Extracellular vesicles of the liver fluke Opisthorchis felineus stimulate the angiogenesis of human umbilical vein endothelial cells.

The liver fluke Opisthorchis felineus is a clinically important food-borne parasite of humans. Infection with O. felineus in mammals is associated with liver morbidities such as periductal fibrosis, bile duct neoplasia, and chronic inflammation. Previously we have shown that excretory-secretory products (ESP) can stimulate the healing of skin wounds in mice, which may be due to stimulated angiogenesis and extracellular matrix remodeling. However, there are no studies analyzing the angiogenic character of O. felineus, and its effects on angiogenesis, vascularity, and vascular endothelium. The aim of this study was to evaluate the capacity of ESP and extracellular vesicles (EVs) of O. felineus to stimulate angiogenesis and the formation of pseudo-capillaries in vitro. We also aimed at the assessment of the angiogenesis during the infection in vivo, and estimation of the endothelial cell type abundances from heterogeneous bulk liver transcriptome between uninfected and infected animals with single-cell information. The study revealed significant alterations in vascularity in the hamster liver and significant involvement of portal endothelial cells at the transcriptome level. We also demonstrated that the ESP and EVs of O. felineus have the capacity to stimulate the formation of pseudo-capillaries in vitro. Both ESP and EVs appeared to have similar effects on all four parameters, increasing node formation and total master segments length, and significantly decreasing total isolated branches length and number of isolated segments of pseudo-capillaries. The liver flukes manipulate the host's angiogenic response, a fact that has been related to the pathogenesis caused by these parasites. Understanding these pathogenic mechanisms may uncover new therapeutic targets to relieve or prevent the most severe complications of opisthorchiasis.

Myocardial protection with phosphocreatine in high-risk cardiac surgery patients: a randomized trial.

BACKGROUND: This study was conducted to test the hypothesis that phosphocreatine (PCr), administered intravenously and as cardioplegia adjuvant in patients undergoing cardiac surgery with prolonged aortic cross clamping and cardiopulmonary bypass (CPB) time, would decrease troponin I concentration after surgery. METHODS: In this randomized, double-blind, placebo-controlled pilot study we included 120 patients undergoing double/triple valve repair/replacement under cardiopulmonary bypass in the cardiac surgery department of a tertiary hospital. The treatment group received: intravenous administration of 2 g of PCr after anesthesia induction; 2.5 g of PCr in every 1 L of cardioplegic solution (concentration = 10 mmol/L); intravenous administration of 2 g of PCr immediately after heart recovery following aorta declamping; 4 g of PCr at intensive care unit admission. The control group received an equivolume dose of normosaline. RESULTS: The primary endpoint was peak concentration of troponin I after surgery. Secondary endpoints included peak concentration of serum creatinine, need for, and dosage of inotropic support, number of defibrillations after aortic declamping, incidence of arrhythmias, duration of Intensive Care Unit (ICU) stay, length of hospitalization. There was no difference in peak troponin I concentration after surgery (PCr, 10,508 pg/ml [IQR 6,838-19,034]; placebo, 11,328 pg/ml [IQR 7.660-22.894]; p = 0.24). There were also no differences in median peak serum creatinine (PCr, 100 µmol/L [IQR 85.0-117.0]; placebo, 99.5 µmol/L [IQR 90.0-117.0]; p = 0.87), the number of patients on vasopressor/inotropic agents (PCr, 49 [88%]; placebo, 57 [91%]; p = 0.60), the inotropic score on postoperative day 1 (PCr, 4.0 (0-7); placebo, 4.0 (0-10); p = 0.47), mean SOFA score on postoperative day 1 (PCr, 5.25 ± 2.33; placebo, 5,45 ± 2,65; p = 0.83), need for defibrillation after declamping of aorta (PCr, 22 [39%]; placebo, 25 [40%]; p = 0.9),, duration of ICU stay and length of hospitalization as well as 30-day mortality (PCr, 0 (0%); placebo,1 (4.3%); p = 0.4). CONCLUSION: PCr administration to patients undergoing double/triple valve surgery under cardiopulmonary bypass is safe but is not associated with a decrease in troponin I concentration. Phosphocreatine had no beneficial effect on clinical outcomes after surgery. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the Identifier: NCT02757443. First posted (published): 02/05/2016.

Proteomic characterization of Opisthorchis felineus exosome-like vesicles and their uptake by human cholangiocytes.

The epidemiologically important food-borne trematode Opisthorchis felineus infests the liver biliary tract of fish-eating mammals and causes disorders, including bile duct neoplasia. Many parasitic species release extracellular vesicles (EVs) that mediate host-parasite interaction. Currently, there is no information on O. felineus EVs. Using gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry, we aimed to characterize the proteome of EVs released by the adult O. felineus liver fluke. Differential abundance of proteins between whole adult worms and EVs was assessed by semiquantitative iBAQ (intensity-based absolute quantification). Imaging, flow cytometry, inhibitor assays, and colocalization assays were performed to monitor the uptake of the EVs by H69 human cholangiocytes. The proteomic analysis reliably identified 168 proteins (at least two peptides matched a protein). Among major proteins of EVs were ferritin, tetraspanin CD63, helminth defense molecule 1, globin 3, saposin B type domain-containing protein, 60S ribosomal protein, glutathione S-transferase GST28, tubulin, and thioredoxin peroxidase. Moreover, as compared to the whole adult worm, EVs proved to be enriched with tetraspanin CD63, saposin B, helminth defense molecule 1, and Golgi-associated plant pathogenesis-related protein 1 (GAPR1). We showed that EVs are internalized by human H69 cholangiocytes via clathrin-dependent endocytosis, whereas phagocytosis and caveolin-dependent endocytosis do not play a substantial role in this process. Our study describes for the first time proteomes and differential abundance of proteins in whole adult O. felineus worms and EVs released by this food-borne trematode. Studies elucidating the regulatory role of individual components of EVs of liver flukes should be continued to determine which components of EV cargo play the most important part in the pathogenesis of fluke infection and in a closely linked pathology: bile duct neoplasia. SIGNIFICANCE: The food-borne trematode Opisthorchis felineus is a pathogen that causes hepatobiliary disorders in humans and animals. Our study describes for the first time the release of EVs by the liver fluke O. felineus, their microscopic and proteomic characterization, and internalization pathways by human cholangiocytes. Differential abundance of proteins between whole adult worms and EVs was assessed. EVs are enriched with canonical EV markers as well as parasite specific proteins, i.e. tetraspanin CD63, saposin B, helminth defense molecule 1, and others. Our findings will form the basis of the search for potential immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases, as well as novel vaccine candidates.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and while European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. MATERIALS AND METHODOLOGY: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. RESULTS: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: In these international guidelines, ERS, ESICM, ESCMID and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

PURPOSE: Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. METHODS: The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. RESULTS: Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. CONCLUSIONS: In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR. OBJECTIVES: To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databases on 1 June 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment, or no treatment for people with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. We excluded studies that used anti-VEGFs in people undergoing vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participants were women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was 8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR, and participants in 11 studies had high-risk PDR (HRPDR). Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The mean number of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding of interventions and outcome assessors. A few studies had selective reporting and attrition bias. No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA compared with PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I2 = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm2, 95% CI -6.84 to -1.43; I2 = 75%; 4 RCTS, 189 eyes; low-certainty evidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I2 = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I2 = 0%; 6 RCTS, 1008 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67, 95% CI 0.49 to 0.93; I2 = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the quality of life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I2 = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not know if anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differences in visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up (< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone. The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates. AUTHORS' CONCLUSIONS: Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.

Enhanced THz radiation through a thick plasmonic electrode grating photoconductive antenna with tight photocarrier confinement.

We propose the design of a photoconductive antenna (PCA) emitter with a plasmonic grating featuring a very high plasmonic Au electrode with a thickness of 170 nm. As we show numerically, the increase in h significantly changes the electric field distribution, owing to the excitation of higher-order plasmon guided modes in the Au slit waveguides, leading to an additional increase in the emitted THz power. We develop the plasmonic grating geometry with respect to maximal transmission of the incident optical light, so as to expect the excitation of higher-order plasmon guided Au modes. The fabricated PCA can efficiently work with low-power laser excitation, demonstrating an overall THz power of 5.3 µW over an ∼4.0 THz bandwidth, corresponding to a conversion efficiency of 0.2%. We believe that our design can be used to meet the demands of modern THz spectroscopic and high-speed imaging applications.

Feasibility of concomitant left atrial appendage closure and percutaneous coronary intervention in patients with acute coronary syndrome and atrial fibrillation: a randomized pilot study.

The optimal approach for prevention of cardiovascular events and reduction of bleeding in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) is still controversial. The aim of our study is to asses our single-center experience with concomitant left atrial appendage occlusion (LAAO) and percutaneous coronary intervention (PCI). 50 patients with ACS without ST elevation and history of AF were randomized after successful PCI to LAAO or conventional medical therapy. The primary endpoints were safety and length of hospitalization. The follow-up period was 30 days. The mean procedural times were 113 ± 23 min PCI + LAAO implantation and 39 ± 19 min of PCI only (p < 0.001), while mean fluoroscopy times were 18 ± 8 min and 12 ± 8 min (p < 0.001), respectively. No procedure-related complications were observed. There was no difference observed for length of hospitalization between two groups. LAAO in patients with ACS and AF undergoing PCI appears safe.

Topological Insulator Films for Terahertz Photonics.

We discuss experimental and theoretical studies of the generation of the third terahertz (THz) frequency harmonic in thin films of Bi2Se3 and Bi2-xSbxTe3-ySey (BSTS) topological insulators (TIs) and the generation of THz radiation in photoconductive antennas based on the TI films. The experimental results, supported by the developed kinetic theory of third harmonic generation, show that the frequency conversion in TIs is highly efficient because of the linear energy spectrum of the surface carriers and fast energy dissipation. In particular, the dependence of the third harmonic field on the pump field remains cubic up to the pump fields of 100 kV/cm. The generation of THz radiation in TI-based antennas is obtained and described for the pump, with the energy of photons corresponding to the electron transitions to higher conduction bands. Our findings open up possibilities for advancing TI-based films into THz photonics as efficient THz wave generators and frequency converters.

Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Effect of volatile anesthetics on myocardial infarction after coronary artery surgery: a post hoc analysis of a randomized trial

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. Measurements and main Results: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Residual Lesion Diagnostics in Pediatric Postcardiotomy Extracorporeal Membrane Oxygenation and Its Outcomes.

BACKGROUND: To assess the impact of diagnostic procedures in identifying residual lesions during extracorporeal membrane oxygenation (ECMO) on survival after pediatric cardiac surgery. METHODS: Between January 2012 and December 2017, 74 patients required postcardiotomy ECMO. Patients were retrospectively divided into 2 groups: Group I underwent only echocardiography ([echo only] 46 patients, 62.2%) and group II (echo+) underwent additional diagnostic tests (ie, computed tomography [CT] or cardiac catheterization; 28 patients, 37.8%). Propensity score matching was used to balance the 2 groups by baseline characteristics. RESULTS: Two equal groups (28 patients in each group) were formed by propensity score matching. Fourteen (50%) patients in the echo-only group and 20 (71%) patients in the echo+ group were successfully weaned from ECMO (P = .17). Four (14.3%) patients survived in the echo-only group and 15 (53.5%) patients survived in the echo+ group (P = .004). Patients in the echo+ group had a lower chance of dying compared to the echo-only group (odds ratio, 0.14.6; 95% CI, 0.039-0.52; P = .003). The residual lesions, which may have served as a mortality factor, were found by autopsy in 8 (40%) patients in the echo-only group, while none were found in the echo+ group (P = .014). CONCLUSIONS: The autopsies of patients who died despite postcardiotomy ECMO support showed that in 40% of cases that had been investigated by echo only, residual lesions that had not been detected by echocardiography were present. The cardiac catheterization and CT during ECMO are effective and safe for identifying residual lesions. Early detection and repair of residual lesions may increase the survival rate of pediatric cardiac patients on ECMO.

Calcium administration In patients undergoing CardiAc suRgery under cardiopulmonary bypasS (ICARUS trial): Rationale and design of a randomized controlled trial.

INTRODUCTION: Weaning from cardiopulmonary bypass (CPB) is a critical step of any cardiac surgical procedure and often requires pharmacologic intervention. Calcium ions are pivotal elements for the excitation-contraction coupling process of cardiac myocytes. Thus, calcium administration might be helpful during weaning from CPB. METHODS: We describe a multicenter, placebo-controlled, double blind randomized clinical trial to assess the effect of calcium chloride on the need for inotropic support among adult patients during weaning from CPB. The experimental group (409 patients) will receive 15 mg/kg of calcium chloride. The control group (409 patients) will receive an equivalent volume of 0.9% sodium chloride. Both drugs will be administered intravenously as a bolus at the beginning of weaning from CPB. RESULTS: The primary outcome will be the need for inotropic support between termination of CPB and completion of surgery. Secondary outcomes will be: duration of inotropic support, vasoactive-inotropic score 30 min after transfer to intensive care unit and on postoperative day 1, plasma alpha-amylase on postoperative day 1, plasma Ca2+ concentration immediately before and 10-15 min after calcium chloride administration, non-fatal myocardial infarction, blood loss on postoperative day 1, need for transfusion of red blood cells, signs of myocardial ischemia on electrocardiogram after arrival to intensive care unit, all-cause mortality at 30 days or during hospital stay if this is longer than 30 days. DISCUSSION: This trial is designed to assess whether intravenous calcium chloride administration could reduce the need for inotropic support after cardiopulmonary bypass weaning among adults undergoing cardiac surgery.

The relationship between global cardiac and regional left atrial sympathetic innervation and epicardial fat in patients with atrial fibrillation.

AIM: To investigate the relationship between epicardial adipose tissue (EAT) volume and distribution and the parameters of global cardiac and regional left atrial (LA) sympathetic activity in patients with atrial fibrillation (AF). METHODS AND RESULTS: The data of the 45 consecutive patients scheduled for an index catheter ablation (CA) for AF were analyzed. Total and peri-atrial EAT volumes were measured by cardiac CT. Parameters of global cardiac sympathetic activity and discrete sympathetic regions around LA were assessed by 123I-mIBG SPECT/CT. The patients were followed up for AF recurrences assessment during 12 months after CA. A total of 133 (mean per patient 2.96 ± 1.07) discrete 123I-mIBG uptake areas (DUAs), corresponding to typical anatomical locations of LA ganglionated plexi (GP), were identified. Peri-atrial EAT volume was associated with the number of DUAs (regression estimate, 5.1 [95% CI, 0.3-9.9], p = 0.03). There was no statistically significant association between either total or peri-atrial EAT volumes and risks of AF recurrence. The washout rate (WR) was associated with reduced risk of AF recurrence (HR = 0.95; 95% CI 0.92-0.99; p = 0.01), while left ventricular (LV) myocardium 123I-mIBG summed defect score (SDS) was linked to increased hazards of AF recurrence (HR = 1.04; 95% CI 1.01-1.08; p = 0.03). CONCLUSION: Peri-atrial EAT volume is associated with regions of sympathetic activity corresponding to typical anatomical locations of LA GP. The WR was associated with reduced risk of AF recurrence while LV myocardial SDS was linked to increased hazards of AF recurrence.

Effect of intraoperative dexamethasone on major complications and mortality among infants undergoing cardiac surgery The DECISION Randomized Clinical Trial

IMPORTANCE Corticosteroids are widely used in pediatric cardiac surgery to blunt systemic inflammatory response and to reduce complications; nevertheless, their clinical efficacy is uncertain. OBJECTIVE To determine whether intraoperative administration of dexamethasone is more effective than placebo for reducing major complications and mortality during pediatric cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS The Intraoperative Dexamethasone in Pediatric Cardiac Surgery was an investigator-initiated, double-blind, multicenter randomized trial that involved 4 centers in China, Brazil, and Russia. A total of 394 infants younger than 12 months, undergoing cardiac surgery with cardiopulmonary bypass were enrolled from December 2015 to October 2018, with follow-up completed in November 2018. INTERVENTIONS The dexamethasone group (n = 194) received 1mg/kg of dexamethasone; the control group (n = 200) received an equivolume of 0.9%sodium chloride intravenously after anesthesia induction. MAIN OUTCOMES AND MEASURES The primary end pointwas a composite of death, nonfatalmyocardial infarction, need for extracorporeal membrane oxygenation, need for cardiopulmonary resuscitation, acute kidney injury, prolonged mechanical ventilation, or neurological complications within 30 days after surgery. There were 17 secondary end points, including the individual components of the primary end point, and duration of mechanical ventilation, inotropic index, intensive care unit stay, readmission to intensive care unit, and length of hospitalization. RESULTS All of the 394 patients randomized (median age, 6 months; 47.2%boys) completed the trial. The primary end point occurred in 74 patients (38.1%) in the dexamethasone group vs 91 patients (45.5%) in the control group (absolute risk reduction, 7.4%; 95%CI, −0.8%to 15.3%; hazard ratio, 0.82; 95%CI, 0.60 to 1.10; P = .20). Of the 17 prespecified secondary end points, none showed a statistically significant difference between groups. Infections occurred in 4 patients (2.0%) in the dexamethasone group vs 3 patients (1.5%) in the control group. CONCLUSIONS AND RELEVANCE Among infants younger than 12 months undergoing cardiac surgery with cardiopulmonary bypass, intraoperative administration of dexamethasone, compared with placebo, did not significantly reduce major complications and mortality at 30 days. However, the study may have been underpowered to detect a clinically important difference.