NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

Although gastroesophageal reflux disease (GERD), a common chronic disease in clinical practice, has been widely studied, its potential adverse impact on patients is still a significant clinical concern. It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism. The pathogenesis of GERD is diverse and complex. As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients, new treatment options need to be explored. Our previous study suggested that the activation of nuclear factor-kappa beta (NF-κB) in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux. Based on the literature and our previous study results, it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier. NF-κB may play an important role in the development of GERD. This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD, in order to provide new strategies for the treatment of GERD.

Effect of Anesthetics on Functional Connectivity of Developing Brain.

The potential anesthetic neurotoxicity on the neonate is an important focus of research investigation in the field of pediatric anesthesiology. It is essential to understand how these anesthetics may affect the development and growth of neonatal immature and vulnerable brains. Functional magnetic resonance imaging (fMRI) has suggested that using anesthetics result in reduced functional connectivity may consider as core sequence for the neurotoxicity and neurodegenerative changes in the developed brain. Anesthetics either directly impact the primary structures and functions of the brain or indirectly alter the hemodynamic parameters that contribute to cerebral blood flow (CBF) in neonatal patients. We hypothesis that anesthetic agents may either decrease the brain functional connectivity in neonatal patients or animals, which was observed by fMRI. This review will summarize the effect and mechanism of anesthesia on the rapid growth and development infant and neonate brain with fMRI through functional connectivity. It is possible to provide the new mechanism of neuronal injury induced by anesthetics and objective imaging evidence in animal developing brain.

Association between dyslipidemia and risk of type 2 diabetes mellitus in middle-aged and older Chinese adults: a secondary analysis of a nationwide cohort.

AIMS: To evaluate the type 2 diabetes mellitus (T2DM) risk of individuals with different types of dyslipidaemia and compare the predictive value of distinct lipid parameters in predicting T2DM. METHODS: We conducted a secondary analysis of data from the China Health and Retirement Longitudinal Study (CHARLS). 17 708 individuals over 45 years old were interviewed, and 11 847 blood samples were collected at the baseline survey (2011-2012). Outcome of T2DM was confirmed during two follow-up surveys (2013-2014 and 2015-2016). The HRs and 95% CI of T2DM associated with dyslipidaemia were estimated by Cox proportional hazards regressions model. The discriminatory value of eight lipid parameters were compared by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 7329 participants were enrolled in our analysis; during the mean follow-up time of 3.4 years, 387 (5.28%) participants developed new-onset diabetes. Compared with participants in normal lipid levels, the T2DM risk of those with hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol (HDL-C) were significantly increased (HRs (95% CI) were 1.48 (1.11 to 1.96), 1.92 (1.49 to 2.46) and 1.67 (1.35 to 2.07), respectively). The AUCs of non-HDL-C (0.685, 95% CI 0.659 to 0.711), triglyceride (TG) (0.684, 95% CI 0.658 to 0.710), total cholesterol (TC)/HDL-C (0.685, 95% CI 0.659 to 0.712) and TG/HDL-C (0.680, 95% CI 0.654 to 0.706) were significantly (p<0.005) larger than that of other lipid parameters. CONCLUSION: Middle-aged and elderly adults with hypertriglyceridaemia, hypercholesterolaemia and low HDL-C were at higher risk for developing diabetes. Non-HDL-C, TG, TC/HDL and TG/HDL have greater performance than other lipid parameters in predicting T2DM incidence.

Successful Anesthesia Management in a Patient With Type A Aortic Dissection Complicated by Renal Failure and Suspected Coronavirus Disease.

Stanford type A acute aortic dissection (AAD) is a life-threatening illness that presents with chest pain and hemodynamic instability. AAD prompt and accurate evaluation and management are critical for survival as it is a cardiac surgical emergency. The initial treatment of AAD mandates strict blood pressure stabilization with intravenous antihypertensive medications. The progressive nature of the disease will increase the mortality as time elapses between diagnosis and surgical intervention. In addition, the patient's blood pressure control is challenged in the presence of renal failure requiring hemodialysis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or named 2019-nCoV) pneumonia was a newly underrecognized illness (COVID-19 [coronavirus disease 2019]). COVID-19 can cause severe acute respiratory distress syndrome, acute kidney injury, heart injury, and liver dysfunction, which would aggravate the progress of aortic dissection. In this article, we report the successful anesthesia management in a pneumonia patient with AAD complicated with renal failure during the COVID-19 epidemic period, who underwent emergency surgery and deep hypothermic circulatory arrest repair.

Risk Stratification and Optimization to Prevent Right Heart Failure During Left Ventricular Assist Device Implantation.

Left ventricular assist device (LVAD) implantation results in superior survival rates compared with optimal medical therapy in patients with end-stage heart failure. However, a potential complication of LVAD implantation is right heart failure (RHF), which can be devastating. Therefore, identifying preoperative risk factors for RHF and optimal management for these patients are critical for ensuring favorable postoperative outcomes. This review focuses on methods of assessing the risk factors for RHF before surgery, including evaluation of biomarkers, echocardiography, hemodynamics, risk-scoring systems, and existing conditions of right heart dysfunction. In addition, the review also explores the perioperative strategic approaches to reducing the likelihood of RHF.

Coronary angiography or not after cardiac arrest without ST segment elevation: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to review the available evidence and evaluate the necessity of immediate coronary angiography (CAG) to obtain positive outcomes for out-of-hospital cardiac arrest (OHCA) patients without ST segment elevation. DATA SOURCES: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases. STUDY SELECTION: We included observational and case-control studies of outcomes among individuals without ST segment elevation experiencing OHCA who had immediate, delayed, or no CAG. DATA EXTRACTION: We extracted study details, as well as patient characteristics and outcomes. DATA SYNTHESIS: Six studies (n = 2665) investigating mortality until discharge demonstrated a significant increase in survival benefit with early CAG (odds ratio [OR] = 1.78; 95%CI = 1.51-2.11; I = 81%; P < .0001). Seven studies (n = 2909) showed a significant preservation of neurological functions with early CAG at discharge (OR = 1.66; 95%CI = 1.37-2.02; P < .00001). Four studies (n = 1357) investigating survival outcomes with middle-term follow-up revealed no significant benefit with early CAG (OR = 1.21; 95%CI = 0.93-1.57; I = 66%; P = .15). CONCLUSIONS: Our meta-analysis demonstrates that there may be significant benefits in performing immediate CAG on patients who experience OHCA without ST segment elevation.

Statement From the Society for the Advancement of Transplant Anesthesia: White Paper Advocating Desirable Milestones and Competencies for Anesthesiology Fellowship Training in the Field of Lung Transplantation.

The clinical, educational, and research facets of lung transplantation have advanced significantly since the first lung transplant in 1963. The formation of the International Society for Heart and Lung Transplantation (ISHLT) and subsequent Registry has forged a precedent of collaborative teamwork that has significantly affected current lung transplantation outcomes. The Society for the Advancement of Anesthesia (SATA) is dedicated to developing educational platforms for all facets of transplant anesthesia. Additionally, we believe that the anesthetic training for lung transplantation has not kept pace with other advances in the field. As such, SATA presents for consideration these educational milestones and competencies for anesthetic fellowship training in the field of lung transplantation. The proposed milestones were designed on the framework of 6 core competencies created by the Accreditation Council on Graduate Medical Education. The milestones were identified by combining the expert opinion of our Thoracic Transplant Committee, our experience as educators, and literature review. We offer this White Paper to the anesthesiology and transplant communities as a starting point for the discussion and evolution of perioperative anesthetic care in the field of lung transplantation.

Fluid Overload in Special Pediatric Cohorts With Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Following Surgical Repair.

OBJECTIVE: To investigate the prevalence, risk factors, and clinical outcomes associated with early fluid overload (FO) in a special group of pediatric patients undergoing repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). DESIGN: It was a retrospective study performed with multiple variable regression analysis. SETTING: A single cardiac surgical institution. PARTICIPANTS: Eighty-eight patients younger than 18 years of age undergoing ALCAPA surgical repair with cardiopulmonary bypass were recruited at the authors' institution from June 2010 to September 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Of 88 pediatric patients with ALCAPA after surgical repair, 37.5% developed early FO, defined as fluid accumulation ≥5% within the period from surgery until midnight of postoperative day 1. Patients with early FO were younger, weighed less, and had worse preoperative cardiac dysfunction. With logistic regression analysis, being underweight was confirmed to be a risk factor for FO development (odds ratio, 8.66; 95% confidence interval, 2.83-26.52; p < 0.001). Early FO also predicted severe acute kidney injury, respiratory morbidity, and low cardiac output syndrome after reimplantation procedure. Patients with early FO also had significantly longer mechanical ventilation hours (p  <  0.001), intensive care unit length of stay (p = 0.003), and hospital length of stay (p = 0.009). CONCLUSION: Early FO ≥5% has been linked to adverse postoperative outcomes in pediatric patients undergoing repair for ALCAPA. The use of restrictive fluid management is crucial for patients who have lower weight and poor myocardial function before and after complex surgical procedures such as in ALCAPA settings.

Epidemiology of acute kidney injury among paediatric patients after repair of anomalous origin of the left coronary artery from the pulmonary artery.

OBJECTIVES: Acute kidney injury (AKI) is a prevalent complication after the surgical repair of paediatric cardiac defects and is associated with poor outcomes. Insufficient renal perfusion secondary to severe myocardial dysfunction in neonates is most likely an independent risk factor in patients undergoing repair for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). We retrospectively investigated the epidemiology and outcomes of children with ALCAPA who developed AKI after repair. METHODS: Eighty-nine children underwent left coronary reimplantation. The paediatric-modified risk, injury, failure, loss and end-stage (p-RIFLE) criteria were used to diagnose AKI. RESULTS: The incidence of AKI was 67.4% (60/89) in our study. Among the patient cohort with AKI, 23 (38.3%) were diagnosed with acute kidney injury/failure (I/F) (20 with acute kidney injury and 3 with acute kidney failure). Poor cardiac function (left ventricular ejection fraction < 35%) prior to surgery was a significant contributing factor associated with the onset of AKI [odds ratio (OR) 5.55, 95% confidential interval (CI) 1.39-22.13; P = 0.015], while a longer duration from diagnosis to surgical repair (OR 0.97, 95% CI 0.95-1.00; P = 0.049) and a higher preoperative albumin level (OR 0.83, 95% CI 0.70-0.99; P = 0.041) were found to lower the risk of AKI. Neither the severity of preoperative mitral regurgitation nor mitral annuloplasty was associated with the onset of AKI. After reimplantation, there was 1 death in the no-AKI group and 2 deaths in the AKI/F group (P = 0.356); the remaining patients survived until hospital discharge. The median follow-up time was 46.5 months (34.0-63.25). During follow-up, patients in the AKI cohort were seen more often by specialists and reassessed more often by echocardiography. CONCLUSIONS: Paediatric AKI after ALCAPA repair occurs at a relatively higher incidence than that suggested by previous reports and is linked to poor clinical outcomes. Preoperative cardiac dysfunction (left ventricular ejection fraction < 35%) is strongly associated with AKI. The beneficial effect of delaying surgery seen in some of our cases warrants further investigation, as it is not concordant with standard teaching regarding the timing of surgery for ALCAPA.

Levosimendan for Pediatric Anomalous Left Coronary Artery From the Pulmonary Artery Undergoing Repair: A Single-Center Experience.

Objectives: Our aim was to retrospectively evaluate the benefit of levosimendan in certain complicated congenital heart procedures such as the pediatric anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) with moderate or severe cardiac dysfunction and its repair. Study Design: We enrolled 40 pediatric patients with ALCAPA and moderate or severe left ventricular dysfunction. Patients who had a preoperative left ventricular ejection fraction (LVEF) of 50% or less and had undergone the surgical correction of their coronary artery through cardiopulmonary bypass met the criteria of our study. Twenty patients were given 0.1-0.2 µg/kg/min levosimendan at the induction of anesthesia, which lasted for 24 h. The remaining 20 patients were not given levosimendan. Results: The mean preoperative LVEF in the levosimendan group was significantly lower than that in the non-levosimendan group (22.5 ± 10.7% vs. 31.8 ± 8.1%, p = 0.004). On postoperative day 7, the LVEF in the levosimendan group was still significantly lower (27.1 ± 8.9% vs. 37.5 ± 11.0%, p = 0.002). There was no significant difference in ΔLVEF detected on day 7 [median 30.8%, interquartile range (IQR) -4.4 to 63.5% vs. median 15.1%, IQR -3.5 to 40.0%, p = 0.560] or at follow-up of about 180 days (median 123.5%, IQR 56.1-222.6% vs. median 80.0%, IQR 36.4-131.3%, p = 0.064). There was no significant difference between the two groups in postoperative vasoactive-inotropic score (VIS) at any of the time points of 1, 6, 12, 24, and 48 h (p = 0.093). Three patients had to be supported by extracorporeal membrane oxygenation when difficulty appeared in weaning off cardiopulmonary bypass because of low cardiac output in the non-levosimendan group, but no patient needed extracorporeal membrane oxygenation after levosimendan infusion (p = 0.231). The length of intensive care unit stay (median 10.5 days, IQR 7.3-39.3 days vs. median 4.0 days, IQR 2.0-10.0 days, p = 0.002) and duration of mechanical ventilation (median 146.0 h, IQR 76.5-888.0 h vs. median 27.0 h, IQR 11.0-75.0 h, p = 0.002) were revealed to be longer in the levosimendan group. Peritoneal dialysis occurred in eight patients (40%) in the levosimendan group and two patients (10%) in the non-levosimendan group (p = 0.028). No significant difference was revealed in all-cause mortality within 180 days, which occurred in two patients (10%) in the levosimendan group and one (5%) in the non-levosimendan group (p = 1.00). Conclusion: Levosimendan's unique pharmacological properties have strong potential for cardiac function recovery among pediatric patients with ALCAPA with impaired left ventricular function who have undergone surgical repair.However, any improvement from levosimendan on postoperative outcomes or mortality was not substantiated by this study and must be investigated further.

Microbial Fermentation of Organic Carbon Substrates Drives Rapid pH Neutralization and Element Removal in Bauxite Residue Leachate.

Globally, mineral processing activities produce an estimated 680 GL/yr of alkaline wastewater. Neutralizing pH and removing dissolved elements are the main goals of wastewater treatment prior to discharge. Here, we present the first study to explicitly evaluate the role of microbial communities in driving pH neutralization and element removal in alkaline wastewaters by fermentation of organic carbon, using bauxite residue leachate as a model system, and evaluate the effects of organic carbon complexity and microbial inoculum addition rates on the performance of these treatment systems at laboratory scale. Rates and extents of pH neutralization were higher in bioreactors fed with simpler organic carbon substrates (glucose and banana: 6 days to reach pH ≤ 8) than those fed with more complex organic carbon substrates (eucalyptus mulch: 15 days to reach pH ≤ 8; woodchips: equilibrium pH around 9). Concentrations of dissolved Al, As, B, Mo, Na, S, and V all significantly decreased after bioremediation. Increasing soil inoculant addition rate accelerated rates and extent of pH neutralization and element removal up to 0.1 wt %; further increases had little effect. Overall, glucose added at 1.8 wt % and soil inoculum added at 0.1 wt % provided the most effective minimal combination of carbon substrate and inoculum to drive pH neutralization and element removal.

Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest.

BACKGROUND: Levosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats. METHODS: Animals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10 µg/kg) supplemented with levosimendan (bolus 12 µg/kg and infusion for 1 h, EL group); epinephrine only (10 µg/kg, E group), or levosimendan only (bolus 12 µg/kg and infusion for 1 h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded. RESULTS: 10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation (P < 0.001); among them, 10, 4, and 2 rats survived at the end of a 60-min observation period from each group, respectively (P = 0.001). The coronary perfusion pressure in the EL group was higher than that of either the E or L group (P < 0.05). The lung wet-to-dry weight ratio and rate of damaged alveoli were lower in the EL group than the E group (P < 0.05). CONCLUSIONS: In the early stage of resuscitation for asphyxia-induced cardiac arrest in rats, levosimendan supplemented with epinephrine can significantly increase coronary perfusion pressure, reduce lung injury, and ultimately enhance the survival rate.

Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment.

Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities.

Pulmonary Venous Diastolic Flow Reversal and Flash Pulmonary Edema During Management of Ongoing Myocardial Ischemia with Intraaortic Balloon Pump.

A 65-year-old man was admitted for acute coronary syndrome with depressed left ventricular function and moderate aortic regurgitation. He was managed with an intraaortic balloon pump for circulatory support before coronary artery bypass grafting and subsequently developed flash pulmonary edema with an associated rare finding of diastolic pulmonary venous flow reversal. In this report, we provide a review of intraaortic balloon pump use in current clinical practice and elaborate on the pathophysiology of an uncommon pulmonary venous flow pattern found in our patient.