High VT Research Articles

Cell fusing agent virus rarely transmits vertically in artificially infected laboratory-colonized Aedes aegypti mosquitoes

BackgroundVertical transmission (VT) of arboviruses (arthropod-borne viruses) can serve as an essential link in the transmission cycle during adverse environmental conditions. The extent of VT among mosquito-borne arboviruses can vary significantly among different virus families and even among different viruses within the same genus. For example, orthobunyaviruses exhibit a higher VT rate than orthoflaviviruses and alphaviruses. Mosquitoes are also the natural hosts of a large number of insect-specific viruses (ISV) that belong to several virus families, including Bunyaviridae, Flaviviridae, and Togaviridae. Cell fusing agent virus (CFAV), an insect-specific orthoflavivirus, displays higher VT rates than other dual-host orthoflaviviruses, such as Zika and dengue viruses. High VT rates require establishment of stabilized infections in the germinal tissues of female vectors. To delve deeper into understanding the mechanisms governing these differences in VT rates and the establishment of stabilized infections, the ovary infection patterns and VT of Zika virus (ZIKV) and CFAV were compared.MethodsLaboratory colonized Aedes aegypti females were infected with either ZIKV or CFAV by intrathoracic injection. Ovary infection patterns were monitored by in situ hybridization using virus-specific probes, and VT was determined by detecting the presence of the virus among the progeny, using a reverse-transcription quantitative polymerase chain reaction (PCR) assay.ResultsBoth ZIKV and CFAV infect mosquito ovaries after intrathoracic injection. Infections then become widespread following a non-infectious blood meal. VT rates of ZIKV are similar to previously reported results (3.33%). CFAV, on the contrary transmits vertically very rarely. VT was not observed in the first gonotrophic cycle following intrathoracic injection, and only rarely in the second gonotrophic cycle. VT of CFAV is mosquito population independent, since similar results were obtained with Aedes aegypti collected from two different geographic locations.ConclusionsAlthough CFAV infects mosquito ovaries, the occurrence of VT remains infrequent in artificially infected Ae. aegypti, despite the observation of high VT rates in field-collected mosquitoes. These results suggest that infections of insect-specific viruses are stabilized in mosquitoes by some as yet unidentified mechanisms.Graphical

Effects of tidal volume on physiology and clinical outcomes in patients with one‑lung ventilation undergoing surgery: A meta‑analysis of randomized controlled trials.

There is no detailed study on how tidal volume (VT) affects patients during one-lung ventilation (OLV). The present study conducted a meta-analysis to assess the effect of VT on physiology and clinical outcomes in OLV patients. Databases until February 2023 were retrieved from PubMed, Cochrane Library and Web of Science. Randomized controlled trials comparing the application of low and high VT ventilation in adults with OLV were performed. Demographic variables, VT, physiology, and clinical outcomes were retrieved. The random-effects model calculated the summary of odds ratios with 95% confidence intervals (CI) and mean difference with standard deviation. A total of 12 studies involving a total of 876 participants met the inclusion criteria. Low VT ventilation was associated with decreased risk of acute lung injury [relative risk 0.50, 95% CI (0.28, 0.88), P=0.02]. Low VT ventilation decreased the driving pressure (ΔP) and peak pressure (Ppeak) and improved arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2). Furthermore, the present study suggested that a significant difference in blood IL-6 was observed between low and high VT ventilation [mean difference, -35.51 pg/ml, 95% CI (-66.47, -4.54 pg/ml), P=0.02]. A decrease in the length of stay at the hospital occurred in the low VT group when set to 4-5 ml/kg. In the OLV patients, low VT ventilation decreased the risk of acute lung injury, blood IL-6, ΔP and Ppeak, and improved PaO2/FiO2. Furthermore, when low VT was set to 4-5 ml/kg, the length of stay at the hospital decreased.

Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression

BackgroundPulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia.MethodsSystematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables.ResultsWe selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46–63). The pooled AUC for the PPV was 0.77 (0.73–0.80), with a mean threshold of 10.8 (10.6–11.0). The pooled AUC for the SVV was 0.76 (0.72–0.80), with a mean threshold of 12.1 (11.6–12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40–62) and 57% (46–83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position.ConclusionThe overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability.Trial Registration: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120

Allometric scaling of metabolic rate and cardiorespiratory variables in aquatic and terrestrial mammals.

While basal metabolic rate (BMR) scales proportionally with body mass (Mb ), it remains unclear whether the relationship differs between mammals from aquatic and terrestrial habitats. We hypothesized that differences in BMR allometry would be reflected in similar differences in scaling of O2 delivery pathways through the cardiorespiratory system. We performed a comparative analysis of BMR across 63 mammalian species (20 aquatic, 43 terrestrial) with a Mb range from 10 kg to 5318 kg. Our results revealed elevated BMRs in small (>10 kg and <100 kg) aquatic mammals compared to small terrestrial mammals. The results demonstrated that minute ventilation, that is, tidal volume (VT )·breathing frequency (fR ), as well as cardiac output, that is, stroke volume·heart rate, do not differ between the two habitats. We found that the "aquatic breathing strategy", characterized by higher VT and lower fR resulting in a more effective gas exchange, and by elevated blood hemoglobin concentrations resulting in a higher volume of O2 for the same volume of blood, supported elevated metabolic requirements in aquatic mammals. The results from this study provide a possible explanation of how differences in gas exchange may serve energy demands in aquatic versus terrestrial mammals.

Midterm results of bipolar ablation in patients with intramural substrate and recurrent VTs based on a single center experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Catheter ablation of VTs and intramyocardial substrate (IS) remains a challenge that may require alternative mapping and ablation strategies such as bipolar ablation (BA) to achieve VT non inducibility. However, the long-term success of these alternative strategies is still uncertain. Purpose The aim of this study was to report the midterm center experience success of BA RF ablation of VT in patients with documented intramyocardial scar in cardiac imaging. Methods 19 patients with documented intramyocardial substrate on cardiac imaging (cardiac MRI or cardio CT with delayed enhancement) and VT recurrences after at least one conventional catheter ablation were retrospectively included. The intraprocedural success (i.e. VT non inducibility at the end of procedure) respectively midterm success (i.e VT recurrence after 6 months from BA) were investigated. The ablation was performed using a special RF generator which permits bipolar RF ablation between 2 irrigated catheters. Results A total number of 19 patients were included (100 % men, mean age 66,7 ± 9,16 y/o). The mean LVEF was 39,5 ± 5,7. The distribution of underlying structural heart disease was as follow: 21 % ischemic cardiomyopathy (4 out of 19 patients), 52 % dilative cardiomyopathy (10 out of 19 patients) respectively 26 % other etiologies (5 out of 19 patients). A mean number of 2 ± 1 conventional VT ablation were previously performed. In almost all patients (94 %, 18 out of 19 patients) the clinical VT was induced before the BA (mean CL 342 ± 91ms). The BA was performed predominantly septal (84%, 16 out of 19 patients). In 3 patients an endo/epicardial BA was performed. No VT was inducible any more at the end of procedure in 15 patients (79 %). At a mean follow up of 1 ± 0,5 years no recurrence of clinical VT was noted but non-clinical VT recurrence was seen in 9 patients (47 %) exclusively in patients with septal substrate. Conclusion BA represents a good alternative strategy for CA in patients with IS and failed conventional VT ablation with good acute success but high VT recurrence rate in patients with septal IS.

Deciphering the ZrO2 phase engineering effects on dry reforming of methane over the Ni/ZrO2 catalysts

The Ni/ZrO2 catalyst, with inexpensive price, high activity and excellent thermostability, has been widely investigated for dry reforming of methane (DRM). However, the stability of the catalyst still remains challenging due to the inevitable Ni sintering and carbon deposition under the high-temperature operation. Herein, the effects of the ZrO2 phase engineering in the Ni/ZrO2 catalyst on the DRM performance are highlighted. The characterization results reveal that the rising precipitated temperature can improve the tetragonal ratio (vt) in the catalysts using KOH as the precipitant and the catalyst with higher vt can be obtained via employing Na2CO3 or NaOH as the precipitant. The increased vt might be caused by the increased Ni content inserted into the ZrO2 support lattice. Ni dispersion is promoted with the raised vt resulting from the enhanced metal-support interaction. Besides, stronger acidity-basicity and more defects, including Zr3+ and surface oxygen species, are also detected on the catalyst with higher vt. Thus, the activity and stability over the Ni/ZrO2 catalysts displays a positive relation with the vt value. Especially, the conversions of CH4 and CO2 over the catalyst precipitated at 80 °C with NaOH as the precipitant are 80% ∼ 62% and 85% ∼ 72%, respectively, after evaluated for 3600 min with 4.3% carbon deposition. It has also been identified that the tetragonal ZrO2 plays a vital role in restraining carbon accumulation and graphitization. Furthermore, the infrared spectroscopy experiments illustrate that the reactive oxygen species are richer on the catalyst with higher vt and easier to react with CH4.

PO-05-058 PROGNOSTIC EVALUATION OF PATIENTS WITH ICD IN A LATIN AMERICAN TERTIARY CENTER.

Despite advances in ICD, SCD remains a public health problem. Chagas disease, still prevalent in Brazil, is associated with higher VT and VF events and SCD when compared to other cardiopathies. Data are conflicting in correlating mortality reduction in chagasic patients and the ICD implantation. We aimed to evaluate the ICD receivers mortality after structuring arrhythmia service in a Latin American tertiary center. Evaluate if the mortality and VT/VF events decrease when patients who received ICD at different periods of time (2007-2010, 2011-2014, 2015-2018) are compared in a tertiary center; compare the prognosis of chagasic to non-chagasic patients in different periods. Retrospective observational study of patients with ICD implanted in the Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG) between October 2007 and December 2018. The primary outcome was mortality, evaluated in the total sample and in each period. The secondary outcomes were the VT/VF events and the combined outcome of death and/or VT/VF, evaluated in the total sample and in each period. A total of 885 patients were included, 31% chagasic. Out of these, 254 (28%) died, 127 (14%) had VT/VF and 329 (37%) died and/or had VT/VF. The Kaplan-Meier curves showed that period 3 vs. 1 was the only variable associated with better death-free survival, p=0.007. For the VT/VF and the combined outcome free survival curves, Chagas disease was the only variable associated with higher rate of events; p<0.001 and p=0.009, respectively. In the cox's analysis adjusted for age, sex and Chagas, period 2 vs. 1 was protective for death (HR 0.715, 95%CI 0.539-0.948) and combined outcome (HR 0.713, 95%CI 0.537-0.945); period 3 vs. 1 was protective for death (HR 0.516, 95%CI 0.351-0.759) and combined outcome (HR 0.530, 95%CI 0.361-0.780). After adjusting for age and gender, Chagas was associated with VT/VF in periods 1 (HR 2.531, 95%CI 1.469-4.360) and 2 (HR 3.247, 95%CI 1.735-6.076). There was a gradual reduction in mortality and combined outcome for ICD receivers at periods 2011-2014 and 2015-2018 compared to the initial period 2007-2010. Chagas was associated with a higher VT/VF events in ICD receivers only in the first two periods. The improvement of results was concomitant with the incorporation of new modalities and technologies to treat patients with ICD. The better organization of care may be associated with reduction of overall mortality and arrhythmic events in this population.

Comparative study on traditional and new etchants for radon monitoring using Poly(allyl diglycol carbonate) (PADC) and identification of (Na3H(CO3)2.2H2O) in etched products

A comparative study is conducted on Traditional Etchants (NaOH/H2O, KOH/H2O) and New Etchants viz. NaOH/Methanol, NaOH/Ethanol and NaOH/1-propanol for Poly(allyl diglycol carbonate) (PADC) used in Radon monitoring. Molar concentration of traditional etchants NaOH/H2O and KOH/H2O is varied from 1 M to 6 M and etching temperature is varied from 30 °C to 80 °C to verify optimal etching parameter. Etching is done for 8 to 9.5 h in the steps of 30 min. An average bulk etch rate (Vb) of 1.4μm/h and 1.7μm/h for NaOH/H2O and KOH/H2O is calculated respectively under optimal etching conditions. Optimal reported concentrations of 1.5 M, 1.5 M and 1 M respectively, are used to make standard NaOH/Methanol, NaOH/Ethanol and NaOH/1-propanol solutions. Track densities, track diameters, bulk etch rate (Vb), track etch rate (Vt), etching time, variation in mass and thickness for both traditional and new etchants are calculated and compared. Traditional etchants take much longer time (5 to 7 h) for etching with initial swelling due to absorption of etchant on the surface of detector due to broken molecular chains, causing increase in mass and thickness of detectors for initial 0.5 to 1 h of etching which are measured with digital balance (±0.0001 g) and digital micrometer (±0.001 mm) respectively. New etchants take short time for etching (30 min approx.). There is no initial increase in mass and thickness of detectors due to short etching time and high Vb of new etchant. Traditional etchants give high track densities with low Vb and Vt while new etchants gives low track density with high Vb and Vt. New tracks formation is rare in new etchants as compared to traditional etchants. An average radon concentration level of 21.8 kBqm−3 is calculated from detectors etched in traditional etchants while new etchants do not provide any useful information about radon track density to calculate radon concentration for the given samples. Trona i-e Na3H(CO3)2.2H2O is identified as a common product formed in the etched products of PADC etched in either of the etchants i.e. traditional etchants and new etchants, using X-ray powder diffraction (XRPD) analysis.

RESPIRATORY MECHANICS AND NEURAL RESPIRATORY DRIVE OF UNTREATED GASPING DURING CARDIAC ARREST IN A PORCINE MODEL.

Introduction: Although the effects on hemodynamics of gasping during cardiac arrest (CA) have received a lot of attention, less is known about the respiratory mechanics and physiology of respiration in gasping. This study aimed to investigate the respiratory mechanics and neural respiratory drive of gasping during CA in a porcine model. Method: Pigs weighing 34.9 ± 5.7 kg were anesthetized intravenously. Ventricular fibrillation (VF) was electrically induced and untreated for 10 min. Mechanical ventilation (MV) was ceased immediately after the onset of VF. Hemodynamic and respiratory parameters, pressure signals, diaphragmatic electromyogram data, and blood gas analysis data were recorded. Results: Gasping was observed in all the animals at a significantly lower rate (2-5 gaps/min), with higher tidal volume ( VT ; 0.62 ± 0.19 L, P < 0.01), and with lower expired minute volume (2.51 ± 1.49 L/min, P < 0.001) in comparison with the baseline. The total respiratory cycle time and the expiratory time tended to be lengthened. Statistically significant elevations in transdiaphragmatic pressure, the pressure-time product of diaphragmatic pressure, and the mean of root mean square diaphragmatic electromyogram values (RMSmean) were observed ( P < 0.05, P < 0.05, and P < 0.001, respectively); however, VT /RMSmean and transdiaphragmatic pressure/RMSmean were reduced at all time points. The partial pressure of oxygen showed a continuous decline after VF to reach statistical significance in the 10th minute (9.46 ± 0.96 kPa, P < 0.001), whereas the partial pressure of carbon dioxide tended to first rise and then fall. Conclusions: Gasping during CA was characterized by high VT , extremely low frequency, and prolonged expiratory time, which may improve hypercapnia. During gasping, increased work of breathing and insufficient neuromechanical efficacy of neural respiratory drive suggested the necessity of MV and appropriate management strategies for MV during resuscitation after CA.

Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study

To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE). A single-center prospective physiologic study. At a single university medical center. Adult patients with severe COVID-19 ARDS on VV ECMO. Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP=1 cmH2O), and (5) 2 hours after returning to LDPV. Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p=0.481 and p=0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers. Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome

ObjectiveEvidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study. DesignA retrospective cohort study. SettingFive ICUs with their totally 130 beds in Taiwan. Patients or participantsARDS patients under invasive ventilation. InterventionsNo. Main variables of interest28-D mortality. ResultTotally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT=6.7ml/kg), intermediate (mean VT=8.9ml/kg) and high (mean VT=11.2ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P=0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P=0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n=66 for each group), their outcomes were also not significantly different. ConclusionIntermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Respiratory Mechanics and Gas Exchange in Acute Respiratory Distress Syndrome Associated with COVID-19

Aim. To compare respiratory mechanics and gas exchange in patients with acute respiratory distress syndrome (ARDS) with and without COVID-19.Material and methods. We examined 96 patients, who were divided into two groups. The main group included 48 patients with COVID-19-associated ARDS. The control group included 48 patients with ARDS not associated with COVID-19. Most characteristic patients were selected for the following baseline parameters: age, sex, SAPS II score, disease severity, plateau pressure (Pplateau), oxygenation index (PaO₂/FiO₂), and arterial-alveolar oxygen gradient (A-aO₂). Respiratory mechanics and gas exchange parameters assessed immediately after ARDS diagnosis and on days 1, 3 and 7 of treatment included arterial oxygen (PaO₂) and carbon dioxide (PaCO₂) pressure, tidal volume (Vt), respiratory rate (RR), respiratory minute volume (RMV), positive end expiratory pressure (PEEP), and Pplateau.Results. Patients in the main group had higher Vt (9.7 vs. 5.1 ml/kg, P&lt;0.001), RR (38 vs. 30 min-1, P&lt;0.001), and RMV (27.7 vs. 10.5 l/min, P&lt;0.001). Control group patients showed hypercapnia (PaCO₂ 43 vs. 38 mmHg, P&lt;0.001), lower respiratory compliance (30 vs. 48 ml/cm H₂O, P&lt;0.001) and ventilation ratio (VR) (1.5 vs. 2.0, P&lt;0.01). Lower PEEP values were required for patients in the main group. However, despite the higher rate of tracheal intubation in the control group (50% vs 16.7%) in the initial period of intensive care, the proportion of patients receiving invasive lung ventilation was significantly higher in the main group (33.3% vs.14.6%) by day 7.Conclusion. The initial phase (the first 7 days) of ARDS associated with COVID-19 is characterized by higher values of Vt, RR and RMV, as well as lung compliance vs «typical» ARDS with almost identical PaO₂/FiO₂ values.

This Month in Anesthesiology

This Month in Anesthesiology

Noise characterisation of GaN current aperture vertical electron transistor metal‐insulated semiconductor field effect transistor with Δ‐shaped gate for low noise radio frequency amplifiers

In this article, vertical CAVET with boron-doped GaN layer as current blocking layer (CBL) for AlGaN/GaN is proposed in this study, and different electrical characteristics of the devices, such as DC (Ids − Vds), small-signal radio frequency and high-frequency microwave noise performances, are characterised using Synopsys TCAD simulations. The vertical CAVET AlGaN/GaN metal-insulated semiconductor field effect transistor (MIS-HEMT) has been found to have a high threshold VT = 6.36 V, drain saturation current, Ids,sat = 3.41 kA/cm2, reduced OFF-state current <10−12 and improved high frequency and noise performances. The findings provide insight on noise sources and provide information on how to improve GaN transistor noise performance. Its useful characterisation tool for learning more about the imperfections in advanced AlGaN/GaN MIS-HEMTs and how they evolve. A two-port noise equivalent-circuit description is used to calculate data for noise. Using data from noise and scattering parameters that have been measured, we evaluated the effect of noise sources due to gate and drain, as well as their correlation. The devices exhibit a minimum noise figure (NFmin) and an equivalent noise resistance (Rn) of 1.21 dB and 20 Ω at 20 GHz, with Vgs = 5 V and Vds = 10 V, which is small and appropriate for low-noise amplifiers with a wide bandwidth. The maximum output power density Pout of 23 dBm and the maximum PAE of 63.3% are achieved for GaN V-shaped CAVET MIS-HEMTs with Vds = 10 V at 3.12 GHz is achieved. A comparison is made between the noise performance of conventional HEMTs, MIS-HEMTs and FETs. The methods for obtaining the noise figure (NFmin) and other noise metrics are then explained and compared with those found in the literature.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study

BackgroundThe impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. MethodsWe retrospectively recorded tidal volume (Vt; ml kg−1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg−1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg−1] or high [Vt >8 ml kg−1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. ResultsOverall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg−1; 95% confidence interval [CI], 1.35–1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O−1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0–0.5] at 41.2 ml cm H2O−1 compliance, compared with 5.8% [95% CI, 3.8–7.8] at 14 ml cm H2O−1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O−1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). ConclusionsThe association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Role of Mitophagy-based TLR9 Signal Pathway in Neonatal Ventilator-induced Lung Injury

The study focused on the role of mitophagy in neonatal ventilator-induced lung injury (VILI). Immunoassays were used to study the TLR9 signaling pathway of neonatal VILI, expected to provide a feasible solution for neonatal VILI. The mice were randomly divided into four groups, group A: spontaneous breathing group; group B: normal tidal volume (VT) group (VT=9mL/kg); group C: high VT group (VT=39mL/kg); and group D: ODN2088 (400μg/ Only) intervention + high VT group. The four groups were compared for the expression of inflammatory factors. It was found that as the culture time increased, the expression of TLR9, MyD88, and NF-κBp65 in the lung tissue of the large VT group was significantly higher than those in the spontaneous breathing group and normal VT group, and the differences were statistically significant; and TLR9 inhibitors could activate the TLR9-MyD88 signaling pathway to up-regulate the expression of NF-κB, mediating the release of inflammatory factors to cause VILI.

Intermediate tidal volume is an acceptable option for ventilated patients with acute respiratory distress syndrome.

ObjectiveEvidence only proves low surpasses high tidal volume (VT) for acute respiratory distress syndrome (ARDS). Intermediate VT is a common setting for ARDS patients and has been demonstrated as effective as low VT in non-ARDS patients. The effectiveness of intermediate VT in ARDS has not been studied and is the objective of this study.DesignA retrospective cohort study.SettingFive ICUs with their totally 130 beds in Taiwan.Patients or participantsARDS patients under invasive ventilation.InterventionsNo.Main variables of interest28-D mortality.ResultTotally 382 patients, with 6958 ventilator settings eligible for lung protection, were classified into low (mean VT = 6.7 ml/kg), intermediate (mean VT = 8.9 ml/kg) and high (mean VT = 11.2 ml/kg) VT groups. With similar baseline ARDS and ICU severities, intermediate and low VT groups did not differ in 28-D mortality (47% vs. 63%, P = 0.06) or other outcomes such as 90-D mortality, ventilator-free days, ventilator-dependence rate. Multivariate analysis revealed high VT was independently associated with 28-D and 90-D mortality, but intermediate VT was not significantly associated with 28-D mortality (HR 1.34, CI 0.92–1.97, P = 0.13) or 90-D mortality. When the intermediate and low VT groups were matched in propensity scores (n = 66 for each group), their outcomes were also not significantly different.ConclusionIntermediate VT, with its outcomes similar to small VT, is an acceptable option for ventilated ARDS patients. This conclusion needs verification through clinical trials.

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury.

Background and Objective: Lung-protective mechanical ventilation is known to attenuate ventilator-associated lung injury (VALI), but often at the expense of hypoventilation and hypercapnia. It remains unclear whether the main mechanism by which VALI is attenuated is a product of limiting mechanical forces to the lung during ventilation, or a direct biological effect of hypercapnia. Methods: Acute lung injury (ALI) was induced in 60 anesthetized rats by the instillation of 1.25 M HCl into the lungs via tracheostomy. Ten rats each were randomly assigned to one of six experimental groups and ventilated for 4 h with: 1) Conventional HighV E Normocapnia (high VT, high minute ventilation, normocapnia), 2) Conventional Normocapnia (high VT, normocapnia), 3) Protective Normocapnia (VT 8 ml/kg, high RR), 4) Conventional iCO 2 Hypercapnia (high VT, low RR, inhaled CO2), 5) Protective iCO 2 Hypercapnia (VT 8 ml/kg, high RR, added CO2), 6) Protective endogenous Hypercapnia (VT 8 ml/kg, low RR). Blood gasses, broncho-alveolar lavage fluid (BALF), and tissue specimens were collected and analyzed for histologic and biologic lung injury assessment. Results: Mild ALI was achieved in all groups characterized by a decreased mean PaO2/FiO2 ratio from 428 to 242 mmHg (p < 0.05), and an increased mean elastance from 2.46 to 4.32 cmH2O/L (p < 0.0001). There were no differences in gas exchange among groups. Wet-to-dry ratios and formation of hyaline membranes were significantly lower in low VT groups compared to conventional tidal volumes. Hypercapnia reduced diffuse alveolar damage and IL-6 levels in the BALF, which was also true when CO2 was added to conventional VT. In low VT groups, hypercapnia did not induce any further protective effect except increasing pulmonary IL-10 in the BALF. No differences in lung injury were observed when hypercapnia was induced by adding CO2 or decreasing minute ventilation, although permissive hypercapnia decreased the pH significantly and decreased liver histologic injury. Conclusion: Our findings suggest that low tidal volume ventilation likely attenuates VALI by limiting mechanical damage to the lung, while hypercapnia attenuates VALI by limiting pro-inflammatory and biochemical mechanisms of injury. When combined, both lung-protective ventilation and hypercapnia have the potential to exert an synergistic effect for the prevention of VALI.

In vivo imaging translocator protein (TSPO) in autism spectrum disorder.

Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [18F]FEPPA PET. Data from 13 typically developing control participants with matching age and TSPO rs6971 polymorphism (9 F, age 24 ± 5 years) were chosen from previous studies for comparison. The two tissue compartment model (2TCM) was used to determine the total volume of distribution ([18F]FEPPA VT) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [18F]FEPPA VT relative to controls (F(1,26)= 1.74, p = 0.20). However, 2 ASD participants with higher VT had concurrent major depressive episodes (MDE), which has been consistently reported during MDE. After excluding those 2 ASD participants, in a post-hoc analysis, our results show lower [18F]FEPPA VT in ASD participants compared to controls (F(1,24)= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.

Elevated PaCO2 levels increase pulmonary artery pressure.

Permissive hypercapnia is commonly used in mechanically ventilated patients to avoid lung injury but its effect on pulmonary artery pressure (PAP) is still unclear, particularly in combination with tidal volume (Vt). Therefore, an in vivo study was performed on adult rabbits ventilated with low (9 ml/Kg, LVt group) or high (15 ml/Kg, HVt group) tidal volume (Vt) and alterations in PAP were estimated. Both groups of animals initially were ventilated with FiO2 0.3 (Normocapnia-1) followed by inhalation of enriched CO2 gas mixture (FiCO2 0.10) to develop hypercapnia (Hypercapnia-1). After 30 min of hypercapnia, animals were re-ventilated with FiO2 0.3 to develop normocapnia (Normocapnia-2) again and then with FiCO2 0.10 to develop hypercapnia (Hypercapnia-2). Systolic, diastolic and mean PAP were assessed with a catheter in the pulmonary artery. In HP-1 and HP-2, PaCO2 increased (p < 0.0001) in both LVt and HVt animals compared to baseline values. pH decreased to ≈7.2 in HP-1 and ≈7.1 in HP -2. In normocapnia, the rise in Vt from 9 to 15 ml/Kg induced an increase in static compliance (Cstat), plateau airway pressure (Pplat) and PAP. Hypercapnia increased PAP in either LVt or HVt animals without significant effect on Cstat or Pplat. A two-way ANOVA revealed that there was not a statistically significant interaction between the effects of hypercapnia and tidal volume on mPAP (p = 0.76). In conclusion, increased Vt per se induced an increase in Cstat, Pplat and PAP in normocapnia. Hypercapnia increased PAP in rabbits ventilated with low or high Vt but this effect was not long-lasting.