Isolation of wild yeasts from Olympic National Park and Moniliella megachiliensis ONP131 physiological characterization for beer fermentation.

Thousands of yeasts have the potential for industrial application, though many were initially considered contaminants in the beer industry. However, these organisms are currently considered important components in beers because they contribute new flavors. Non-Saccharomyces wild yeasts can be important tools in the development of new products, and the objective of this work was to obtain and characterize novel yeast isolates for their ability to produce beer. Wild yeasts were isolated from environmental samples from Olympic National Park and analyzed for their ability to ferment malt extract medium and beer wort. Six different strains were isolated, of which Moniliella megachiliensis ONP131 displayed the highest levels of attenuation during fermentations. We found that M. megachiliensis could be propagated in common yeast media, tolerated incubation temperatures of 37 °C and a pH of 2.5, and was able to grow in media containing maltose as the sole carbon source. Yeast cultivation was considerably impacted (p < 0.05) by lactic acid, ethanol, and high concentrations of maltose, but ONP131 was tolerant to high salinity and hop acid concentrations. This is one of the first physiological characterizations of M. megachiliensis, which has potential for the production of beer and other fermented beverages.

Robotic Complete Mesocolic Excision (CME) is a safe and feasible option for right colonic cancers: short and midterm results from a single-centre experience.

BACKGROUND: Complete mesocolic excision (CME) for right colon cancers has traditionally been an open procedure. Surgical adoption of minimal access CME remains limited due to the technical challenges, training gaps and lack of level-1 data for proven benefits. Currently there is limited published data regarding the clinical results with the use of robotic CME surgery. Aim To report our experience, results and techniques, highlighting a clinical and oncological results and midterm oncological outcomes for robotic CME. AIM: To report our experience, results and techniques, highlighting a clinical and oncological results and midterm oncological outcomes for robotic CME. METHODS: All patients undergoing standardised robotic CME technique with SMV first approach between January 2015 and September 2019 were included in this retrospective review of a prospectively collected database. Patient demographics, operative data and clinical and oncological outcomes were recorded. RESULTS: Seventy-seven robotic CME resections for right colonic cancers were performed over a 4-year period. Median operative time was 180 (128-454) min and perioperative blood loss was 10 (10-50) ml. There were 25 patients who had previous abdominal surgery. Median postoperative hospital stay was 5 (3-18) days. There was no conversion to open surgery in this series. Median lymph node count was 30 (10-60). Three (4%) patients had R1 resection. There was one (1%) local recurrence in stage III disease and 4(5%) distal recurrence in stage II and stage III. There was no 30- or 90-day mortality. Three-year disease-free survival was 100%, 91.7% and 92% for stages I, II and III, respectively. Overall survival was 94%. CONCLUSIONS: Robotic CME is feasible, effective and safe. Good oncological results and improved survival are seen in this cohort of patients with a standardised approach to robotic CME.

Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates.

OBJECTIVE: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation. DESIGN: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS). SETTING: Eighteen academic NICUs in NEAR4NEOS. PATIENTS: Neonates requiring two or more attempts at intubation between October 2014 and December 2021. MAIN OUTCOME MEASURES: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice. RESULTS: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs. CONCLUSIONS: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.

A clinical decision aid for the selection of antithrombotic therapy for the prevention of stroke due to atrial fibrillation.

AIMS: The availability of new antithrombotic agents, each with a unique efficacy and bleeding profile, has introduced a considerable amount of clinical uncertainty with physicians. We have developed a clinical decision aid in order to assist clinicians in determining an optimal antithrombotic regime for the prevention of stroke in patients who are newly diagnosed with non-valvular atrial fibrillation. METHODS AND RESULTS: The CHA(2)DS(2)-VASc and HAS-BLED scoring systems were used to assess patients' baseline risks of stroke and major bleeding, respectively. The relative risks of stroke and major bleeding for each antithrombotic agent were then used to identify the agent associated with the lowest net risk. Individual patient factors such as the treatment threshold, bleeding ratio, and cost threshold modified the recommendations in order to generate a final recommendation. By considering both patient factors and clinical research concurrently, this clinical decision aid is able to provide specific advice to clinicians regarding an optimal stroke prevention strategy. The resulting treatment recommendation tables are consistent with the recommendations of the European Society of Cardiology and Canadian Cardiovascular Society Guidelines, which can be incorporated into either a paper-based or electronic format to allow clinicians to have decision support at the point of care. CONCLUSION: The use of a clinical decision aid that considers both patient factors and evidence-based medicine will serve to bridge the knowledge gap and provide practical guidance to clinicians in the prevention of stroke due to atrial fibrillation.

Robotic CME in obese patients: advantage of robotic ultrasound scan for vascular dissection.

Complete mesocolic excision (CME) in right-sided colon cancers appears to confer oncological benefits compared to conventional colectomy. Identification of the superior mesenteric vein (SMV) remains challenging. We describe the novel use of intra-operative robotic ultrasound scan (rUSS) in obese patients (BMI ≥ 29). All consecutive patients having robotic CME for colon cancer between 2014 and 2017 were included in this retrospective cohort study. Data were recorded on an ethics approved prospective database and included patient demographics, clinical and oncological outcomes. Patients were divided into group 1 (BMI ≤ 28) and group 2 (BMI ≥ 29). SMV first approach was employed in all cases and SMV detection was aided using rUSS in group 2. Primary outcome was postoperative morbidity. Secondary outcomes included conversion rate, operative time and length of stay (LOS). 41 (group 1, median 66 years) were compared to 32 patients (group 2, median 63 years). There were no conversions to laparoscopy or laparotomy. Median operative times for group 2 were 30 min longer (186 vs. 216 min, p = 0.05). Overall morbidity was similar (20% vs. 19% in group 1 and 2, p = 0.26). There was no significant difference between the two groups with regard to LOS (median 7 vs. 6 days, p = 0.48), readmissions (2 vs. 5, p = 0.13), R0 resection rate (98% vs. 94%, p = 0.43) and lymph node harvest (median 31 vs. 30, p = 0.28).CME can be technically more challenging than conventional colectomy in obese patients and is associated with longer operative times. The use of rUSS in obese patients can help to identify SMV and allow safer dissection.

Lung volume changes during apnoeas in preterm infants.

OBJECTIVE: Mechanisms of non-invasive high-frequency oscillatory ventilation (nHFOV) in preterm infants are unclear. We aimed to compare lung volume changes during apnoeas in preterm infants on nHFOV and nasal continuous positive airway pressure (nCPAP). METHODS: Analysis of electrical impedance tomography (EIT) data from a randomised crossover trial comparing nHFOV with nCPAP in preterm infants at 26-34 weeks postmenstrual age. EIT data were screened by two reviewers to identify apnoeas ≥10 s. End-expiratory lung impedance (EELI) and tidal volumes (VT) were calculated before and after apnoeas. Oxygen saturation (SpO2) and heart rate (HR) were extracted for 60 s after apnoeas. RESULTS: In 30 preterm infants, 213 apnoeas were identified. During apnoeas, oscillatory volumes were detectable during nHFOV. EELI decreased significantly during apnoeas (∆EELI nCPAP: -8.0 (-11.9 to -4.1) AU/kg, p<0.001; ∆EELI nHFOV: -3.4 (-6.5 to -0.3), p=0.03) but recovered over the first five breaths after apnoeas. Compared with before apnoeas, VT was increased for the first breath after apnoeas during nCPAP (∆VT: 7.5 (3.1 to 11.2) AU/kg, p=0.001). Falls in SpO2 and HR after apnoeas were greater during nCPAP than nHFOV (mean difference (95% CI): SpO2: 3.6% (2.7 to 4.6), p<0.001; HR: 15.9 bpm (13.4 to 18.5), p<0.001). CONCLUSION: Apnoeas were characterised by a significant decrease in EELI which was regained over the first breaths after apnoeas, partly mediated by a larger VT. Apnoeas were followed by a considerable drop in SpO2 and HR, particularly during nCPAP, leading to longer episodes of hypoxemia during nCPAP. Transmitted oscillations during nHFOV may explain these benefits. TRIAL REGISTRATION NUMBER: ACTRN12616001516471.

Neonatal high-frequency oscillatory ventilation: where are we now?

High-frequency oscillatory ventilation (HFOV) is an established mode of respiratory support in the neonatal intensive care unit. Large clinical trial data is based on first intention use in preterm infants with acute respiratory distress syndrome. Clinical practice has evolved from this narrow population. HFOV is most often reserved for term and preterm infants with severe, and often complex, respiratory failure not responding to conventional modalities of respiratory support. Thus, optimal, and safe, application of HFOV requires the clinician to adapt mean airway pressure, frequency, inspiratory:expiratory ratio and tidal volume to individual patient needs based on pathophysiology, lung volume state and infant size. This narrative review summarises the status of HFOV in neonatal intensive care units today, the lessons that can be learnt from the past, how to apply HFOV in different neonatal populations and conditions and highlights potential new advances. Specifically, we provide guidance on how to apply an open lung approach to mean airway pressure, selecting the correct frequency and use of volume-targeted HFOV.

Lung volume distribution in preterm infants on non-invasive high-frequency ventilation.

INTRODUCTION: Non-invasive high-frequency oscillatory ventilation (nHFOV) is an extension of nasal continuous positive airway pressure (nCPAP) support in neonates. We aimed to compare global and regional distribution of lung volumes during nHFOV versus nCPAP. METHODS: In 30 preterm infants enrolled in a randomised crossover trial comparing nHFOV with nCPAP, electrical impedance tomography data were recorded in prone position. For each mode of respiratory support, four episodes of artefact-free tidal ventilation, each comprising 30 consecutive breaths, were extracted. Tidal volumes (VT) in 36 horizontal slices, indicators of ventilation homogeneity and end-expiratory lung impedance (EELI) for the whole lung and for four horizontal regions of interest (non-gravity-dependent to gravity-dependent; EELINGD, EELImidNGD, EELImidGD, EELIGD) were compared between nHFOV and nCPAP. Aeration homogeneity ratio (AHR) was determined by dividing aeration in non-gravity-dependent parts of the lung through gravity-dependent regions. MAIN RESULTS: Overall, 228 recordings were analysed. Relative VT was greater in all but the six most gravity-dependent lung slices during nCPAP (all p<0.05). Indicators of ventilation homogeneity were similar between nHFOV and nCPAP (all p>0.05). Aeration was increased during nHFOV (mean difference (95% CI)=0.4 (0.2 to 0.6) arbitrary units per kilogram (AU/kg), p=0.013), mainly due to an increase in non-gravity-dependent regions of the lung (∆EELINGD=6.9 (0.0 to 13.8) AU/kg, p=0.028; ∆EELImidNGD=6.8 (1.2 to 12.4) AU/kg, p=0.009). Aeration was more homogeneous during nHFOV compared with nCPAP (mean difference (95% CI) in AHR=0.01 (0.00 to 0.02), p=0.0014). CONCLUSION: Although regional ventilation was similar between nHFOV and nCPAP, end-expiratory lung volume was higher and aeration homogeneity was slightly improved during nHFOV. The aeration difference was greatest in non-gravity dependent regions, possibly due to the oscillatory pressure waveform. The clinical importance of these findings is still unclear.

Aeration strategy at birth influences the physiological response to surfactant in preterm lambs.

BACKGROUND: The influence of pressure strategies to promote lung aeration at birth on the subsequent physiological response to exogenous surfactant therapy has not been investigated. OBJECTIVES: To compare the effect of sustained inflation (SI) and a dynamic positive end-expiratory pressure (PEEP) manoeuvre at birth on the subsequent physiological response to exogenous surfactant therapy in preterm lambs. METHODS: Steroid-exposed preterm lambs (124-127 days' gestation; n=71) were randomly assigned from birth to either (1) positive-pressure ventilation (PPV) with no recruitment manoeuvre; (2) SI until stable aeration; or (3) 3 min dynamic stepwise PEEP strategy (maximum 14-20 cmH2O; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol. Surfactant (200 mg/kg poractant alfa) was administered at 10 min. Dynamic compliance, gas exchange and regional ventilation and aeration characteristics (electrical impedance tomography) were measured throughout and compared between groups, and with a historical group (n=38) managed using the same strategies without surfactant. RESULTS: Compliance increased after surfactant only in the DynPEEP group (p<0.0001, repeated measures analysis of variance), being 0.17 (0.10, 0.23) mL/kg/cmH2O higher at 60 min than the SI group. An SI resulted in the least uniform aeration, and unlike the no-recruitment and DynPEEP groups, the distribution of aeration and tidal ventilation did not improve with surfactant. All groups had similar improvements in oxygenation post-surfactant compared with the corresponding groups not treated with surfactant. CONCLUSIONS: A DynPEEP strategy at birth may improve the response to early surfactant therapy, whereas rapid lung inflation with SI creates non-uniform aeration that appears to inhibit surfactant efficacy.

Volume guaranteed? Accuracy of a volume-targeted ventilation mode in infants.

OBJECTIVES: Volume-targeted ventilation (VTV) is widely used and may reduce lung injury, but this assumes the clinically set tidal volume (VTset) is accurately delivered. This prospective observational study aimed to determine the relationship between VTset, expiratory VT (VTe) and endotracheal tube leak in a modern neonatal -volume-targeted ventilator (VTV) and the resultant partial arterial pressure of carbon dioxide (PaCO2) relationship with and without VTV. DESIGN: Continuous inflations were recorded for 24 hours in 100 infants, mean (SD) 34 (4) weeks gestation and 2483 (985) g birth weight, receiving synchronised mechanical ventilation (SLE5000, SLE, UK) with or without VTV and either the manufacturer's V4 (n=50) or newer V5 (n=50) VTV algorithm. The VTset, VTe and leak were determined for each inflation (maximum 90 000/infant). If PaCO2 was sampled (maximum of 2 per infant), this was compared with the average VTe data from the preceding 15 min. RESULTS: A total of 7 497 137 inflations were analysed. With VTV enabled (77 infants), the VTset-VTe bias (95% CI) was 0.03 (-0.12 to 0.19) mL/kg, with a median of 80% of VTe being ±1.0 mL/kg of VTset. Endotracheal tube leak up to 30% influenced VTset-VTe bias with the V4 (r2=-0.64, p<0.0001; linear regression) but not V5 algorithm (r2=0.04, p=0.21). There was an inverse linear relationship between VTe and PaCO2 without VTV (r2=0.26, p=0.004), but not with VTV (r2=0.04, p=0.10), and less PaCO2 within 40-60 mm Hg, 53% versus 72%, relative risk (95% CI) 1.7 (1.0 to 2.9). CONCLUSION: VTV was accurate and reliable even with moderate leak and PaCO2 more stable. VTV algorithm differences may exist in other devices.

End tidal carbon dioxide is as reliable as transcutaneous monitoring in ventilated postsurgical neonates.

OBJECTIVES: To compare the agreement, precision and repeatability of end tidal carbon dioxide (EtCO2 ) and transcutaneous carbon dioxide (TcCO2 ) with partial pressure of arterial CO(2) ( PaCO2) in postoperative neonates. PATIENTS: Fifty mechanically ventilated neonates without lung disease, and with no contraindications for either TcCO2 or EtCO2 monitoring. INTERVENTIONS: Paired TcCO2 and EtCO2 values were recorded with three consecutive measurements within the first 48 h of surgery. MAIN OUTCOME MEASURES: EtCO2, TcCO2 and PaCO2 triplets were compared using Bland-Altman plots. RESULTS: One hundred thirty-two triplet measures of CO(2) were recorded with mean PaCO2 43.5 (7.3) mm Hg, EtCO2 38.8 (6.4) mm Hg and 43.8 (8.8) mm Hg (p<0.0001 for EtCO2 against PaCO2; paired t test). The PaCO2 - EtCO2 bias±2SD was 4.1±9.0 mm Hg and -0.8±13.0 mm Hg for PaCO2 - TcCO2. 56.1% of EtCO2, and 60.6% of TcCO2 values were within ±5 mm Hg of paired PaCO2. CONCLUSIONS: In postoperative neonates, EtCO2 and TcCO2 demonstrated a clinically acceptable agreement with PaCO2.

Speed, road injury, and public health.

We review milestones in the history of increases in speed limits and travel speeds ("speed creep") and risks for road deaths and injury. Reduced speed limits, speed-camera networks, and speed calming substantially reduce these tolls in absolute numbers-a trend that is apparent in the United Kingdom, Australia, France, and other countries, but not in the United States, which has raised speed limits and does not have speed-camera networks. Newtonian relationships between the fourth power of small increases or reductions in speed and large increases or reductions in deaths state the case for speed control. Speed adaptation and the interaction between speed and other determinants of injury risks, including congestion and countermeasures, enter into these relationships. Speed-camera networks and speed calming lead to large, sustainable, and highly cost-effective drops in road deaths and injuries and should target entire populations, not merely high-risk subgroups or situations. Yet, there are major barriers to preventive strategies based on the discovery that speed kills. Modal shifts from speed on roads to speed on rail, lower maximum vehicle speeds, and speed-camera networks are required for progress toward Vision Zero-the goal of no road deaths-through Killing Speed. The human cost of the delay in killing speed in the United States may be as high as 20,000 lives lost per year.