Ropivacaine Administration Suppressed A549 Lung Adenocarcinoma Cell Proliferation and Migration via ACE2 Upregulation and Inhibition of the Wnt1 Pathway.

BACKGROUND: Previous studies have suggested that perioperative anesthesia could have direct impacts on cancer cell biology. The present study investigated the effects of ropivacaine administration on lung adenocarcinoma cells. METHODS: Ropivacaine was administered to A549 cells at concentrations of 0.1, 1, and 6 mM for 2 h. Angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) transfection was performed 6 h prior to ropivacaine administration. Cell proliferation and migration were assessed with cell counting kit 8 (CCK-8) and a wound healing assay at 0 and 24 h after anesthesia exposure. PCR arrays were performed, followed by PCR validation. RESULTS: Ropivacaine administration inhibited A549 cell proliferation and migration in a concentration-dependent manner, with ACE2 upregulation and HIF1α (hypoxia-inducible factor 1α) downregulation. The anticancer effect of ropivacaine was canceled out via ACE2 siRNA transfection. PCR arrays showed specific gene change patterns in the ropivacaine and respective ACE2-knockdown groups. EGFR (epidermal growth factor receptor), BAX (Bcl-2-associated X protein) and BCL2 (B-cell/CLL lymphoma 2) were suppressed with ropivacaine administration; these effects were reversed via ACE2 siRNA induction. CONCLUSION: Ropivacaine administration inhibited A549 cell biology in conjunction with ACE2 upregulation via the inhibition of the Wnt1 (wingless/Integrated 1) pathway.

Canonical and Non-Canonical Functions of Erythropoietin and Its Receptor in Mature Nucleated Erythrocytes of Western Clawed Frog, Xenopus tropicalis.

Enucleated erythrocytes are characteristic of adult mammals. In contrast, fish, amphibians, reptiles, birds, and fetal mammals possess nucleated erythrocytes in their circulation. Erythroid maturation is regulated by erythropoietin (EPO) and its receptor (EPOR), which are conserved among vertebrates. In mammals, EPOR on the erythroid progenitor membrane disappears after terminal differentiation. However, in western clawed frog, Xenopus tropicalis, mature erythrocytes maintain EPOR expression, suggesting that they have non-canonical functions of the EPO-EPOR axis rather than proliferation and differentiation. In this study, we investigated the non-canonical functions of EPOR in Xenopus mature erythrocytes. EPO stimulation of peripheral erythrocytes did not induce proliferation but induced phosphorylation of intracellular proteins, including signal transducer and activator of transcription 5 (STAT5). RNA-Seq analysis of EPO-stimulated peripheral erythrocytes identified 45 differentially expressed genes (DEGs), including cytokine inducible SH2 containing protein gene (cish) and suppressor of cytokine signaling 3 gene (socs3), negative regulators of the EPOR-Janus kinase (JAK)-STAT pathway. These phosphorylation studies and pathway analysis demonstrated the activation of the JAK-STAT pathway through EPO-EPOR signaling in erythrocytes. Through comparison with EPO-responsive genes in mouse erythroid progenitors obtained from a public database, we identified 31 novel EPO-responsive genes indicating non-canonical functions. Among these, we focused on ornithine decarboxylase 1 gene (odc1), which is the rate-limiting enzyme in polyamine synthesis and affects hematopoietic progenitor differentiation and the endothelial cell response to hypoxic stress. An EPO-supplemented culture of erythrocytes showed increased odc1 expression followed by a decrease in polyamine-rich erythrocytes, suggesting EPO-responsive polyamine excretion. These findings will advance our knowledge of the unknown regulatory systems under the EPO-EPOR axis and functional differences between vertebrates' nucleated and enucleated erythrocytes.

Dexmedetomidine Might Exacerbate Acute Kidney Injury, While Midazolam Might Have a Postconditioning Effect: A Rat Model of Lipopolysaccharide-Induced Acute Kidney Injury.

BACKGROUND: The preconditioning effects of dexmedetomidine and propofol on septic acute kidney injury (AKI) have been reported, but the postconditioning effects remain unknown. This study investigated the postconditioning effects of dexmedetomidine, midazolam, and propofol on septic AKI. METHODS: Forty-eight male Wistar rats were intraperitoneally administered lipopolysaccharide (LPS; 8.3 mg kg-1) or normal saline. Twenty-four hours later, rats were allocated to specific anesthetic groups (n=6 each) and exposed for 6 h, as follows: C, control (no anesthetic); D, dexmedetomidine (5 µg kg-1 h-1); M, midazolam (0.6 mg kg-1 h-1); or P, propofol (10 mg kg-1 h-1). Serum creatinine (Cr) and cystatin C (CysC) were measured at the end of anesthesia. Western blot and immunofluorescent analyses of kidney samples were performed. RESULTS: Among LPS-treated groups, D group showed worsened renal dysfunction (L-C vs L-D: Cr, P=0.002, effect size (η2) =0.83; CysC, P=0.004, η2=0.71), whereas M group showed improved renal function (L-C vs L-M: Cr, P=0.009, η2=0.55). In immunofluorescent analysis of renal tubules, D group showed increased expression of nuclear factor κB (NFκΒ) (L-C vs L-D: NFκΒ, P=0.002, η2=0.75; phospho-NFκΒ, P=0.018, η2=0.66) and inhibitor of κ light polypeptide gene enhancer in B-cell kinase ß (IKKß) (L-C vs L-D: IKKß, P=0.002, η2=0.59; phospho-IKKα/ß, P=0.004, η2=0.59), whereas M group showed decreased NFκB expression (L-C vs L-M: NFκB, P=0.003, η2=0.55; phospho-NFκB, P=0.013, η2=0.46). CONCLUSIONS: Dexmedetomidine administration might worsen septic AKI, while midazolam might preserve kidney function via the NFκΒ pathway.

Associations among preoperative transthoracic echocardiography variables and cerebral near-infrared spectroscopy values at baseline before anesthesia in patients undergoing cardiac surgery: a retrospective observational study.

Cerebral tissue oximetry with near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. To date, reduced baseline cerebral NIRS values have been attributed to reduced cerebral blood flow primarily based on a significant positive correlation between left ventricular ejection fraction (LVEF) and baseline rSO2 measured with the INVOS 5100C oximeter. Reportedly, however, rSO2, but not StO2 measured with the FORESIGHT Elite oximeter, correlated with LVEF. We, thus, investigated associations among baseline NIRS values measured with three different oximeters before anesthesia for cardiac surgery and preoperative transthoracic echocardiography (TTE) variables, including LVEF, to examine whether there are inter-device differences in associations among baseline NIRS values and TTE variables. Using Spearman's correlation coefficient, we retrospectively investigated associations among 15 preoperative TTE variables, including LVEF, and baseline NIRS values, including rSO2, StO2, and TOI with the NIRO-200NX oximeter in 1346, 515, and 301 patients, respectively. Only rSO2 (p < 0.00001), but not TOI or StO2 (p > 0.05), positively correlated with LVEF. On the other hand, baseline rSO2, TOI, and StO2 consistently, negatively correlated with the left atrial diameter index (LADI), early diastolic transmitral flow velocity (E), E-to-early diastolic mitral annular velocity ratio (E/e'), estimated right ventricular systolic pressure (eRVP), and inferior vena cava diameter index (IVCDI) (p < 0.0005 to p < 0.00001). Because all of these five TTE variables could be positively associated with right as well as left ventricular filling pressure, our results indicated that reduced baseline NIRS values were consistently associated not with reduced LVEF but with TTE findings indicative of elevated biventricular filling pressure. Our data suggest that regional venous congestion greatly contributes to reduced baseline NIRS values in patients undergoing cardiac surgery.

The neutrophil to lymphocyte ratio and serum albumin as predictors of acute kidney injury after coronary artery bypass grafting.

Postoperative acute kidney injury (AKI) is a highly prevalent and serious complication after cardiac surgery. The aim of this study is to identify the predictors of AKI and the cut-off values after isolated off-pump coronary artery bypass grafting (OPCAB). A total of 329 adult patients, who underwent isolated OPCAB between December 2008 and February 2021, were retrospectively analyzed. The patients were divided into three groups: non-AKI, early AKI and late AKI groups. The early AKI group or the late AKI group were defined as 'having AKI that occurred before or after 48 h postoperatively', respectively. Multivariate logistic regression analysis was performed to identify the predictors of AKI. Receiver operating characteristic (ROC) curve analysis was used to evaluate the cutoff value, the sensitivity, and the specificity of the predictors. On the multivariate analysis, the emergency surgery, the preoperative serum albumin, and the postoperative day 1 neutrophil to lymphocyte ratio (NL ratio) were identified as the independent predictors of AKI. However, neither albumin nor the NL ratio predicted late AKI. The present study showed the preoperative albumin and the postoperative day 1 NL ratio were the robust and independent predictors of postoperative early AKI in isolated OPCAB.

Continuing versus withholding angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) combination tablets during perioperative periods in patients undergoing minor surgery: a single-blinded randomized controlled trial.

PURPOSE: This trial was conducted to compare effects of continuing versus withholding single-pill combination tablets consisting of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on perioperative hemodynamics and clinical outcomes. METHODS: Patients undergoing minor abdominal or urological surgery (n = 106) were randomly assigned to Group C, in which ARB/CCB combination tablets were continued until surgery, or Group W, in which they were withheld within 24 h of surgery. Perioperative hemodynamics and clinical outcomes were compared between the Groups. RESULTS: The incidence of hypotension during anesthesia requiring repeated treatment with vasoconstrictors was higher in Group C than Group W (p = 0.0052). Blood pressure during anesthesia was generally lower in Group C than Group W (p < 0.05) despite significantly more doses of ephedrine and phenylephrine administrated in Group C (p = 0.0246 and p = 0.0327, respectively). The incidence of postoperative hypertension did not differ between Groups (p = 0.3793). Estimated glomerular filtration rate (eGFR) on the preoperative day did not differ between Groups (p = 0.7045), while eGFR was slightly lower in Group C than Group W on the first and third postoperative days (p = 0.0400 and p = 0.0088, respectively), although clinically relevant acute kidney injury did not develop. CONCLUSIONS: Continuing ARB/CCB combination tablets preoperatively in patients undergoing minor surgery increased the incidence of hypotension during anesthesia, increased requirements of vasoconstrictors to treat hypotension, and might deteriorate postoperative renal function, albeit slightly. These results suggest that withholding ARB/CCB tablets preoperatively is preferable to continuing them. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials (jRCT) at Japanese Ministry of Health, Labour, and Welfare (Trial ID: jRCT1031190027).

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Clinical and radiological findings of silent hypoxia among COVID-19 patients.

The aim of this study was to describe the clinical and radiological findings of COVID-19 patients with "silent hypoxia," who had no dyspnea on admission even though their oximetry saturation was less than 94%. This retrospective cohort study included all COVID-19 patients (n = 270) at a large tertiary care hospital between January 31 and August 31, 2020. Clinical and radiological characteristics of patients who met our criteria of "silent hypoxia", which included those who reported no dyspnea even though oximetry saturation was <94%, were extracted. Eight patients (3.0%) met the criteria for "silent hypoxia." The median age was 61 years (interquartile range [IQR]: 48.8-72.3), and five (62.5%) were men. All patients had consolidation on CT and showed a moderate to high COVID-19 CT severity score (median: 13.5, IQR: 10.8-15.3). The median FIO2 of the maximum oxygen required was 55 (IQR: 28-70)%. Two patients (25.0%) were intubated, and one patient (12.5%) underwent extracorporeal membrane oxygenation. Some COVID-19 patients with "silent hypoxia" may develop severe disease. Close and accurate monitoring of patients using arterial blood gas and pulse oximetry is necessary, regardless of their symptoms.

Cerebral oxygen saturation (rSO2) during cardiopulmonary bypass (CPB) measured using the INVOS oximeter closely correlates with baseline rSO2.

Baseline cerebral regional saturation (rSO2) measured using the INVOS 5100C (Medtronic, MN, USA) varies widely among patients with cardiac and/or renal diseases. To identify significant correlates of baseline rSO2 and to investigate intraoperative rSO2 changes, we conducted a retrospective study in 494 patients undergoing on-pump cardiovascular surgery. Correlations between preoperative blood laboratory test variables and baseline rSO2 before anesthesia were examined. Intraoperative rSO2 changes were analyzed. Of all the variables examined, log-transformed B-type natriuretic peptide (BNP) most significantly and negatively correlated with baseline rSO2 (r = - 0.652, p < 0.0001). Intraoperatively, rSO2 showed the lowest value during cardiopulmonary bypass (CPB) (median rSO2: 56.2% during CPB vs. 63.9% at baseline, p < 0.0001). Although rSO2 during CPB correlated positively with hemoglobin concentration and oxygen delivery during CPB (r = 0.192, p < 0.0001; and r = 0.172, p = 0.0001, respectively), it correlated much more closely with baseline rSO2 (r = - 0.589, p < 0.0001). Thus, patients showing low baseline rSO2 primarily associated with preoperatively high BNP continued to show low rSO2 even during CPB independent of hemodynamics artificially controlled by CPB. Our findings suggest that low baseline rSO2 in patients with high BNP due to cardiac and/or renal diseases is more likely to result from tissue edema causing alterations in optical pathlength and thus in calculated rSO2 values, not readily modifiable with CPB, rather than actual cerebral hemodynamic alterations readily modifiable with CPB. These may partly explain why the INVOS oximeter is a trend monitor requiring baseline measures.

Interim 2019/2020 Influenza Vaccine Effectiveness in Japan from October 2019 to January 2020.

Herein, we report the interim vaccine effectiveness (VE) of a quadrivalent inactivated influenza vaccine, during the 2019/2020 influenza season, in Japan. We conducted a retrospective observational cohort study of 381 patients aged ≥15 years, who were enrolled with influenza like illnesses and examined via the rapid influenza diagnostic test, at the Ambulatory Care unit of the National Center for Global Health and Medicine in Tokyo, Japan, from the beginning of October 2019 to the end of January 2020. VE was estimated using a test-negative design. VE was calculated as (1 - odds ratio) × 100%, comparing influenza A test positivity between vaccinated and unvaccinated patients. Of the 381 patients initially screened for inclusion, 314 were enrolled in the study. Of these, 105 were vaccinated, 98 were diagnosed with influenza A, and 5 were diagnosed with influenza B. Overall VE against influenza A was 27.6% (95% confidence interval [CI], ‒21.1 to +57.4), and in patients aged ≥65 years, it was 47.3% (95% CI, ‒76.0 to +86.0). This indicates that the influenza vaccination offered continued protection during the 2019/2020 influenza season, but a detailed analysis of more cases with a careful consideration of methodology is necessary to estimate VE more precisely.

Factors Associated with Postoperative Nausea and Vomiting after Breast Cancer Surgery with Inhalation Anesthesia.

BACKGROUND: The incidence and risk factors of postoperative nausea and vomiting (PONV) and early PONV (ePONV) were evaluated in patients who underwent breast surgery with volatile anesthesia. METHODS: In this retrospective study, multivariate logistic regression was used to determine incidence and identify risk factors for PONV. RESULTS: Among 928 patients, 166 (18%) and 220 (24%) had ePONV and PONV, respectively. In multivariate analysis, anesthesia duration and use of desflurane were independent risk factors for ePONV. For PONV, anesthesia duration and Apfel score were independent risk factors. CONCLUSIONS: Our results indicate that desflurane was the main cause of ePONV. However, during the delayed phase, a higher Apfel score was the strongest predictor. In the early and delayed phases, long anesthesia duration was associated with high risk of PONV. Thus, prolonged anesthesia and desflurane use should be avoided for patients at high risk of PONV, particularly those with high Apfel scores.

Impact of frailty on protocol-based weaning from mechanical ventilation in patients with sepsis: a retrospective cohort study.

AIM: Frailty has been shown to be associated with prolonged mechanical ventilation (MV). However, due to limited physiological data, it has been unclear how frailty affects weaning from MV in septic patients subjected to a specific weaning protocol. METHODS: This was a single-center retrospective cohort study. The study included patients with sepsis on MV who underwent protocol-based weaning between August 2015 and December 2018. Frailty was defined as a Clinical Frailty Scale score 4 or more. The association between frailty and weaning was evaluated. RESULTS: Ninety-nine eligible patients were identified and categorized as frail (n = 67) or not frail (n = 32). The duration of MV was significantly longer in the frail group (8 days versus 5 days, P < 0.01). In multivariate analysis, frailty was independently associated with duration of MV (regression coefficient 17.97, 95% confidence interval 1.77-34.17) and successful weaning (hazard ratio 0.60, 95% confidence interval 0.36-1.00). There was no significant between-group difference in duration until the first separation attempt or reintubation rate. Respiratory failure was significantly more common in the frail group as a cause of weaning failure, whereas airway failure was common in both groups. CONCLUSION: Frailty was independently associated with a longer duration of MV in patients with sepsis who underwent protocol-based weaning. Frail patients were more likely to fail spontaneous breathing trials than nonfrail patients during the weaning process, although the risk after extubation was similar.

Opioid-free anesthesia for a child with trisomy 13 with obstructive sleep apnea: a case report.

BACKGROUND: Most children with trisomy 13 display central apnea, and are prone to opioid-induced respiratory depression. We conducted opioid-free anesthesia for a patient with trisomy 13 and obstructive sleep apnea, and safely extubated the patient in the operating room. CASE PRESENTATION: A 27-month-old girl with trisomy 13 underwent tonsillectomy. Given her high sensitivity to opioids, general anesthesia was introduced and maintained only with 2-5% sevoflurane and 33% nitrous oxide in oxygen. We used acetaminophen for postoperative analgesia. The tracheal tube was removed under stable breathing pattern 10 min after the surgery in the operating room. Two years later, opioid-free anesthesia with 2-5% sevoflurane and 33% nitrous oxide in oxygen was again performed safely for tube insertion into both eardrums. CONCLUSION: Opioid-free anesthesia with adequate non-narcotic analgesics is safe for children with trisomy 13 with multiple apnea-related comorbidities.

Specific microRNAs are involved in the reno­protective effects of sevoflurane preconditioning and ischemic preconditioning against ischemia reperfusion injury in rats.

The kidneys are prone to developing ischemia reperfusion injury (IRI) following certain renal surgeries and cardiovascular surgeries requiring cardiac arrest. Sevoflurane and ischemic preconditioning reportedly alleviate IRI, which is mediated via microRNAs. The present study compared anesthetic preconditioning (APC) and ischemic preconditioning (IPC) on microRNAs, which promote cell­survival pathways in rats in a randomized controlled study. After undergoing right nephrectomy under general anesthesia, male Wistar rats (336±24 g) and were divided into four groups (IRI, APC, IPC and sham; n=7 each). The IRI group underwent 45 min clamping of the left renal vasculature, followed by 4 h of reperfusion. APC involved exposure to one minimum alveolar concentration sevoflurane for 15 min. IPC included three cycles of two­min clamping and five­min reperfusion. Blood and renal biopsy samples were assessed postoperatively to measure serum creatinine and to analyze renal microRNA (miR) expression using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) testing and their target pathways with Ingenuity Pathway Analysis™. The present study found that serum creatinine values in APC (0.71±0.08 mg/dl) and IPC (0.73±0.1 mg/dl) groups were lower than in the IRI group (0.96±0.13 mg/dl; P<0.05), indicating amelioration of IRI by APC and IPC. RT­qPCR followed by pathway analysis indicated that APC and IPC affect 'protein kinase B (Akt)'. APC promoted miR­17­3p and suppressed miR­27a. IPC promoted miR­19a. All the miRs were predicted to regulate phosphorylated Akt, which promotes cell­protection. Western blot analysis showed that expression of phosphorylated Akt increased and phosphatase and tensin homologue deleted from chromosome 10 (PTEN) decreased following APC and IPC. The present study concluded that APC and IPC affect different miRs, although they are estimated to similarly promote the PTEN/phosphoinositide 3­kinase/Akt signaling pathway, resulting in reno­protection.

Study protocol for single-center, open-label, randomized controlled trial to clarify the preventive efficacy of electrical stimulation for muscle atrophy after trauma.

BACKGROUND: Management of trauma involves long-term bed rest even when muscle strength in the lower extremities is preserved. Prolonged bed rest reduces muscle mass and causes muscle atrophy. A recent study reported the efficacy of rehabilitation using electrical muscle stimulation (EMS) for muscle strength maintenance in intensive care unit patients with disturbance of consciousness. However, despite the expected benefits of EMS in maintaining muscle strength, little is known about its efficacy in trauma patients. METHODS/DESIGN: A single-center, open-label, randomized controlled trial of 40 patients with pelvic fracture to test the effectiveness of 14 days of EMS. The primary outcome will be change in cross-sectional area of the thigh muscle between pre and post intervention, as measured on computed tomography images. We will analyze the primary endpoint by analysis of covariance (ANCOVA) and analyze the secondary endpoints in an exploratory manner. CONCLUSION: If our hypothesis is confirmed, this study will provide evidence that the use of EMS can be effective in preventing muscle atrophy. TRIAL REGISTRATION: UMIN registration number: UMIN000030190 . Registered on 1 December 2017.

B-Type Natriuretic Peptide and Hemoglobin are Two Major Factors Significantly Associated With Baseline Cerebral Oxygen Saturation Measured Using the INVOS Oximeter in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery.

OBJECTIVES: To investigate an association between the preoperative plasma B-type natriuretic peptide (BNP) concentration and cerebral regional saturation (rSO2) measured using the INVOS oximeter (Medtronic, Minneapolis, MN). DESIGN: A retrospective data analysis. SETTING: Single university hospital. PARTICIPANTS: Patients undergoing off-pump coronary artery bypass (OPCAB) surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Associations of variables obtained from preoperative blood laboratory tests and transthoracic echocardiography with baseline rSO2 before induction of general anesthesia were investigated using bivariate and multivariate regression analyses in 330 OPCAB patients. With bivariate analyses, age; body size-related variables such as weight and body surface area; hematologic function-related variables such as blood hemoglobin (Hb) concentration and arterial oxygen saturation; renal function-related variables including estimated glomerular filtration rate, creatinine, and blood urea nitrogen; hepatic function-related variables including cholinesterase, albumin, total bilirubin, and alanine aminotransferase; serum electrolytes including sodium, chloride, and phosphorus; BNP or log-transformed BNP; and 13 transthoracic echocardiography variables such as left ventricular ejection fraction highly significantly correlated with baseline rSO2 (p < 0.0001). However, the multiple regression analysis revealed that only BNP and Hb remained major factors significantly associated with baseline rSO2 (p < 0.0001), while estimated glomerular filtration rate, arterial oxygen saturation, and body surface area remained minor factors (p < 0.05). Baseline rSO2 correlated better with log-transformed BNP than with BNP, indicating that rSO2 correlated with BNP in an exponential fashion. CONCLUSIONS: Preoperative BNP and Hb concentrations were 2 major factors associated with INVOS rSO2 in patients undergoing OPCAB.

Brain natriuretic peptide (BNP) may play a major role in risk stratification based on cerebral oxygen saturation by near-infrared spectroscopy in patients undergoing major cardiovascular surgery.

PURPOSE: A previous study reported that low baseline cerebral oxygen saturation (ScO2) (≤50%) measured with near-infrared spectroscopy was predictive of poor clinical outcomes after cardiac surgery. However, such findings have not been reconfirmed by others. We conducted the current study to evaluate whether the previous findings would be reproducible, and to explore mechanisms underlying the ScO2-based outcome prediction. METHODS: We retrospectively investigated 573 consecutive patients, aged 20 to 91 (mean ± standard deviation, 67.1 ± 12.8) years, who underwent major cardiovascular surgery. Preanesthetic baseline ScO2, lowest intraoperative ScO2, various clinical variables, and hospital mortality were examined. RESULTS: Bivariate regression analyses revealed that baseline ScO2 correlated significantly with plasma brain natriuretic peptide concentration (BNP), hemoglobin concentration (Hgb), estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) (p < 0.0001 for each). Baseline ScO2 correlated with BNP in an exponential manner, and BNP was the most significant factor influencing ScO2. Logistic regression analyses revealed that baseline and lowest intraoperative ScO2 values, but not relative ScO2 decrements, were significantly associated with hospital mortality (p < 0.05), independent of the EuroSCORE (p < 0.01). Receiver operating curve analysis of ScO2 values and hospital mortality revealed an area under the curve (AUC) of 0.715 (p < 0.01) and a cutoff value of ≤50.5% for the baseline and ScO2, and an AUC of 0.718 (p < 0.05) and a cutoff value of ≤35% for the lowest intraoperative ScO2. Low baseline ScO2 (≤50%) was associated with increases in intubation time, intensive care unit stay, hospital stay, and hospital mortality. CONCLUSION: Baseline ScO2 was reflective of severity of systemic comorbidities and was predictive of clinical outcomes after major cardiovascular surgery. ScO2 correlated most significantly with BNP in an exponential manner, suggesting that BNP plays a major role in the ScO2-based outcome prediction.

High-dose remifentanil suppresses stress response associated with pneumoperitoneum during laparoscopic colectomy.

PURPOSE: Although laparoscopic surgery is minimally invasive, it produces stress responses to an extent similar to that of conventional laparotomy. Both epidural anesthesia and remifentanil intravenously (i.v.), combined with general anesthesia, provide stable hemodynamics during laparoscopic surgery. However, it has not been elucidated whether epidural anesthesia and remifentanil are associated with suppression of autonomic and neuroendocrine stress responses. This study aimed to clarify whether thoracic epidural anesthesia (TEA) or remifentanil suppresses stress responses during laparoscopic surgery. METHODS: We assigned 60 patients undergoing laparoscopic colectomy to three groups anesthetized with 40 % oxygen-air-sevoflurane plus either TEA (TEA group), continuous infusion of remifentanil 0.25 µg/kg/min [low-dose (LD) group], or 1.0 µg/kg/min [high-dose (HD) group] (n = 20 each group). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, antidiuretic hormone (ADH), and catecholamines were measured immediately before anesthesia induction, and 30 and 90 min after the start of pneumoperitoneum. RESULTS: All groups showed no significant changes in hemodynamics during the course of anesthesia. Compared with TEA, both high-dose and low-dose remifentanil significantly suppressed increases in ACTH, ADH, and cortisol during pneumoperitoneum. Plasma adrenaline showed no significant changes during pneumoperitoneum in any group. Compared with TEA, low-dose remifentanil produced significantly higher plasma concentrations of noradrenaline and dopamine during pneumoperitoneum. CONCLUSION: Notwithstanding similar hemodynamic responses in all groups, only high-dose remifentanil suppressed both sympathetic responses and the hypothalamus-pituitary-adrenal axis. This result indicates that of these three anesthesia regimens, high-dose remifentanil seems most suited for laparoscopic surgery.

Effects of lysophosphatidic acid on the in vitro proliferation and differentiation of a novel porcine preadipocyte cell line.

We examined the effects of lysophosphatidic acid (LPA) on in vitro proliferation and differentiation of a porcine preadipocyte cell line, DFAT-P, and a mouse preadipocyte cell line, 3T3-L1. During the proliferation and differentiation phases, DFAT-P and 3T3-L1 cells expressed only the endothelial differentiation gene (EDG)-2 receptor and not EDG-4 and EDG-7 receptors. LPA promoted the proliferation of DFAT-P cells more extensively than that of 3T3-L1 cells. After adipogenic induction, LPA inhibited glycerol-3-phosphate dehydrogenase activity and lipid droplet accumulation, and suppressed peroxisome proliferator-activated receptor γ (PPARγ) protein expression, this inhibitory effect in DFAT-P cells was twice as high as that in 3T3-L1 cells. Furthermore, treatments with low LPA concentrations significantly inhibited adipocyte differentiation in DFAT-P cells but not in 3T3-L1 cells. We conclude that LPA promotes the proliferation of porcine preadipocytes through the EDG-2 receptor but inhibits their differentiation, and these effects depend on the down-regulation of PPARγ expression via the EDG-2 receptor. Furthermore, DFAT-P cells are more sensitive to LPA than 3T3-L1 cells. These findings in a porcine model will contribute to the understanding of LPA action mechanisms on in vitro proliferation and differentiation of preadipocytes in domestic animals and/or humans.