Effects of transcutaneous electrical nerve stimulation on myocardial protection in patients undergoing aortic valve replacement: a randomized clinical trial

Abstract Background Cardiopulmonary bypass-related myocardial ischemia-reperfusion injury is a major contributor to postoperative morbidity. Although transcutaneous electrical nerve stimulation (TENS) has been found to have cardioprotective effects in animal studies and healthy volunteers, its effects on cardiac surgery under cardiopulmonary bypass patients have not been evaluated. We investigated the effects of TENS on myocardial protection in patients undergoing aortic valve replacement surgery using cardiopulmonary bypass. Methods Thirty patients were randomized to receive TENS or sham in three different anesthetic states – pre-anesthesia, sevoflurane, or propofol (each n = 5). TENS was applied with a pulse width of 385 μs and a frequency of 10 Hz using two surface electrodes at the upper arm for 30 min. Sham treatment was provided without stimulation. The primary outcome was the difference in myocardial infarct size following ischemia-reperfusion injury in rat hearts perfused with pre- and post-TENS plasma dialysate obtained from the patients using Langendorff perfusion system. The cardioprotective effects of TENS were determined by assessing reduction in infarct size following treatment. Results There were no differences in myocardial infarct size between pre- and post-treatment in any group (41.4 ± 4.3% vs. 36.7 ± 5.3%, 39.8 ± 7.3% vs. 27.8 ± 12.0%, and 41.6 ± 2.2% vs. 37.8 ± 7.6%; p = 0.080, 0.152, and 0.353 in the pre-anesthesia, sevoflurane, and propofol groups, respectively). Conclusions In our study, TENS did not show a cardioprotective effect in patients undergoing aortic valve replacement surgery. Trial registration This study was registered at clinicaltrials.gov ( NCT03859115 , on March 1, 2019)

Intraoperative mild hyperoxia may be associated with improved survival after off-pump coronary artery bypass grafting: a retrospective observational study

Background : The effect of hyperoxia due to supplemental oxygen administration on postoperative outcomes in patients undergoing cardiac surgery remains unclear. This retrospective study aimed to evaluate the relationship between intraoperative oxygen tension and mortality after off-pump coronary artery bypass grafting (OPCAB). Methods : The study included adult patients who underwent isolated OPCAB between July 2010 and June 2020. Patients were categorised into three groups based on their intraoperative time-weighted average arterial oxygen partial pressure (PaO2): normoxia/near-normoxia ( 250 mmHg). The risk of in-hospital mortality was compared using weighted logistic regression analysis. Restricted cubic spline analysis was performed to analyse intraoperative PaO2 as a continuous variable. The risk of cumulative all-cause mortality was compared using Cox regression analysis. Results : The normoxia/near-normoxia, mild hyperoxia, and severe hyperoxia groups included 229, 991, and 173 patients (n = 1393), respectively. The mild hyperoxia group had a significantly lower risk of in-hospital mortality than the normoxia/near-normoxia (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.06–0.22) and severe hyperoxia groups (OR, 0.06; 95% CI, 0.03–0.14). Intraoperative PaO2 exhibited a U-shaped relationship with in-hospital mortality in the non-hypoxic range. The risk of cumulative all-cause mortality was significantly lower in the mild hyperoxia group (hazard ratio, 0.72; 95% CI, 0.52–0.99) than in the normoxia/near-normoxia group. Conclusions : Maintaining intraoperative PaO2 at 150–250 mmHg was associated with a lower risk of mortality after OPCAB than PaO2 at 250 mmHg. Future randomised trials are required to confirm if mildly increasing arterial oxygen tension during OPCAB to 150–250 mmHg improves postoperative outcomes

Super-hydration and reduction of manganese oxide minerals at shallow terrestrial depths

Manganese oxides are ubiquitous marine minerals which are redox sensitive. As major components of manganese nodules found on the ocean floor, birnessite and buserite have been known to be two distinct water-containing minerals with manganese octahedral interlayer separations of similar to 7 angstrom and similar to 10 angstrom, respectively. We show here that buserite is a super-hydrated birnessite formed near 5 km depth conditions. As one of the most hydrous minerals containing ca. 34.5 wt. % water, super-hydrated birnessite, i.e., buserite, remains stable up to ca. 70 km depth conditions, where it transforms into manganite by releasing ca. 24.3 wt. % water. Subsequent transformations to hausmannite and pyrochroite occur near 100 km and 120 km depths, respectively, concomitant with a progressive reduction of Mn4+ to Mn2+. Our work forwards an abiotic geochemical cycle of manganese minerals in subduction and/or other aqueous terrestrial environments, with implications for water storage and cycling, and the redox capacity of the region

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial

Background To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). Methods This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. Results A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83–1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18–3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). Conclusions In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019)

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy respons

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Modeling the Effect of Cell Variation on the Performance of a Lithium-Ion Battery Module

Owing to the variation between lithium-ion battery (LIB) cells, early discharge termination and overdischarge can occur when cells are coupled in series or parallel, thereby triggering a decrease in LIB module performance and safety. This study provides a modeling approach that considers the effect of cell variation on the performance of LIB modules in energy storage applications for improving the reliability of the power quality of energy storage devices and efficiency of the energy system. Ohm’s law and the law of conservation of charge were employed as the governing equations to estimate the discharge behavior of a single strand composing of two LIB cells connected in parallel based on the polarization properties of the electrode. Using the modeling parameters of a single strand, the particle swarm optimization algorithm was adopted to predict the discharge capacity and internal resistance distribution of 14 strands connected in series. Based on the model of the LIB strand to predict the discharge behavior, the effect of cell variation on the deviation of the discharge termination voltage and depth of discharge imbalance was modeled. The validity of the model was confirmed by comparing the experimental data with the modeling results

Reversible Intramolecular P–S Bond Formation Coupled with a Ni(0)/Ni(II) Redox Process

P–S bond formation/cleavage mediated by a nickel ion supported by a PPP ligand (PPP = P­[2-P^<i>i</i>Pr₂-C₆H₄]₂^–) has been investigated herein. To gain an entry into this chemistry, a mononuclear thiolato nickel complex, (PPP)­Ni­(SAr) (<b>1a</b>,<b>b</b>) was prepared by treating the chloride starting material with NaSPh. Upon carbonylation, this complex produces a nickel(0) monocarbonyl species, (PP^SArP)­Ni­(CO) (<b>2a</b>,<b>b</b>), in which the thiolate migrates onto the central P of the ligand to give a P–S bond and two-electron reduction of a nickel­(II) center. The reaction undergoes via a pseudo-first-order decay with respect to consumption of a nickel­(II) thiolato species, suggesting an intramolecular reaction under the excess CO­(g) conditions. The reverse reaction involving P–S bond cleavage with concomitant decarbonylation occurs to regenerate <b>1a</b>,<b>b</b> in benzene. Reaction of <b>2a</b> with trityl chloride results in Ph₃CSPh formation, whereas the reaction with MeI gives methylation at a phosphide moiety or a thiolate group

Reversible Intramolecular P–S Bond Formation Coupled with a Ni(0)/Ni(II) Redox Process

P–S bond formation/cleavage mediated by a nickel ion supported by a PPP ligand (PPP = P­[2-P^<i>i</i>Pr₂-C₆H₄]₂^–) has been investigated herein. To gain an entry into this chemistry, a mononuclear thiolato nickel complex, (PPP)­Ni­(SAr) (<b>1a</b>,<b>b</b>) was prepared by treating the chloride starting material with NaSPh. Upon carbonylation, this complex produces a nickel(0) monocarbonyl species, (PP^SArP)­Ni­(CO) (<b>2a</b>,<b>b</b>), in which the thiolate migrates onto the central P of the ligand to give a P–S bond and two-electron reduction of a nickel­(II) center. The reaction undergoes via a pseudo-first-order decay with respect to consumption of a nickel­(II) thiolato species, suggesting an intramolecular reaction under the excess CO­(g) conditions. The reverse reaction involving P–S bond cleavage with concomitant decarbonylation occurs to regenerate <b>1a</b>,<b>b</b> in benzene. Reaction of <b>2a</b> with trityl chloride results in Ph₃CSPh formation, whereas the reaction with MeI gives methylation at a phosphide moiety or a thiolate group