Risk stratification model integrating nutritional and inflammatory factors for predicting 1-year mortality after valvular heart surgery: a retrospective cohort study.

INTRODUCTION: Existing risk-scoring systems for cardiac surgery include only standard preoperative factors without considering nutritional and inflammatory status or intraoperative factors. The objective of this study was to develop a comprehensive prediction model for mortality incorporating nutritional, inflammatory, and perioperative factors in patients undergoing valvular heart surgery. MATERIALS AND METHODS: In this retrospective review of 2046 patients who underwent valvular heart surgery, Cox and LASSO regression analyses were performed to identify independent prognostic factors for 1-year postoperative mortality among various perioperative factors known to affect prognosis, including objective nutritional and inflammatory indices. A novel nomogram model incorporating selected prognostic factors was developed, and its discrimination ability was evaluated using the C-index. The model was validated in internal and external cohorts. RESULTS: The 1-year mortality rate after valvular heart surgery was 5.1% (105 of 2046 patients) and was significantly associated with several preoperative objective inflammatory and nutritional indices. Cox and LASSO analyses identified the following five independent prognostic factors for mortality: monocyte-to-lymphocyte ratio (an objective inflammatory index), EuroSCORE II, Controlling Nutritional Status score, cardiopulmonary bypass time, and number of erythrocyte units transfused intraoperatively. The nomogram model incorporating these five factors had a C-index of 0.834 (95% CI: 0.791-0.877), which was higher than that of EuroSCORE II alone (0.744, 95% CI: 0.697-0.791) ( P <0.001). The nomogram achieved good discrimination ability, with C-indices of 0.836 (95% CI: 0.790-0.878) and 0.727 (95% CI: 0.651-0.803) in the internal and external validation cohorts, respectively, and showed well-fitted calibration curves. CONCLUSIONS: A nomogram model incorporating five inflammatory, nutritional, and perioperative factors, as well as EuroSCORE II, was a better predictor of 1-year mortality after valvular heart surgery than EuroSCORE II alone, with good discrimination and calibration power for predicting mortality in both internal and external validation cohorts.

Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis.

Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid-blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.

Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study.

PURPOSE: The estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR6m <60 mL/min/1.73 m² (eGFR6m <60) and identify the risk factors that can predict the occurrence of eGFR6m <60 in living kidney donors. MATERIALS AND METHODS: Living kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR6m <60 occurrence were determined using the Youden index. RESULTS: The eGFR6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863-0.908] vs. 0.862 (95% CI, 0.838-0.887), p<0.001}. CONCLUSION: The incidence of eGFR6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR6m <60.

Effects of arginase inhibition on myocardial Ca2+ and contractile responses.

Nitric oxide (NO) is thought to increase cardiac contractility by increasing cytosolic Ca2+ concentration ([Ca2+ ]cyt ) during excitation. Alternatively, NO could increase the sensitivity of the contractile response to [Ca2+ ]cyt (Ca2+ sensitivity). Arginase regulates NO production by competing with NO synthase (NOS), and thus, arginase inhibition should increase cardiac contractility by increasing NO production. We hypothesized that arginase inhibition increases cardiac contractility by increasing both [Ca2+ ]cyt and Ca2+ sensitivity. [Ca2+ ]cyt and contractile (sarcomere length [SL] shortening) responses to electrical stimulation were measured simultaneously in isolated rat cardiomyocytes using an IonOptix system. In the same cardiomyocytes, measurements were obtained at baseline, following 3-min exposure to an arginase inhibitor (S-[2-boronoethyl]-l-cysteine; BEC) and following 3-min exposure to BEC plus a NOS inhibitor (NG -nitro-l-arginine-methyl ester; l-NAME). These responses were compared to time-matched control cardiomyocytes that were untreated. Compared to baseline, BEC increased the amplitude and the total amount of evoked [Ca2+ ]cyt , and the extent and velocity of SL shortening in cardiomyocytes, whereas addition of l-NAME mitigated these effects. The [Ca2+ ]cyt at 50% contraction and relaxation were not different across treatment groups indicating no effect of BEC on Ca2+ sensitivity. The [Ca2+ ]cyt and SL shortening responses in time-matched controls did not vary with time. Arginase inhibition by BEC significantly increased the amplitude and the total amount of evoked [Ca2+ ]cyt , and the extent and velocity of SL shortening in cardiomyocytes, but did not affect Ca2+ sensitivity. These effects of BEC were mitigated by l-NAME. Together, these results indicate an effect of NO on [Ca2+ ]cyt responses that then increase the contractile response of cardiomyocytes.

Uncovering the mesendoderm gene regulatory network through multi-omic data integration.

Mesendodermal specification is one of the earliest events in embryogenesis, where cells first acquire distinct identities. Cell differentiation is a highly regulated process that involves the function of numerous transcription factors (TFs) and signaling molecules, which can be described with gene regulatory networks (GRNs). Cell differentiation GRNs are difficult to build because existing mechanistic methods are low throughput, and high-throughput methods tend to be non-mechanistic. Additionally, integrating highly dimensional data composed of more than two data types is challenging. Here, we use linked self-organizing maps to combine chromatin immunoprecipitation sequencing (ChIP-seq)/ATAC-seq with temporal, spatial, and perturbation RNA sequencing (RNA-seq) data from Xenopus tropicalis mesendoderm development to build a high-resolution genome scale mechanistic GRN. We recover both known and previously unsuspected TF-DNA/TF-TF interactions validated through reporter assays. Our analysis provides insights into transcriptional regulation of early cell fate decisions and provides a general approach to building GRNs using highly dimensional multi-omic datasets.

Impact of preoperative nutritional scores on 1-year postoperative mortality in patients undergoing valvular heart surgery.

OBJECTIVE: Malnutrition is a well-recognized risk factor for poor prognosis and mortality. We investigated whether preoperative malnutrition diagnosed with objective nutritional scores affects 1-year mortality in patients undergoing valvular heart surgery. METHODS: In this retrospective cohort observational study, we evaluated the association among the Controlling Nutritional Status score, Prognostic Nutritional Index, and Geriatric Nutritional Risk Index with 1-year mortality in 1927 patients undergoing valvular heart surgery. We identified factors for mortality using multivariable Cox proportional hazard analysis and investigated the utility of nutritional scores for risk stratification. RESULTS: Malnutrition, as identified by a high Controlling Nutritional Status score and low Prognostic Nutritional Index and Geriatric Nutritional Risk Index, was significantly associated with higher 1-year mortality. Kaplan-Meier survival curve showed that mortality significantly increased as the severity of malnutrition increased (log-rank test, P < .001). The predicted discrimination (C-index) was 0.79 with the Controlling Nutritional Status score, 0.77 with the Prognostic Nutritional Index, and 0.73 with the Geriatric Nutritional Risk Index. Each nutritional index (Controlling Nutritional Status; hazard ratio, 1.31, 95% confidence interval, 1.21-1.42, P < .001), the European System for Cardiac Operative Risk Evaluation II (hazard ratio, 1.07, 95% confidence interval, 1.04-1.09, P < .001), and chronic kidney disease (hazard ratio, 2.26, 95% confidence interval, 1.31-3.90, P = .003) were independent risk factors for mortality. The Controlling Nutritional Status score added to the European System for Cardiac Operative Risk Evaluation II significantly increased the predictive discrimination ability for mortality (C-index 0.82, 95% confidence interval, 0.78-0.87, P = .014) compared with the Controlling Nutritional Status or European System for Cardiac Operative Risk Evaluation II alone. CONCLUSIONS: Preoperative malnutrition as assessed by objective nutritional scores was associated with 1-year mortality after valvular heart surgery. The Controlling Nutritional Status score had the highest predictive ability and, when added to the European System for Cardiac Operative Risk Evaluation II, provided more accurate risk stratification.

Effects of Perioperative Dexmedetomidine on Immunomodulation in Uterine Cancer Surgery: A Randomized, Controlled Trial.

OBJECTIVE: Dexmedetomidine has sympatholytic, anti-inflammatory, and analgesic effects and may exert anti-tumor effect by acting on α2A adrenoreceptor. We investigated whether perioperative dexmedetomidine preserves immune function in patients undergoing uterine cancer surgery. METHODS: One hundred patients were randomly assigned to the control or dexmedetomidine groups (50 patients each). Dexmedetomidine was infused at rates of 0.4 µg/kg/h intraoperatively and 0.15 µg/kg/h during the first 24 h postoperatively. The primary outcome was natural killer (NK) cell activity, which was measured preoperatively and 1, 3, and 5 days postoperatively. The inflammatory response was measured by interleukin-6, interferon-γ, and neutrophil/lymphocyte ratio, and pain scores and opioid consumption were assessed. Cancer recurrence or metastasis and death were evaluated 2 years postoperatively. RESULTS: NK cell activity decreased postoperatively in both groups and changes over time were not different between groups (P=0.496). Interferon-γ increased postoperatively in the dexmedetomidine group, whereas it maintained at the baseline value in the control group. Change in interferon-γ differed significantly between groups (P=0.003). Changes in interleukin-6 and neutrophil-lymphocyte ratio were comparable between groups. Both pain score with activity during the first 1 h and opioid consumption during the first 1-24 h postoperatively were lower in the dexmedetomidine group. Rates of cancer recurrence/metastasis (16.3% vs. 8.7%, P=0.227) and death within 2 years postoperatively (6.7% vs. 2.2%, P=0.318) were not different between groups. CONCLUSIONS: Perioperative dexmedetomidine had no favorable impacts on NK cell activity, inflammatory responses, or prognosis, whereas it increased interferon-γ and reduced early postoperative pain severity and opioid consumption in uterine cancer surgery patients.

Effects of bisphenol A on the proliferation, migration, and tumor growth of colon cancer cells: In vitro and in vivo evaluation with mechanistic insights related to ERK and 5-HT3.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical related to the carcinogenesis of estrogen-responsive organs. Although human exposure to BPA mainly occurs via the oral route, its association with colon cancer has not been fully elucidated. We investigated the effects of BPA on the proliferation, migration, and tumor growth of colon cancer cells. BPA significantly promoted the proliferation of HT-29 human colon adenocarcinoma cells in a time- and dose-dependent manner. BPA also increased HT-29 cells migration. BPA increased the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibition of the ERK pathway attenuated BPA-induced proliferation and migration. In addition, BPA reduced E-cadherin expression, a key factor impeding epithelial-to-mesenchymal transition, and increased 5-HT3 receptors expression, a major mitogenic factor. In xenograft models, tumor volume of the BPA-treated nude mice was 4.6 times that of the saline-treated group. Our findings provide primary evidence regarding the link between BPA and human colon cancer by demonstrating that BPA promotes the proliferation, migration, and tumor growth of colon cancer cells in both in vitro and in vivo models. In addition, we provided the mechanism of action of BPA, involved in the activation of the ERK pathway, the decrease in E-cadherin, and the increase in 5-HT3 receptors.

The Effect of Intraoperative Fluid Management According to Stroke Volume Variation on Postoperative Bowel Function Recovery in Colorectal Cancer Surgery.

Stroke volume variation (SVV) has been used to predict fluid responsiveness; however, it remains unclear whether goal-directed fluid therapy using SVV contributes to bowel function recovery in abdominal surgery. This prospective randomized controlled trial aimed to compare bowel movement recovery in patients undergoing colon resection surgery between groups using traditional or SVV-based methods for intravenous fluid management. We collected data between March 2015 and July 2017. Bowel function recovery was analyzed based on the gas-passing time, sips of water time, and soft diet (SD) time. Finally, we analyzed data from 60 patients. There was no significant between-group difference in the patients' characteristics. Compared with the control group (n = 30), the SVV group (n = 30) had a significantly higher colloid volume and lower crystalloid volume. Moreover, the gas-passing time (77.8 vs. 85.3 h, p = 0.034) and SD time (67.6 vs. 85.1 h, p < 0.001) were significantly faster in the SVV group than in the control group. Compared with the control group, the SVV group showed significantly lower scores of pain on a numeric rating scale and morphine equivalent doses during post-anesthetic care, at 24 postoperative hours, and at 48 postoperative hours. Our findings suggested that, compared with the control group, the SVV group showed a faster postoperative SD time, reduced acute postoperative pain intensity, and lower rescue analgesics. Therefore, SVV-based optimal fluid management is expected to potentially contribute to postoperative bowel function recovery in patients undergoing colon resection surgery.

The immunomodulatory effect of ketamine in colorectal cancer surgery: a randomized-controlled trial.

PURPOSE: Ketamine's inhibitory action on the N-methyl-D-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery. METHODS: A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg-1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg-1·hr-1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery. RESULTS: The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62). CONCLUSIONS: Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients. TRIAL REGISTRATION: www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.

RéSUMé: OBJECTIF: L'action inhibitrice de la kétamine sur le récepteur du N-méthyle-D-aspartate et ses effets anti-inflammatoires pourraient procurer une immunomodulation bénéfique lors d'une chirurgie oncologique. Nous avons étudié l'effet de la kétamine en dose sous-anesthésique en complément à une anesthésie au desflurane sur l'activité des cellules tueuses naturelles (NK) et l'inflammation chez les patients subissant une chirurgie de cancer colorectal. MéTHODE: Au total, 100 patients ont été randomisés à un groupe témoin ou kétamine. Le groupe kétamine a reçu un bolus de 0,25 mg·kg−1 de kétamine cinq minutes avant le début de la chirurgie, suivi d'une perfusion de 0,05 mg·kg−1·h−1 jusqu'à la fin de la chirurgie; le groupe témoin a reçu une quantité similaire de solution physiologique salée. Nous avons mesuré l'activité des cellules NK et des cytokines pro-inflammatoires (interleukine-6 [IL-6] et facteur de nécrose tumorale α [TNF-α]) avant la chirurgie et une, 24 et 48 heures après la chirurgie. La protéine C réactive (CRP) a été mesurée avant la chirurgie puis un, trois et cinq jours après la chirurgie. L'antigène carcinoembryonnaire et la récurrence du cancer ou les métastases ont été évalués deux ans après la chirurgie. RéSULTATS: L'activité des cellules NK a été significativement réduite après la chirurgie dans les deux groupes, mais le changement ne différait pas entre les groupes dans l'analyse de modèle mixte linéaire (P = 0,47). Les changements dans les taux d'IL-6, de TNF-α, de CRP, et d'antigène carcinoembryonnaire n'étaient pas différents entre les groupes (P = 0,27, 0,69, 0,99 et 0,97, respectivement). La récidive du cancer au cours des deux années suivant la chirurgie était similaire entre les groupes (10 % vs 8 %, P = 0,62). CONCLUSION: L'administration peropératoire de kétamine de faible dose ne s'est pas traduite par un quelconque impact favorable sur l'activité postopératoire g des cellules NK, la réaction inflammatoire, et le pronostic chez les patients de chirurgie de cancer colorectal. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03273231); enregistrée le 6 septembre 2017.

Chronic progression of cardiac surgery associated acute kidney injury: Intermediary role of acute kidney disease.

OBJECTIVE: The association between acute kidney injury (AKI) and chronic kidney disease (CKD) remains elusive in cardiac surgery. We investigated the association between postoperative AKI and CKD development, emphasizing the intermediary role of acute kidney disease (AKD), in patients undergoing valvular heart surgery. METHODS: We assessed the occurrence of postoperative AKI (7 days postsurgery), AKD (3 months postsurgery), and CKD (12 months postsurgery) in 1386 patients. The primary outcome was the development of AKD and CKD according to AKI occurrence. Relevant risk factors of AKI, AKD, and CKD were identified through multivariable regression analysis. RESULTS: AKI occurred in 23.9% of patients with normal preoperative renal function. Even with early recovery of renal function within 3 days, AKI increased the risk of AKD (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.98-5.20, P < .001) and CKD (OR, 2.86; 95% CI, 1.68-4.86, P < .001), whereas persistent AKI further increased the risk of AKD (OR, 12.07; 95% CI, 5.56-26.21, P < .001) and CKD (OR, 10.54; 95% CI, 4.01-27.76, P < .001). We also found these relationships in patients with pre-existing renal dysfunction. Multivariable analysis identified 3-month postoperative heart failure and high right ventricular systolic pressure as independent risk factors for CKD. CONCLUSIONS: Even after early recovery, postvalvular heart surgery AKI was associated with increased risk of CKD via AKD in a graded manner related to AKI severity and persistence. Postoperative cardiac dysfunction assessed 3 months postsurgery also significantly influenced CKD development, indicating a need for close follow-up of cardiac and renal function to improve patient outcomes.

Dose-Ranging Study of Ramosetron for the Prevention of Nausea and Vomiting after Laparoscopic Gynecological Surgery: A Prospective Randomized Study.

Patients undergoing laparoscopic gynecologic surgery and receiving postoperative analgesia with opioids have a high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of three doses of ramosetron in this high-risk population. In this prospective, double-blind trial, 174 patients randomly received ramosetron 0.3 mg (R0.3 group; n = 58), 0.45 mg (R0.45 group; n = 58), or 0.6 mg (R0.6 group; n = 58) at the end of surgery. The primary outcome was the incidence of PONV during the first postoperative 48 h. Nausea severity, pain scores, adverse events, and patient satisfaction (1-4; 4, excellent) were assessed. The incidence of PONV was not different between groups (35%, 38%, and 35% in R0.3, R0.45, and R0.6 groups; p = 0.905). Nausea severity, pain scores, and incidence of adverse events (dizziness, headache, or sedation) were similar between groups. Compared to the R0.3 group, the R0.45 and R0.6 groups had lower incidence of premature discontinuation of fentanyl-based patient-controlled analgesia primarily because of intractable PONV (9% and 5% vs. 24%; p = 0.038), and higher satisfaction scores (3.4 ± 0.8 and 3.3 ± 0.7 vs. 2.4 ± 0.9; p = 0.005). Compared to ramosetron 0.3 mg, ramosetron 0.45 and 0.6 mg did not reduce PONV, but reduced premature discontinuation of patient-controlled analgesia and increased patient satisfaction, without increasing adverse events.

DNase-seq to Study Chromatin Accessibility in Early Xenopus tropicalis Embryos.

Transcriptional regulatory elements are typically found in relatively nucleosome-free genomic regions, often referred to as "open chromatin." Deoxyribonuclease I (DNase I) can digest nucleosome-depleted DNA (presumably bound by transcription factors), but DNA in nucleosomes or higher-order chromatin fibers is less accessible to the nuclease. The DNase-seq method uses high-throughput sequencing to permit the interrogation of DNase hypersensitive sites (DHSs) across the entire genome and does not require prior knowledge of histone modifications, transcription factor binding sites, or high quality antibodies to identify potentially active regions of chromatin. Here, discontinuous iodixanol gradients are used as a gentle preparation of the nuclei from Xenopus embryos. Short DNase I digestion times are followed by size selection of digested genomic DNA, yielding DHS fragments. These DNA fragments are subjected to real-time quantitative polymerase chain reaction (qPCR) and sequencing library construction. A library generation method and pipeline for analyzing DNase-seq data are also described.

The Effects of Perioperative Anesthesia and Analgesia on Immune Function in Patients Undergoing Breast Cancer Resection: A Prospective Randomized Study.

Introduction: Perioperative anesthesia and analgesia exacerbate immunosuppression in immunocompromised cancer patients. The natural killer (NK) cell is a critical part of anti-tumor immunity. We compared the effects of two different anesthesia and analgesia methods on the NK cell cytotoxicity (NKCC) in patients undergoing breast cancer surgery. Methods: Fifty patients undergoing breast cancer resection were randomly assigned to receive propofol-remifentanil anesthesia with postoperative ketorolac analgesia (Propofol-ketorolac groups) or sevoflurane-remifentanil anesthesia with postoperative fentanyl analgesia (Sevoflurane-fentanyl group). The primary outcome was NKCC, which was measured before and 24 h after surgery. Post-surgical pain scores and inflammatory responses measured by white blood cell, neutrophil, and lymphocyte counts were assessed. Cancer recurrence or metastasis was evaluated with ultrasound and whole body bone scan every 6 months for 2 years after surgery. Results: The baseline NKCC (%) was comparable between the two groups (P = 0.082). Compared with the baseline value, NKCC (%) increased in the Propofol-ketorolac group [15.2 (3.2) to 20.1 (3.5), P = 0.048], whereas it decreased in the Sevoflurane-fentanyl group [19.5 (2.8) to 16.4 (1.9), P = 0.032]. The change of NKCC over time was significantly different between the groups (P = 0.048). Pain scores during 48 h after surgery and post-surgical inflammatory responses were comparable between the groups. One patient in the Sevoflurane-fentanyl group had recurrence in the contralateral breast and no metastasis was found in either group. Conclusions: Propofol anesthesia with postoperative ketorolac analgesia demonstrated a favorable impact on immune function by preserving NKCC compared with sevoflurane anesthesia and postoperative fentanyl analgesia in patients undergoing breast cancer surgery.

Comparison of the effects of patient-controlled epidural and intravenous analgesia on postoperative bowel function after laparoscopic gastrectomy: a prospective randomized study.

BACKGROUND: Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy. METHOD: Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed. RESULTS: The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h, P = 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively. CONCLUSIONS: Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.

Foxh1 Occupies cis-Regulatory Modules Prior to Dynamic Transcription Factor Interactions Controlling the Mesendoderm Gene Program.

The interplay between transcription factors and chromatin dictates gene regulatory network activity. Germ layer specification is tightly coupled with zygotic gene activation and, in most metazoans, is dependent upon maternal factors. We explore the dynamic genome-wide interactions of Foxh1, a maternal transcription factor that mediates Nodal/TGF-ß signaling, with cis-regulatory modules (CRMs) during mesendodermal specification. Foxh1 marks CRMs during cleavage stages and recruits the co-repressor Tle/Groucho in the early blastula. We highlight a population of CRMs that are continuously occupied by Foxh1 and show that they are marked by H3K4me1, Ep300, and Fox/Sox/Smad motifs, suggesting interplay between these factors in gene regulation. We also propose a molecular "hand-off" between maternal Foxh1 and zygotic Foxa at these CRMs to maintain enhancer activation. Our findings suggest that Foxh1 functions at the top of a hierarchy of interactions by marking developmental genes for activation, beginning with the onset of zygotic gene expression.

Effect of perioperative sodium bicarbonate administration on renal function following cardiac surgery for infective endocarditis: a randomized, placebo-controlled trial.

BACKGROUND: Patients with infective endocarditis (IE) have an elevated risk of renal dysfunction because of extensive systemic inflammation and use of nephrotoxic antibiotics. In this randomized, placebo-controlled trial, we investigated whether perioperative sodium bicarbonate administration could attenuate postoperative renal dysfunction in patients with IE undergoing cardiac surgery. METHODS: Seventy patients randomly received sodium chloride (n = 35) or sodium bicarbonate (n = 35). Sodium bicarbonate was administered as a 0.5 mmol/kg loading dose for 1 h commencing with anesthetic induction, followed by a 0.15 mmol/kg/h infusion for 23 h. The primary outcome was peak serum creatinine (SCr) level during the first 48 h postoperatively. The incidence of acute kidney injury, SCr level, estimated glomerular filtration rate, and major morbidity endpoints were assessed postoperatively. RESULTS: The peak SCr during the first 48 h postoperatively (bicarbonate vs. CONTROL: 1.01 (0.74, 1.37) mg/dl vs. 0.88 (0.76, 1.27) mg/dl, P = 0.474) and the incidence of acute kidney injury (bicarbonate vs. CONTROL: 29% vs. 23%, P = 0.584) were similar in both groups. The postoperative increase in SCr above baseline was greater in the bicarbonate group than in the control group on postoperative day 2 (0.21 (0.07, 0.33) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.028) and postoperative day 5 (0.23 (0.08, 0.36) mg/dl vs. 0.06 (0.00, 0.23) mg/dl, P = 0.017). CONCLUSIONS: Perioperative sodium bicarbonate administration had no favorable impact on postoperative renal function and outcomes in patients with IE undergoing cardiac surgery. Instead, it was associated with possibly harmful renal effects, illustrated by a greater increase in SCr postoperatively, compared to control. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01920126 . Registered on 31 July 2013.