

This study evaluated the effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin (SpHb) measurements in liver transplantation recipients. Overall, 1465 SpHb and laboratory hemoglobin (Hb) measurement pairs (n = 296 patients) were analyzed. Patients were grouped into normal (< 1.2 mg/dL), mild-to-moderate (1.2-3.0 mg/dL), and severe (> 3.0 mg/dL) hyperbilirubinemia groups based on the preoperative serum total bilirubin levels. Bland-Altman analysis showed a bias of 0.20 (95% limit of agreement, LoA: - 2.59 to 3.00) g/dL, 0.98 (95% LoA: - 1.38 to 3.35) g/dL, and 1.23 (95% LoA: - 1.16 to 3.63) g/dL for the normal, mild-to-moderate, and severe groups, respectively. The four-quadrant plot showed reliable trending ability in all groups (concordance rate > 92%). The rates of possible missed transfusion (SpHb > 7.0 g/dL for Hb < 7.0 g/dL) were higher in the hyperbilirubinemia groups (2%, 7%, and 12% for the normal, mild-to-moderate, and severe group, respectively. all P < 0.001). The possible over-transfusion rate was less than 1% in all groups. In conclusion, the use of SpHb in liver transplantation recipients with preoperative hyperbilirubinemia requires caution due to the positive bias and high risk of missed transfusion. However, the reliable trending ability indicated its potential use in clinical settings.

The impact of preoperative coronavirus disease 19 infection on early postoperative mortality during the vaccination era: a nationwide retrospective cohort study.

BACKGROUND: We aimed to investigate the optimal surgical timing in patients with preoperative coronavirus disease 2019 (COVID-19) infection to minimize postoperative morbidity and mortality during the COVID-19 vaccination era. METHODS: The Korean nationwide data on patients who underwent standard surgery under general anesthesia in 2021 were analyzed. Patients were categorized based on the time from COVID-19 diagnosis to surgery: 0-4, 5-8, > 8 weeks, and those without preoperative COVID-19 infection. Multivariable logistic regression analysis, considering preoperative COVID-19 vaccination status (fully vaccinated vs. unvaccinated or partially vaccinated), was performed to associate the preoperative COVID-19 infection timing with 30- and 90-day postoperative mortality and 30-day respiratory complications. RESULTS: Among the 750,175 included patients, 28.2% were preoperatively fully vaccinated. Compared with patients without prior COVID-19 infection, those who had surgery 0-4 weeks (adjusted odds ratio [OR]: 4.28, 95% CI [1.81, 10.13], P = 0.001) and 5-8 weeks (adjusted OR: 3.38, 95% CI [1.54, 7.44], P = 0.002) after COVID-19 infection had a significantly increased risk of 30-day mortality. Preoperative full vaccination was significantly associated with a decrease in 90-day mortality (adjusted OR: 0.93, 95% CI [0.89, 0.98], P = 0.007) and 30-day respiratory complications (adjusted OR: 0.85, 95% CI [0.82, 0.87], P < 0.001), but not with 30-day mortality (P = 0.916). CONCLUSIONS: COVID-19 infection eight weeks preoperatively was associated with an increased 30-day postoperative mortality. Preoperative full vaccination was not associated with 30-day mortality but was related to lower risk of 90-day mortality and 30-day respiratory complications.

Usefulness of C-curved stylet for intubation with the C-MAC® Miller videolaryngoscope in neonates and infants: a prospective randomized controlled trial.

BACKGROUND: Optimizing endotracheal tube (ETT) shape is important for successful videolaryngoscope-aided intubation. This prospective randomized controlled study aimed to compare the tube-handling time between a C-curved and hockey stick-shaped stylet in infants and neonates using the C-MAC® videolaryngoscope Miller blade. METHODS: A total of 110 infants (age < 1 year) were randomly assigned to either the hockey stick-curved stylet group (group H, n = 53) or the C-curved stylet group (group C, n = 57). The primary outcome was tube handling time after glottis visualization and the secondary outcomes were the total intubation time, incidence of successful intubation, initial tube tip location at the laryngeal inlet, and numerical rating scale for ease of intubation. RESULTS: Tube insertion time and total intubation duration (both in seconds) were significantly shorter in group C than in group H (13.3 ± 8.9 vs. 25.1 ± 27.0, P = 0.002; 19.9 ± 9.4 vs. 32.8 ± 27.1, P = 0.001, respectively). Group C displayed a higher rate of intubation success within 30 s than group H (87.7% vs. 69.8%, P = 0.029). The initial tube tip was located at the center in 34 children in group C (59.6%) and 12 children in group H (26.1%, P < 0.001). Laryngoscope operators rated intubation as easier when provided with a C-curved stylet. CONCLUSIONS: In neonates and infants, modification of the ETT shape into a C-curve may reduce tube handling time compared to the conventional hockey stick-shaped tube during intubation using a C-MAC® video laryngoscope Miller blade.

Development and evaluation of haltere-mimicking gyroscope for three-axis angular velocity sensing using a haltere-mimicking structure pair.

This paper presents a three-axis biomimetic gyroscope, mimicking the haltere of Diptera. Diptera use a club-shaped mechanosensory organ called the haltere to get the three-axis angular velocity information, namely roll, pitch and yaw axes, for flight control. One pair of halteres is physically connected to the wings of Diptera that vibrate in antiphase to the flapping wings in ambient air. They sense the Coriolis force and relay angular velocity information to the Diptera. As an alternative to the conventional micro-electro-mechanical system gyroscopes which are widely used in robotics, many research groups have attempted to mimic the haltere. However, no previous study succeeded in measuring all three-axis components of angular velocity, due to various shortcomings. In this paper, we developed the first three-axis haltere-mimicking gyroscope. Two perpendicularly positioned haltere-mimicking structures that can vibrate at a 180° amplitude were mechanically integrated into a robot actuator. Two accelerometers, placed at the tip of each structure, were employed to measure the Coriolis force. The performance of the novel biomimetic gyroscope was measured in all rotational directions, using a motion capture system as the ground truth. One-axis input experiments were performed 240 times at different input magnitudes and directions, and the measured orientation error was less than ±2.0% in all experiments. In 80 three-axis input experiments, the orientation error was less than ±3.5%.

A Four-Channel Low-Noise Readout IC for Air Flow Measurement Using Hot Wire Anemometer in 0.18 µm CMOS Technology.

Air flow measurements provide significant information required for understanding the characteristics of insect movement. This study proposes a four-channel low-noise readout integrated circuit (IC) in order to measure air flow (air velocity), which can be beneficial to insect biomimetic robot systems that have been studied recently. Instrumentation amplifiers (IAs) with low-noise characteristics in readout ICs are essential because the air flow of an insect's movement, which is electrically converted using a microelectromechanical systems (MEMS) sensor, generally produces a small signal. The fundamental architecture employed in the readout IC is a three op amp IA, and it accomplishes low-noise characteristics by chopping. Moreover, the readout IC has a four-channel input structure and implements an automatic offset calibration loop (AOCL) for input offset correction. The AOCL based on the binary search logic adjusts the output offset by controlling the input voltage bias generated by the R-2R digital-to-analog converter (DAC). The electrically converted air flow signal is amplified using a three op amp IA, which is passed through a low-pass filter (LPF) for ripple rejection that is generated by chopping, and converted to a digital code by a 12-bit successive approximation register (SAR) analog-to-digital converter (ADC). Furthermore, the readout IC contains a low-dropout (LDO) regulator that enables the supply voltage to drive digital circuits, and a serial peripheral interface (SPI) for digital communication. The readout IC is designed with a 0.18 µm CMOS process and the current consumption is 1.886 mA at 3.3 V supply voltage. The IC has an active area of 6.78 mm2 and input-referred noise (IRN) characteristics of 95.4 nV/√Hz at 1 Hz.

In Situ Subcellular Detachment of Cells Using a Cell-Friendly Photoresist and Spatially Modulated Light.

Dynamic adhesion and detachment of subcellular regions occur during cell migration, thus a technique allowing precise control of subcellular detachment of cells will be useful for cell migration study. Previous methods for cell detachment were developed either for harvesting cells or cell sheets attached on surfaces with low resolution patterning capability, or for detaching subcellular regions located on predefined electrodes. In this paper, a method that allows in situ subcellular detachment of cells with ≈1.5 µm critical feature size while observing cells under a fluorescence microscope is introduced using a cell-friendly photoresist and spatially modulated light. Using this method, a single cell, regions in cell sheets, and a single focal adhesion complex within a cell are successfully detached. Furthermore, different subcellular regions of migrating cells are detached and changes in cell polarity and migration direction are quantitatively analyzed. This method will be useful for many applications in cell detachment, in particular when subcellular resolution is required.

Characterization of the Piezoresistive Effects of Silicon Nanowires.

Silicon nanowires (SiNWs) have received attention in recent years due to their anomalous piezoresistive (PZR) effects. Although the PZR effects of SiNWs have been extensively researched, they are still not fully understood. Herein, we develop a new model of the PZR effects of SiNWs to characterize the PZR effects. First, the resistance of SiNW is modeled based on the surface charge density. The characteristics of SiNW, such as surface charge and effective conducting area, can be estimated by using this resistance model. Then, PZR effects are modeled based on stress concentration and piezopinch effects. Stress concentration as a function of the physical geometry of SiNWs can amplify PZR effects by an order of magnitude. The piezopinch effects can also result in increased PZR effects that are at least two times greater than that of bulk silicon. Experimental results show that the proposed model can predict the PZR effects of SiNWs accurately.

Bone-patellar tendon-bone autograft could be recommended as a superior graft to hamstring autograft for ACL reconstruction in patients with generalized joint laxity: 2- and 5-year follow-up study.

PURPOSE: The present study aimed to compare 2- and 5-year outcomes of ACL reconstruction between patients with and without generalized joint laxity and to perform comparative evaluation between two types of grafts used for ACL reconstruction in patients with generalized joint laxity. METHODS: Two hundred and thirty-seven patients who underwent ACL reconstruction from 2001 to 2008 were included. Patients were classified into two groups according to the presence or the absence of generalized joint laxity, and further subdivided into two subgroups based on the type of graft used: bone-patellar tendon-bone (BPTB) or hamstring. Generalized joint laxity was assessed with the Beighton and Horan criteria using a point scoring system. Stability reflected by the Lachman test, pivot-shift test, and anterior translation measured with KT-2000, and functional outcomes reflected by Lysholm knee score, and International Knee Documentation Committee (IKDC) subjective score were investigated. IKDC objective grade and radiographic grade were also assessed. Clinical assessments were conducted preoperatively and at 2 and 5 years after operation. RESULTS: Two-year follow-up results showed that patients with generalized joint laxity receiving hamstring grafts had poorer outcomes than those without generalized joint laxity. Five-year follow-up results showed that patients with generalized joint laxity experienced poorer outcomes than patients without generalized joint laxity, irrespective of the type of graft. Comparison of grafts used showed that, in patients with generalized joint laxity, BPTB graft provided significantly better stability and functional outcomes than hamstring graft at both 2- and 5-year follow-ups. Comparisons between serial outcomes measured at 2 and 5 years demonstrated that stability and functional outcomes deteriorated over time in patients with generalized joint laxity. CONCLUSIONS: Less satisfactory stability and functional outcomes were noted in patients with generalized joint laxity, compared to patients without generalized joint laxity. Comparisons of stability and functional outcomes after ACL reconstruction in patients with generalized joint laxity between two different grafts demonstrated that BPTB graft achieves better results than hamstring graft. LEVEL OF EVIDENCE: III, a retrospective cohort study.

Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which metal chelation modulates morphogenetic circuitry and echinocandin resistance, and illuminate a novel facet to metal homeostasis at the host-pathogen interface, with broad therapeutic potential.

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.

Dual action antifungal small molecule modulates multidrug efflux and TOR signaling.

There is an urgent need for new strategies to treat invasive fungal infections, which are a leading cause of human mortality. Here, we establish two activities of the natural product beauvericin, which potentiates the activity of the most widely deployed class of antifungal against the leading human fungal pathogens, blocks the emergence of drug resistance, and renders antifungal-resistant pathogens responsive to treatment in mammalian infection models. Harnessing genome sequencing of beauvericin-resistant mutants, affinity purification of a biotinylated beauvericin analog, and biochemical and genetic assays reveals that beauvericin blocks multidrug efflux and inhibits the global regulator TORC1 kinase, thereby activating the protein kinase CK2 and inhibiting the molecular chaperone Hsp90. Substitutions in the multidrug transporter Pdr5 that enable beauvericin efflux impair antifungal efflux, thereby impeding resistance to the drug combination. Thus, dual targeting of multidrug efflux and TOR signaling provides a powerful, broadly effective therapeutic strategy for treating fungal infectious disease that evades resistance.

Systematic functional profiling of transcription factor networks in Cryptococcus neoformans.

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.

Network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. Due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of C. neoformans is imperative. The analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phenotypes but with limited efficiency. Here, we present a genome-scale co-functional network for C. neoformans, CryptoNet, which covers ~81% of the coding genome and provides an efficient intermediary between functional genomics data and reverse-genetics resources for the genetic dissection of C. neoformans phenotypes. CryptoNet is the first genome-scale co-functional network for any fungal pathogen. CryptoNet effectively identified novel genes for pathogenicity and drug resistance using guilt-by-association and context-associated hub algorithms. CryptoNet is also the first genome-scale co-functional network for fungi in the basidiomycota phylum, as Saccharomyces cerevisiae belongs to the ascomycota phylum. CryptoNet may therefore provide insights into pathway evolution between two distinct phyla of the fungal kingdom. The CryptoNet web server (www.inetbio.org/cryptonet) is a public resource that provides an interactive environment of network-assisted predictive genetics for C. neoformans.