The protocol of enhanced recovery after cardiac surgery in adult patients: A stepped wedge cluster randomized trial.

BACKGROUND: The enhanced recovery after cardiac surgery is a bundle of measurements from preoperative to postoperative phases to improve patients' recovery. METHODS: This study is a multicenter, stepwise design, cluster randomized controlled trial. About 3,600 patients presenting during control and intervention periods are eligible if they are aged from 18 to 80 years old awaiting elective cardiac surgery with cardiopulmonary bypass (CPB). About 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive ERAS strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). DISCUSSION: This study aims to compare the application of ERAS management protocol and traditional management protocol in adult cardiac surgery under extracorporeal circulation.

The protocol of Enhanced Recovery After Cardiac Surgery (ERACS) in congenital heart disease: a stepped wedge cluster randomized trial.

BACKGROUND: The Enhanced Recovery After Cardiac Surgery (ERACS) programs are comprehensive multidisciplinary interventions to improve patients' recovery. The application of the ERAS principle in pediatric patients has not been identified completely. METHODS: This study is a multicenter, stepwise design, cluster randomized controlled trial. 3030 patients presenting during control and intervention periods are eligible if they are aged from 28 days to 6 years old and awaiting elective correction surgery of congenital heart disease with cardiopulmonary bypass. 5 centers are randomly assigned to staggered start dates for one-way crossover from the control phase to the intervention phase. In the intervention periods, patients will receive a bundle strategy including preoperative, intraoperative, and postoperative approaches. During the control phase, patients receive the usual care. The primary outcome consists of major adverse cardiac and cerebrovascular events (MACCEs), postoperative pulmonary complications (PPCs), and acute kidney injury (AKI). DISCUSSION: This study aims to explore whether the bundle of ERAS measurements could improve patients' recovery in congenital heart surgery. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . (NCT05914103).

Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant because it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who had cardiac surgery were identified from 2 publicly available clinical registries: the Medical Information Mart for Intensive Care III (MIMIC-III) and the eICU Collaborative Research Database (eICU). EXPOSURE: Administration of acetaminophen in the first 48 hours after surgery. OUTCOME: Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria. ANALYTICAL APPROACH: Multivariable cause-specific hazards regression analysis. RESULTS: We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these 2 cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a lower risk of severe AKI in both the MIMIC-III (adjusted hazard ratio [AHR], 0.86 [95% CI, 0.79-0.94]) and eICU (AHR, 0.84 [95% CI, 0.72-0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses. LIMITATIONS: No data on acetaminophen dose. CONCLUSIONS: Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI. PLAIN-LANGUAGE SUMMARY: There is uncertainty about whether antioxidant medications such as acetaminophen may protect against kidney injury. Therefore, we evaluated the associations between acetaminophen use and kidney outcomes in adults recovering from cardiac surgery in 2 large clinical registries. Acetaminophen treatment was significantly associated with a 14%-16% lower risk of severe and any-stage acute kidney injury but similar risks of kidney replacement therapy and in-hospital mortality. Our findings suggest that acetaminophen use may protect against kidney injury in adult patients recovering from cardiac surgery.

A simple-to-use nomogram for predicting prolonged mechanical ventilation for children after Ebstein anomaly corrective surgery: a retrospective cohort study.

BACKGROUND: Prolonged mechanical ventilation (PMV) after pediatric cardiac surgery imposes a great burden on patients in terms of morbidity, mortality as well as financial costs. Ebstein anomaly (EA) is a rare congenital heart disease, and few studies have been conducted about PMV in this condition. This study aimed to establish a simple-to-use nomogram to predict the risk of PMV for EA children. METHODS: The retrospective study included patients under 18 years who underwent corrective surgeries for EA from January 2009 to November 2021. PMV was defined as postoperative mechanical ventilation time longer than 24 hours. Through multivariable logistic regression, we identified and integrated the risk factors to develop a simple-to-use nomogram of PMV for EA children and internally validated it by bootstrapping. The calibration and discriminative ability of the nomogram were determined by calibration curve, Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) curve. RESULTS: Two hundred seventeen children were included in our study of which 44 (20.3%) were in the PMV group. After multivariable regression, we obtained five risk factors of PMV. The odds ratios and 95% confidence intervals (CI) were as follows: preoperative blood oxygen saturation, 0.876(0.805,0.953); cardiothoracic ratio, 3.007(1.107,8.169); Carpentier type, 4.644(2.065,10.445); cardiopulmonary bypass time, 1.014(1.005,1.023) and postoperative central venous pressure, 1.166(1.016,1.339). We integrated the five risk factors into a nomogram to predict the risk of PMV. The area under ROC curve of nomogram was 0.805 (95% CI, 0.725,0.885) and it also provided a good discriminative information with the corresponding Hosmer-Lemeshow p values > 0.05. CONCLUSIONS: We developed a nomogram by integrating five independent risk factors. The nomogram is a practical tool to early identify children at high-risk for PMV after EA corrective surgery.

Effect of hemoglobin and oxygen saturation on adverse outcomes in children with tetralogy of fallot: a retrospective observational study.

BACKGROUND: Tetralogy of Fallot (TOF) is a common cyanotic congenital heart malformation that carries a high risk of right-to-left shunting. Anemia is characterized by decreased hemoglobin (Hb) levels that can affect tissue oxygen delivery and impact postoperative recovery in patients. Chronic hypoxia caused by right-to-left shunting of TOF could lead to compensatory increases in Hb to maintain systemic oxygen balance. This study aims to investigate whether preoperative Hb and blood oxygen saturation (SpO2) can predict adverse outcomes in children undergoing corrective surgery for TOF. METHODS: This retrospective study included patients under 18 years of age who underwent corrective surgery for TOF at Fuwai Hospital between January 2016 and December 2018. Adverse outcomes, including in-hospital death, extracorporeal membrane oxygenation implantation, ICU stay > 30 days, and severe complications, were considered as the primary outcome. Univariable and multivariable logistic analyses were performed to identify independent risk factors for adverse outcomes. Propensity score-matched (PSM) analysis was also conducted to minimize the confounding factors. RESULTS: A total of 596 children were included in the study, of which 64 (10.7%) experienced adverse outcomes. Hb*SpO2 < aaHb was identified as an independent risk factor for adverse outcomes (OR = 2.241, 95% CI = 1.276-3.934, P = 0.005) after univariable and multivariable logistic analyses. PSM analysis further confirmed the association between Hb*SpO2 < aaHb and adverse outcomes. Patients with Hb*SpO2 < aaHb had a significantly higher incidence of postoperative adverse outcomes, longer time of mechanical ventilation, and hospital stay, as well as higher in-hospital costs. CONCLUSIONS: Hb*SpO2 < aaHb is significantly associated with adverse outcomes in children undergoing corrective surgery for TOF. Clinicians can use this parameter to early identify high-risk children and optimize their postoperative management.

Suppression of Myocardial Hypoxia-Inducible Factor-1α Compromises Metabolic Adaptation and Impairs Cardiac Function in Patients With Cyanotic Congenital Heart Disease During Puberty.

BACKGROUND: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. METHODS: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. RESULTS: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. CONCLUSIONS: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.

Male bias in ACE2 basic science research: missed opportunity for discovery in the time of COVID-19.

Throughout the world, including the United States, men have worse outcomes from COVID-19 than women. SARS-CoV-2, the causative virus of the COVID-19 pandemic, uses angiotensin-converting enzyme 2 (ACE2) to gain cellular entry. ACE2 is a member of the renin-angiotensin system (RAS) and plays an important role in counteracting the harmful effects mediated by the angiotensin type 1 receptor. Therefore, we conducted Ovid MEDLINE and Embase database searches of basic science studies investigating the impact of the biological variable of sex on ACE2 expression and regulation from 2000, the year ACE2 was discovered, through December 31, 2020. Out of 2,131 publications, we identified 853 original research articles on ACE2 conducted in primary cells, tissues, and/or whole mammals excluding humans. The majority (68.7%) of these studies that cited the sex of the animal were conducted in males, while 11.2% were conducted solely in females; 9.26% compared ACE2 between the sexes, while 10.8% did not report the sex of the animals used. General findings are that sex differences are tissue-specific and when present, are dependent upon gonadal state. Renal, cardiac, and adipose ACE2 is increased in both sexes under experimental conditions that model co-morbidities associated with worse COVID-19 outcomes including hypertension, obesity, and renal and cardiovascular diseases; however, ACE2 protein was generally higher in the males. Studies in Ace2 knockout mice indicate ACE2 plays a greater role in protecting the female from developing hypertension than the male. Studying the biological variable of sex in ACE2 research provides an opportunity for discovery in conditions involving RAS dysfunction and will shed light on sex differences in COVID-19 severity.

The Angiotensin Type 1 Receptor Antagonist Losartan Prevents Ovariectomy-Induced Cognitive Dysfunction and Anxiety-Like Behavior in Long Evans Rats.

Women who have bilateral oophorectomies prior to the age of natural menopause are at increased risk of developing mild cognitive decline, dementia, anxiety, and depressive type disorders. Clinical and animal studies indicate angiotensin type 1 receptor (AT1R) blockers (ARBs) have blood pressure (BP)-independent neuroprotective effects. To investigate the potential use of ARBs in normotensive women at increased risk of developing neurocognitive problems, we studied a rat model of bilateral oophorectomy. Long Evans rats were sham-operated (Sham) or ovariectomized (Ovx) at 3 months of age and immediately treated continuously with vehicle (Veh) or the ARB losartan (Los) for the duration of the experiment. In contrast to many hypertensive rat models, ovariectomy did not increase mean arterial pressure (MAP) in these normotensive rats. Ovariectomized rats spent less time in the open arms of the elevated plus maze (EPM) [(% total time): Veh, 34.1 ± 5.1 vs. Ovx, 18.7 ± 4.4; p < 0.05] and in the center of the open field (OF) [(s): Veh, 11.1 ± 1.7 vs. Ovx, 6.64 ± 1.1; p < 0.05]. They also had worse performance in the novel object recognition (NOR) test as evidenced by a reduction in the recognition index [Veh, 0.62 ± 0.04 vs. Ovx, 0.45 ± 0.03; p < 0.05]. These adverse effects of ovariectomy were prevented by Los. Losartan also reduced plasma corticosterone in Ovx rats compared to Veh treatment [(ng/mL): Ovx-Veh, 238 ± 20 vs. Ovx-Los, 119 ± 42; p < 0.05]. Ovariectomy increased AT1R mRNA expression in the CA3 region of the hippocampus (Hc) [(copies x 106/µg RNA): Sham-Veh, 7.15 ± 0.87 vs. Ovx-Veh, 9.86 ± 1.7; p < 0.05]. These findings suggest the neuroprotective effects of this ARB in normotensive Ovx rats involve reduction of plasma corticosterone and blockade of increased AT1R activity in the hippocampus. These data suggest ARBs have therapeutic potential for normotensive women at increased risk of developing cognitive and behavioral dysfunction due to bilateral oophorectomy prior to the natural age of menopause.

Short-term very low caloric intake causes endothelial dysfunction and increased susceptibility to cardiac arrhythmias and pathology in male rats.

NEW FINDINGS: What is the central question of this study? What are the effects of a 2 week period of severe food restriction on vascular reactivity of resistance arteries and on cardiac structure and function? What is the main finding and its importance? This study showed, for the first time, that a 2 week period of severe food restriction in adult male Fischer rats caused endothelial dysfunction in mesenteric arteries and increased the susceptibility to ischaemia-reperfusion-induced arrhythmias and cardiac pathology. Our findings might have ramifications for cardiovascular risk in people who experience periods of inadequate caloric intake. ABSTRACT: Severe food restriction (sFR) is a common dieting strategy for rapid weight loss. Male Fischer rats were maintained on a control (CT) or sFR (40% of CT food intake) diet for 14 days to mimic low-calorie crash diets. The sFR diet reduced body weight by 16%. Haematocrits were elevated by 10% in the sFR rats, which was consistent with the reduced plasma volume. Mesenteric arteries from sFR rats had increased sensitivity to vasoconstrictors, including angiotensin II [maximum (%): CT, 1.30 ± 0.46 versus sFR, 11.5 ± 1.6; P < 0.0001; n = 7] and phenylephrine [maximum (%): CT, 78.5 ± 2.8 versus sFR, 94.5 ± 1.7; P < 0.001; n = 7] and reduced sensitivity to the vasodilator acetylcholine [EC50 (nm): CT, 49.2 ± 5.2 versus sFR, 71.6 ± 6.8; P < 0.05; n = 7]. Isolated hearts from sFR rats had a 1.7-fold increase in the rate of cardiac arrhythmias in response to ischaemia-reperfusion and more cardiac pathology, including myofibrillar disarray with contractions and cardiomyocyte lysis, than hearts from CT rats. The sFR dietary regimen is similar to very low-calorie commercial and self-help weight-loss programmes, which provide ∼800-1000 kcal day-1 . Therefore, these findings in rats warrant the study of cardiovascular function in individuals who engage in extreme dieting or are subjected to bouts of very low caloric intake for other reasons, such as socioeconomic factors and natural disasters.

Risk Factors for Prolonged Mechanical Ventilation After Total Cavopulmonary Connection Surgery: 8 Years of Experience at Fuwai Hospital.

OBJECTIVE: Prolonged mechanical ventilation (PMV) is closely associated with higher morbidity and mortality after total cavopulmonary surgery. The aim of the present study was to identify the clinical risk factors for PMV. DESIGN: A retrospective case-control study. SETTING: Fuwai Hospital. PARTICIPANTS: The study comprised 504 patients who underwent total cavopulmonary surgery from 2010 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The definition of PMV was derived from the Cox regression model for predicting postoperative length of hospital stay. Least absolute shrinkage and selection operator regression, logistic regression, and Cox regression were applied to identify predictors for PMV. Patients with mechanical ventilation time >9 hours were identified as having PMV. Independent predictors of PMV included age, intraoperative maximum vasoactive-inotropic score, minimal temperature during cardiopulmonary bypass, postoperative prothrombin time, alkaline phosphatase and total bilirubin levels, and postoperative fluid balance. These predictors also were achieved in the Cox regression for predicting the duration of mechanical ventilation. Patients with PMV were associated with increased blood transfusions, more consumption of vasopressin and antipulmonary hypertension medication, higher incidence of reintubation, more renal replacement treatment, longer intensive care unit stay, greater hospitalization costs, and more specialist visits. CONCLUSIONS: Age at surgery, maximal vasoactive-inotropic score and minimal temperature during cardiopulmonary bypass, postoperative prothrombin time, alkaline phosphatase and total bilirubin levels, and postoperative fluid balance were demonstrated to be independent predictors of PMV. Adopting a comprehensive strategy of perioperative management that targets the identified risk factors might significantly lower the risk of PMV and improve in-hospital outcomes, and furthermore, patients with PMV might need more specialist visits.

Renal T cell infiltration occurs despite attenuation of development of hypertension with hydralazine in Envigo's female Dahl rat maintained on a low-Na+ diet.

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg-1·day-1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group (n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group (n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.

A Propensity-Score Matched Analysis on Outcomes Using Recombinant Activated Factor VII in Pediatric Cardiac Surgery.

OBJECTIVE: To evaluate the effect of recombinant activated factor VII (rFVIIa) administration on outcomes in pediatric cardiac surgery patients with postoperative bleeding. DESIGN: A propensity score-matched retrospective study. SETTING: Single tertiary medical center. PARTICIPANTS: The study comprised 151 patients who received treatment with rFVIIa and were matched with control patients at a 1:2 ratio. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoints were thrombotic events, renal replacement therapy (RRT), and mortality. The secondary endpoints were length of intensive care unit stay and the reexploration rate. Patients in the rFVIIa group showed no significant differences in thrombotic events (odds ratio [OR] 1.03; 95% confidence interval [CI] 0.48-2.21; p = 0.948), mortality (OR 0.94; 95% CI 0.42-2.13; p = 0.891), and RRT (OR 1.38; 95% CI 0.73-2.58; p = 0.319). However, patients in the rFVIIa group experienced a prolonged length of intensive care unit stay (5.65 [3.00-12.28] d v 3.91 [1.83-6.77] d) and an increased reexploration rate (8.2% v 3.1%). High-dose rFVIIa was an independent risk factor of thrombotic events (OR 5.17; 95% CI 1.19-22.49; p = 0.029). CONCLUSION: This study found that rFVIIa is not associated with increased risks of postoperative thrombotic events, mortality, or RRT in pediatric patients undergoing cardiac surgery. Nevertheless, rFVIIa was associated with longer intensive care unit stay and increased reexploration rate. Furthermore, the risk for thrombotic events may increase with high-dose rFVIIa.

Salt-sensitive (Rapp) rats from Envigo spontaneously develop accelerated hypertension independent of ovariectomy on a low-sodium diet.

Inbred salt-sensitive (SS) rats developed by John Rapp and distributed by Harlan (SS/JrHsd) were shown to model ovariectomy-induced hypertension because on a low-sodium (LS) diet, ovariectomized SS (SS-OVX) animals became hypertensive in contrast to their sham-operated (SS-SHAM) normotensive littermates. After Harlan merged with Envigo in 2015, inconsistencies in the LS normotensive phenotype were reported. To further investigate these inconsistencies, we studied the effects of ovariectomy on SS and salt-resistant (SR) rats purchased from Envigo (SS/JrHsd/Env) between 2015 and 2017. The mean arterial pressure (MAP) in SS rats on a LS diet exceeded 160 mmHg at 7 mo old. Ovariectomy at 3 mo had no detectable effect on MAP from 4 to 7 mo, nor did ovariectomy at 1.5 mo significantly affect MAP at 10 mo in either strain; only strain differences in MAP were observed [MAP: SR-SHAM ( n = 7 rats), 102 ± 3 mmHg; SR-OVX ( n = 6 rats), 114 ± 1 mmHg; SS-SHAM ( n = 7 rats), 177 ± 6 mmHg; SS-OVX ( n = 5 rats), 190 ± 12 mmHg; where P < 0.0001 vs. SR, same ovarian-status for SS-SHAM and SS-OVX, respectively]. Whole genome sequencing revealed more genomic variants of SS/JrHsd/Env, including single nucleotide and insertion deletion polymorphisms and higher heterozygous/homozygous ratios compared with the reference genome, than for SS/JrHsd/Mcwi and SS/Jr rats maintained in Milwaukee, WI and Toledo, OH, respectively, and which still exhibit normal blood pressure on a LS diet. These findings demonstrate that the female SS/JrHsd/Env rat has genetically diverged from the original phenotype, which was normotensive on a LS diet when the ovaries were intact but rapidly developed hypertension when the ovaries were removed. Nonetheless, the SS/JrHsd/Env rat could be a valuable model that complements other animal models of spontaneous hypertension used to investigate mechanisms of essential hypertension.

Predictors of Short-term Outcomes Following Repair of Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery in Chinese Children: A Case-Control Study.

OBJECTIVE: To analyze the predictive factors associated with prolonged mechanical ventilation (PMV) and prolonged duration of inotropic support (PDIS) following anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) surgery with possible concomitant mitral valve procedure (MVP) in a relatively young population. DESIGN: A retrospective case-control study. SETTING: Fuwai hospital. PARTICIPANTS: Pediatric patients with ALCAPA surgery from July 2010 to October 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PMV was defined as a mechanical ventilation time ≥48 hours and PDIS as a duration of inotropic support ≥6 days. Univariate analysis, logistic regression analysis, and receiver operating characteristic curve analysis were used to identify independent predictors of PMV and PDIS. The independent predictors of PMV were found to be the left ventricular end-diastolic diameter z-score (LVEDDz), estimate of glomerular filtration rate (eGFR) and maximum vasoactive-inotropic score (VISm). The odds ratios and 95% confidence intervals for these predictors of PMV were the following: LVEDDz, 1.58 (1.19-2.09); eGFR, 0.96 (0.93-0.998); and VISm, 1.08 (1.01-1.17). The predictor of PDIS was LVEDDz at 1.65 (1.26-2.15). One patient died during hospitalization, and there was no reoperation. Thirty-seven patients received concomitant MVP with no hospital mortality. At discharge, mitral regurgitation (MR) had improved in all patients with MR. Patients with PMV were associated with more acute kidney injury, PDIS, and longer ICU and hospital stays. CONCLUSIONS: In relatively young individuals who received ALCAPA surgery and possible concomitant MVP, short-term outcomes are favorable. Based on their experience bias, the authors recommend combining LVEDDz, eGFR, and VISm to predict PMV and applying LVEDDz for PDIS.

Stretch Could Reduce Hamstring Injury Risk During Sprinting by Right Shifting the Length-Torque Curve.

Ruan, M, Li, L, Chen, C, and Wu, X. Stretch could reduce hamstring injury risk during sprinting by right shifting the length-torque curve. J Strength Cond Res 32(8): 2190-2198, 2018-It was hypothesized that static stretch would shift the length-torque curve to the right, which may reduce the risk of muscle strain injuries. The purpose of this study was to evaluate the acute effects of static stretching of hamstring (SSH) on the risk of hamstring injury during sprinting indicated by the shift of the length-torque relationship. Twelve female college athletes (age: 20.8 ± 0.7 years; height: 1.61 ± 0.05 m; body mass: 54.25 ± 4.22 kg) participated in this study. Subjects performed overground sprinting under 2 conditions: after warm-up with 4 × 30 seconds SSH or after warm-up without SSH. Three-dimensional kinematic and kinetic data and electromyography of biceps femoris long head (BFlh), rectus femoris, and vastus medialis were collected during testing. The maximum length of BFlh during late swing phase increased after SSH with large effect size and close to statistically significant (p = 0.05, d = 1.22), but the knee flexion torque at the peak length did not change significantly. Static stretching of hamstring significantly reduced peak values of both horizontal (d = 1.46) and vertical (d = 1.79) ground reaction forces, and BFlh's activation level during the preactivation (late swing) phase (p = 0.05, d = 2.16). The results indicated that the length of BFlh-knee torque relationship and the length of BFlh-hip torque relationships during the late swing phase and initial stance phase were shifted to the right after SSH, which may reduce risk of hamstring strain injuries. We suggest that preactivity static stretching should not be simply removed and participators should give priority to stretch muscles that are vulnerable to strain injuries.

Acute Effects of Static Stretching of Hamstring on Performance and Anterior Cruciate Ligament Injury Risk During Stop-Jump and Cutting Tasks in Female Athletes.

Ruan, M, Zhang, Q, and Wu, X. Acute effects of static stretching of hamstring on performance and anterior cruciate ligament injury risk during stop-jump and cutting tasks in female athletes. J Strength Cond Res 31(5): 1241-1250, 2017-There is limited research investigating antagonist stretch. The purpose of this study was to evaluate the influence of static stretching of hamstrings (SSH) on performance and anterior cruciate ligament (ACL) injury risk during stop-jump and 180° cutting tasks. Twelve female college athletes (age 20.8 ± 0.7 years; height 1.61 ± 0.05 m; mass 54.25 ± 4.22 kg) participated in this study. Subjects performed stop-jump and 180° cutting tasks under 2 conditions: after warm-up with 4 × 30 seconds SSH or after warm-up without SSH. Three-dimensional kinematic and kinetic data as well as electromyography of biceps femoris, rectus femoris, vastus medialis, and gastrocnemius medialis were collected during testing. Static stretching of hamstrings significantly enhanced jump height by 5.1% (p = 0.009) but did not change the takeoff speed of cutting. No significant changes in peak knee adduction moment or peak anterior tibia shear force were observed with SSH regardless of the task. The peak lateral tibia shear force during cutting was significantly (p = 0.036) reduced with SSH. The co-contraction of hamstring and quadriceps during the preactivation (stop-jump: p = 0.04; cutting: p = 0.05) and downward phases (stop-jump: p = 0.04; cutting: p = 0.05) was significantly reduced after SSH regardless of the task. The results suggest that SSH enhanced the performance of stop-jump because of decreased co-contraction of hamstring and quadriceps but did not change the performance of cutting. In addition, SSH did not increase ACL injury risk during stop-jump and cutting tasks and even reduced medial-lateral knee loading during cutting.

Endothelial cell-anchored tissue factor pathway inhibitor regulates tumor metastasis to the lung in mice.

Tissue factor pathway inhibitor (TFPI) is a physiological inhibitor of the tissue factor (TF)-initiated coagulation pathway. Both circulating and tumor cell-associated TFPI significantly reduce tumor cell-induced coagulation activation and lung metastasis. However, the significance of endothelial cell-anchored TFPI in cancer biology remains largely unexplored. We generated mice with full-length disruption of TFPI (including TFPIα and TFPIß isoforms) in endothelial cells, using a Cre-LoxP system and gene inactivation (GI) strategy. Experimental pulmonary tumor metastasis models were used with TFPI-deficient mice to evaluate the role of endothelial cell-anchored TFPI in cancer progression. Finally, lung microvascular permeability and microenvironment were investigated. TFPI-deficient mice were viable and fertile, and showed decreased plasma TFPI levels and lung TFPI levels as compared with their control littermates. TFPI deficiency in endothelial cells promoted pulmonary tumor metastasis with an increased vascular permeability and altered lung microenvironment. Our observations suggest that endothelial cell-anchored TFPI controls lung tumor metastasis, and does so largely through the inhibition of local TF-induced thrombin generation and the regulation of the lung microenvironment in mice.

Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats.

To investigate age-associated impairments in fluid homeostasis, 4-mo (young) and 32-mo (old) Fischer 344/BN male rats were studied before and after a dietary sodium load. Transferring young rats from a low-sodium (LS) to a high-sodium (HS) diet increased water intake and urine volume by 1.9- and 3.0-fold, respectively, while urine osmolality and plasma aldosterone decreased by 33 and 98%. Concomitantly, adrenocortical angiotensin type 1 receptor (AT1R) density decreased by 35%, and AT1bR mRNA decreased by 39%; no changes were observed in AT1aR mRNA. In contrast, the increase in water intake (1.4-fold) was lower in the old rats, and there was no effect of the HS diet on urine volume or urine osmolality. AT1R densities were 29% less in the old rats before transferring to the HS diet, and AT1R densities were not reduced as rapidly in response to a HS diet compared with the young animals. After 6 days on the HS diet, plasma potassium was lowered by 26% in the old rats, whereas no change was detected in the young rats. Furthermore, while plasma aldosterone was substantially decreased after 2 days on the HS diet in both young and old rats, plasma aldosterone was significantly lower in the old compared with the young animals after 2 wk on the LS diet. These findings suggest that aging attenuates the responsiveness of the adrenocortical AT1R to a sodium load through impaired regulation of AT1bR mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.

OBJECTIVES: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. DESIGN: Experimental animal investigation. SETTING: University research laboratory. SUBJECTS: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. INTERVENTIONS: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. MEASUREMENTS AND MAIN RESULTS: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney injury. CONCLUSION: Our findings demonstrated that xenon preconditioning protected against lipopolysaccharide-induced acute kidney injury via activation of miR-21 target signaling pathways.

Comparison of kinematics and joint moments calculations for lower limbs during gait using markerless and marker-based motion capture.

Objective: This study aimed at quantifying the difference in kinematic and joint moments calculation for lower limbs during gait utilizing a markerless motion system (TsingVA Technology, Beijing, China) in comparison to values estimated using a marker-based motion capture system (Nokov Motion Capture System, Beijing, China). Methods: Sixteen healthy participants were recruited for the study. The kinematic data of the lower limb during walking were acquired simultaneously based on the markerless motion capture system (120 Hz) and the marker-based motion capture system (120 Hz). The ground reaction force was recorded synchronously using a force platform (1,200 Hz). The kinematic and force data were input into Visual3D for inverse dynamics calculations. Results: The difference in the lower limb joint center position between the two systems was the least at the ankle joint in the posterior/anterior direction, with the mean absolute deviation (MAD) of 0.74 cm. The least difference in measuring lower limb angles between the two systems was found in flexion/extension movement, and the greatest difference was found in internal/external rotation movement. The coefficient of multiple correlations (CMC) of the lower limb three joint moments for both systems exceeded or equaled 0.75, except for the ad/abduction of the knee and ankle. All the Root Mean Squared Deviation (RMSD) of the lower limb joint moment are below 18 N·m. Conclusion: The markerless motion capture system and marker-based motion capture system showed a high similarity in kinematics and inverse dynamic calculation for lower limbs during gait in the sagittal plane. However, it should be noted that there is a notable deviation in ad/abduction moments at the knee and ankle.