Possible role of QRS duration in the right ventricle as a perioperative monitoring parameter for right ventricular function: a prospective cohort analysis in robotic mitral valve surgery.

Background: The clinical importance of the right ventricle (RV) has recently been recognized; however, assessing its function during cardiac surgery remains challenging owing to its complex anatomy. A temporary transvenous pacing catheter is a useful tool in the small surgical field of minimally invasive cardiac surgery, and an electrocardiogram recorded through the catheter is composed of the direct electrophysiological activity of the RV. Therefore, we hypothesized that QRS duration in the RV (QRSRV) could be a useful monitoring parameter for perioperative RV function. Methods: We conducted a prospective cohort analysis involving adult patients undergoing robotic mitral valve repair. A bipolar pacing catheter was inserted using x-ray fluoroscopy, and the QRSRV duration was assessed at four time points: preoperative baseline, during one-lung ventilation, after weaning from cardiopulmonary bypass, and before the end of surgery. At the same time points, right ventricular fractional area change (RVFAC) measured by transesophageal echocardiography and QRS duration at V5 lead of the body surface electrocardiogram (QRSV5) were also evaluated. Results: In the 94 patients analyzed, QRSRV duration was significantly prolonged during robotic mitral valve repair (p = 0.0009), whereas no significant intraoperative changes in RVFAC were observed (p = 0.2). By contrast, QRSV5 duration was significantly shortened during surgery (p < 0.00001). Multilinear regression showed a significant correlation of QRSRV duration with RVFAC (p = 0.00006), but not with central venous pressure (p = 0.9), or left ventricular ejection fraction (p = 0.3). When patients were divided into two groups by postoperative QRSRV > 100 or ≤100 ms, 25 patients (26.6%) exhibited the prolonged QRSRV duration, and the mean increase in the postoperative QRSRV from preoperative baseline was 12 ms (p = 0.001), which was only 0.6 ms in patients with QRSRV ≤ 100 ms (p = 0.6). Cox regression analysis showed that prolonged postoperative QRSRV duration was the only significant parameter associated with a longer ICU stay after surgery (p = 0.02; hazard ratio, 0.55). Conclusion: Our data suggest that QRSRV duration is a useful parameter for monitoring the RV during cardiac surgery, possibly better than a commonly used echocardiographic parameter, RVFAC. An electrophysiological assessment by QRSRV duration could be a practical tool for the complex anatomy of the RV, especially with limited modalities in perioperative settings.

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition. However, the microenvironmental factors that regulate the iron dependency of ANKL cells remain unclear. In this study, we first revealed that the anti-neoplastic effect of PPMX-T003 was characterized by DNA double-strand breaks in a DNA replication-dependent manner, similar to conventional cytotoxic agents. We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut.

Thoracic epidural analgesia prolongs postoperative QT interval on electrocardiogram in major non-cardiac surgery: a randomized comparison and a prospective cohort analysis.

Introduction: Prolongation of QT interval on electrocardiogram can be associated with perioperative lethal arrhythmia. Epidural analgesia is a commonly used modality to relieve surgical pain by blocking sensory nerves, which also blocks the autonomic nervous system and can affect QT interval. Since patient monitoring becomes much less frequent after surgery than intraoperative period, we investigated the effects of epidural analgesia on postoperative QT interval with a randomized clinical trial and a prospective cohort study. Methods: In a randomized study, we assigned 60 patients undergoing thoracic epidural analgesia to an epidural analgesia or no-epidural analgesia group, in which 3 ml/h of 0.25% epidural levobupivacaine (7.5 mg/h) was administered only in the epidural analgesia group during surgery. The primary outcome was the postoperative heart rate-corrected QT interval. In a prospective cohort study, patients were assigned to receive 5 ml/h epidural levobupivacaine (12.5 mg/h). The plasma concentration of levobupivacaine was measured using liquid chromatography-mass spectrometry. Results: The median postoperative corrected QT interval interval with 3 ml/h epidural levobupivacaine was significantly longer than that without epidural analgesia. Using multiple regression analysis for the factors known to affect postoperative corrected QT interval interval, epidural analgesia was found to be an independent variable for prolongation, and the mean difference of the corrected QT interval interval with or without epidural analgesia was 23 ms after adjustment. The median plasma concentration of levobupivacaine at the end of surgery was 164 ng/ml with 3 ml/h epidural levobupivacaine, and the correlation coefficient to the postoperative corrected QT interval interval was 0.14, showing a not significant correlation. A prospective cohort study showed that 5 ml/h epidural levobupivacaine significantly prolonged postoperative corrected QT interval interval compared to preoperative baseline. The median plasma concentration of levobupivacaine was 166 ng/ml with 5 ml/h, the correlation coefficient of which showed no significant correlation. Conclusion: Thoracic epidural analgesia could enhance postoperative corrected QT interval prolongation after general anesthesia. The mechanism is possibly caused by blocking neighboring or part of the cardiac sympathetic nerves, rather than by systemic effects of epidurally administered levobupivacaine. Clinical trial number: UMIN000013347 for the randomized study and UMIN000041518 for the prospective cohort study, which were registered at University hospital Medical Information Network Center.

The hepatic niche leads to aggressive natural killer cell leukemia proliferation through the transferrin-transferrin receptor 1 axis.

Aggressive natural killer cell leukemia (ANKL) is a rare lymphoid neoplasm frequently associated with Epstein-Barr virus, with a disastrously poor prognosis. Owing to the lack of samples from patients with ANKL and relevant murine models, comprehensive investigation of its pathogenesis including the tumor microenvironment (TME) has been hindered. Here we established 3 xenograft mice derived from patients with ANKL (PDXs), which enabled extensive analysis of tumor cells and their TME. ANKL cells primarily engrafted and proliferated in the hepatic sinusoid. Hepatic ANKL cells were characterized by an enriched Myc-pathway and proliferated faster than those in other organs. Interactome analyses and in vivo CRISPR-Cas9 analyses revealed transferrin (Tf)-transferrin receptor 1 (TfR1) axis as a potential molecular interaction between the liver and ANKL. ANKL cells were rather vulnerable to iron deprivation. PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a noncanonical hematopoietic organ in adults, serves as a principal niche for ANKL and the inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.

Phase 1 Clinical Trial of PPMX-T003, a Novel Human Monoclonal Antibody Specific for Transferrin Receptor 1, to Evaluate Its Safety, Pharmacokinetics, and Pharmacodynamics.

This study aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of PPMX-T003, a novel human monoclonal antibody for transferrin receptor 1 (TFR1), in healthy individuals. Forty participants were enrolled and randomized to PPMX-T003 dose groups (n = 6/group) and the placebo group (n = 10). The safety and pharmacokinetics profiles were assessed according to the sequential, ascending single-dose intravenous infusions of PPMX-T003 from 0.008 mg/kg to 0.25 mg/kg. Adverse events (AEs) after PPMX-T003 administration occurred in 16 of 30 participants. Any severe AE and AE incidence were not reported, but they tended to increase depending on the dose. Laboratory tests, vital signs, and standard 12-lead electrocardiogram showed no clinically relevant changes. Five participants experienced an infusion-related reaction but recovered on days 5-10. Regarding pharmacokinetics, PPMX-T003 has a nonlinear elimination pattern. PPMX-T003 in the 0.25 mg/kg group showed apparent (>50%) decreased serum levels of reticulocytes from day 3 and sustained moderate (<10%) fall of hematocrit and hemoglobin counts from day 7. In conclusion, the antibody-mediated blockade of TFR1 elicited the expected fall in blood cell levels and showed an acceptable safety profile, supporting the continuing development of PPMX-T003 as a new candidate for polycythemia vera treatment.

Symptomatic absorption of normal saline during transurethral resection of the prostate: a case report.

BACKGROUND: Transurethral resection of the prostate (TUR-P) could incidentally cause hyponatremia, known as TUR syndrome due to intravascular absorption of non-electrolytic irrigation fluid. Recently, normal saline has been used as an irrigation fluid in a new system named TURis (TUR in saline) to prevent TUR syndrome. However, rapid massive absorption of normal saline can also cause other systemic adverse events. CASE PRESENTATION: A 71-year-old man underwent TURis for benign prostatic hyperplasia under spinal anesthesia. The patient lost consciousness which led upper airway obstruction and hypoxia 30 min after the surgery began. Blood gas test indicated hyperchloremic metabolic acidosis. While vasoactive agents were ineffective, the administration of bicarbonate significantly improved the symptoms and restored blood pressure. CONCLUSION: We experienced a case of hyperchloremic metabolic acidosis with decreased level of consciousness and hypotension during TURis. Administration of bicarbonate, but not phenylephrine, was effective for recovering blood pressure.

A comparison of HER2/neu accumulations of Ga-67-labeled anti-HER2 antibody with chemically and site-specifically conjugated bifunctional chelators.

Monoclonal antibodies (mAb) developed to target specific cancers have achieved considerable success to date. To further enhance therapeutic efficacy, monoclonal antibodies may be conjugated with a cytotoxic drug or radioisotope. We present the development of a new method based on site-specific conjugation (SSC) for targeting HER2. The study design involves a comparison of the accumulation of Ga-67-labeled anti-HER2 antibodies with SSC (SSC-mAb) versus conventional chemical conjugation (Chem-mAb) in HER2-positive tumors. In vitro, the HER2-binding capacity of SSC-mAb and Chem-mAb was comparable. However, in vitro, the rate of tumor accumulation increased gradually with SSC-mAb not only in the tumors but also in the blood and other organs. The SSC may improve targeted antigen-specific cancer radioimmunotherapy and may, due to higher retention, reduce the amount of treatment required.

Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/leukemia (ATLL) is an aggressive peripheral T-cell malignancy, caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). We have recently shown that cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is specifically and consistently overexpressed in ATLL cells, and functions as a novel cell surface marker. In this study, we first show that a soluble form of CADM1 (sCADM1) is secreted from ATLL cells by mainly alternative splicing. After developing the Alpha linked immunosorbent assay (AlphaLISA) for sCADM1, we showed that plasma sCADM1 concentrations gradually increased during disease progression from indolent to aggressive ATLL. Although other known biomarkers of tumor burden such as soluble interleukin-2 receptor α (sIL-2Rα) also increased with sCADM1 during ATLL progression, multivariate statistical analysis of biomarkers revealed that only plasma sCADM1 was selected as a specific biomarker for aggressive ATLL, suggesting that plasma sCADM1 may be a potential risk factor for aggressive ATLL. In addition, plasma sCADM1 is a useful marker for monitoring response to chemotherapy as well as for predicting relapse of ATLL. Furthermore, the change in sCADM1 concentration between indolent and aggressive type ATLL was more prominent than the change in the percentage of CD4+CADM1+ ATLL cells. As plasma sCADM1 values fell within normal ranges in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with higher levels of serum sIL-2Rα, a measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP.

Phase I Study of P-cadherin-targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors.

PURPOSE: 90Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors. PATIENTS AND METHODS: The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5-25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months. RESULTS: 111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity. CONCLUSIONS: The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.

Development of anti-human CADM1 monoclonal antibodies as a potential therapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a highly invasive and refractory T-cell malignancy, with poor prognosis. We previously identified that cell adhesion molecule 1 (CADM1) is overexpressed consistently in ATLL cells, and that CADM1 expression increases the adhesion capacity of ATLL cells to endothelial cells and promotes the organ invasion of ATLL cells in a xenograft mouse model. In this study, we first show that newly developed several anti-human CADM1 antibodies, which were complete human IgG antibodies generated by phage display method, specifically recognize CADM1 on ATLL cells. Although most of the CADM1 antibodies did not have a direct cytotoxic effect against CADM1-positive ATLL cells, clone 089-084 exhibited weak but significant antibody-dependent cell-mediated cytotoxic activity. Moreover, clone 103-189 effectively inhibits the interaction between endothelial cells and CADM1-positive ATLL cells. Furthermore, in mice bearing intra-splenic transplantation of EL4 mouse lymphoma cells expressing CADM1, the treatment of 103-189 significantly suppressed the organ invasion of CADM1-positive EL4 cells, resulting in improved survival time of mice. Therefore, since the anti-CADM1 antibody may be useful for the suppression of organ invasion in ATLL patients, combination use of the anti-CADM1 antibody with chemotherapy drugs could be beneficial for the efficient elimination of ATLL cells.

Comparison of the venous-arterial CO2 to arterial-venous O2 content difference ratio with the venous-arterial CO2 gradient for the predictability of adverse outcomes after cardiac surgery.

This study aimed to compare the prognostic performance of the ratio of mixed and central venous-arterial CO2 tension difference to arterial-venous O2 content difference (Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2, respectively) with that of the mixed and central venous-to-arterial carbon dioxide gradient (Pv-aCO2 and Pcv-aCO2, respectively) for adverse events after cardiac surgery. One hundred and ten patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled. After catheter insertion, three blood samples were withdrawn simultaneously through arterial pressure, central venous, and pulmonary artery catheters, before and at the end of the operation, and preoperative and postoperative values were determined. The primary end-point was set as the incidence of postoperative major organ morbidity and mortality (MOMM). Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed to evaluate the prognostic reliability of Pv-aCO2, Pcv-aCO2, Pv-aCO2/Ca-vO2, and Pcv-aCO2/Ca-cvO2 for MOMM. MOMM events occurred in 25 patients (22.7%). ROC curve analysis revealed that both postoperative Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2 were significant predictors of MOMM. However, postoperative Pv-aCO2 was the best predictor of MOMM (area under the curve [AUC]: 0.804; 95% confidence interval [CI] 0.688-0.921), at a 5.1-mmHg cut-off, sensitivity was 76.0%, and specificity was 74.1%. Multivariate analysis revealed that postoperative Pv-aCO2 was an independent predictor of MOMM (odds ratio [OR]: 1.42, 95% CI 1.01-2.00, p = 0.046) and prolonged ICU stay (OR: 1.45, 95% CI 1.05-2.01, p = 0.024). Pv-aCO2 at the end of cardiac surgery was a better predictor of postoperative complications than Pv-aCO2/Ca-vO2 and Pcv-aCO2/Ca-cvO2.

Comparison between hemodynamic effects of propofol and thiopental during general anesthesia induction with remifentanil infusion: a double-blind, age-stratified, randomized study.

PURPOSE: Propofol is commonly used with remifentanil for induction of general anesthesia (GA); however, it often leads to hypotension. Intraoperative hypotension is associated with postoperative adverse events. By contrast, thiopental has less negative inotropic effects on hemodynamics compared to propofol, which could be suitable to prevent hypotension during GA induction. In the present age-stratified, randomized, assessor-blinded study, using the ClearSight® system, we compared the hemodynamic effects of propofol and thiopental during GA induction under remifentanil infusion in non-cardiac surgery. METHODS: Patients were divided into young (20-40 year), middle (41-70 year), and elderly (> 70 year) groups (n = 20, each group). General anesthesia was induced with remifentanil 0.3 µg/kg/min, followed by propofol (2.0, 1.5, and 1.2 mg/kg) or thiopental (5.0, 4.0, and 3.0 mg/kg) in the young, middle, and elderly groups, respectively. The primary outcome was the difference in the decrease in mean arterial blood pressure between patients receiving propofol and thiopental in each age group. The secondary outcomes included other hemodynamic parameters and minimal bispectral index values measured up to 10 min after tracheal intubation. RESULTS: The decrease in mean arterial blood pressure was greater in patients receiving propofol than those receiving thiopental (- 45.4 vs - 26.6 mmHg and - 45.7 vs - 28.9 mmHg, P = 0.003 and 0.007, respectively), whereas no significant difference was observed in the young age group (P = 0.96). CONCLUSIONS: Thiopental is a more suitable agent than propofol for avoiding hypotension during GA induction under remifentanil infusion in the middle and elderly patients.

The Sum of Early Diastolic Annulus Velocities in the Mitral and Tricuspid Valve Can Predict Adverse Events After Cardiac Surgery.

OBJECTIVES: To assess whether a tissue Doppler imaging (TDI)-based parameter consisting of the sum of early diastolic velocities of the mitral annulus (Me') and tricuspid annulus (Te') can serve as a predictor of adverse outcomes after cardiac surgery. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: The study comprised 100 patients undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After anesthetic induction, transesophageal echocardiography was performed to obtain the values of the early transmitral flow velocity (E), Me', and Te'. The primary endpoint was the incidence of postoperative major organ morbidity and mortality (MOMM) events, including death, redo surgery, prolonged ventilation, stroke, sternal infection, and dialysis. Receiver operating characteristic and multivariate logistic analyses were used to examine the prognostic performance of TDI-based parameters for predicting MOMM incidence. The secondary endpoint was the incidence of death or rehospitalization for cardiovascular disease within 1 year post-discharge. TDI-based parameters were measured in 87 of the 100 patients enrolled. Me' plus Te' had better prognostic ability (area under the curve 0.771; threshold 13 cm/s; sensitivity 86.7%; specificity 64.9%) than that of Me' or E to Me' (E/Me')% and was an independent predictor of MOMM (odds ratio 0.45; 95% confidence interval 0.28-0.74, p = 0.001), whereas Me' was not. Lower Me' plus Te' (≤13 cm/s) was associated with a significantly higher incidence and earlier onset of cardiovascular events within 1 year post-discharge (p = 0.012). CONCLUSIONS: Compared with Me' and E/Me', which traditionally are used for assessing diastolic function, Me' plus Te' showed better prognostic ability for both short- and long-term outcomes of cardiac surgery.

Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin.

Human P-cadherin is a cell adhesion protein of the family of classical cadherins, the overexpression of which is correlated with poor prognosis in various types of cancer. Antibodies inhibiting cell-cell adhesion mediated by P-cadherin show clear therapeutic effect, although the mechanistic basis explaining their effectiveness is still unclear. Based on structural, physicochemical, and functional analyses, we have elucidated the molecular mechanism of disruption of cell adhesion by antibodies targeting human P-cadherin. Herein we have studied three different antibodies, TSP5, TSP7, and TSP11, each recognizing a different epitope on the surface of the cell-adhesive domain (EC1). Although all these three antibodies recognized human P-cadherin with high affinity, only TSP7 disrupted cell adhesion. Notably, we demonstrated that TSP7 abolishes cell adhesion by disabling the so-called X-dimer (a kinetic adhesive intermediate), in addition to disrupting the strand-swap dimer (the final thermodynamic state). The inhibition of the X-dimer was crucial for the overall inhibitory effect, raising the therapeutic value of a kinetic intermediary not only for preventing, but also for reversing, cell adhesion mediated by a member of the classical cadherin family. These findings should help to design more innovative and effective therapeutic solutions targeting human P-cadherin.

Usefulness and growing need for intraoperative transthoracic echocardiography: a case series.

BACKGROUND: Physician-performed transthoracic echocardiography (TTE) is still seldom used during anesthesia. Despite its various advantages, there are only a few reports of intraoperative TTE. We report 3 cases in which intraoperative TTE was successfully used. CASE PRESENTATION: A 75-year-old woman (Case 1) was scheduled for a posterior spinal fusion. When the wound was being closed, systolic blood pressure suddenly dropped to 30 mmHg. TTE revealed hypokinesis in the antero-septal region. Emergent coronary angiography showed 90% stenosis in left anterior descending artery (Segment 7), and a bare metal stent was implanted. A 71-year-old woman (Case 2) with hypertrophic cardiomyopathy was scheduled for brain tumor operation. During anesthesia induction, the patient developed hemodynamic instability. TTE showed systolic anterior motion of the mitral valve, and appropriate treatment was administered. A 78-year-old woman (Case 3) was scheduled for revision total hip arthroplasty. When the wound was closed, TTE revealed severe hypovolemia despite massive infusion. We insisted on reopening the wound and found additional massive hemorrhage. CONCLUSION: Intraoperative TTE is a potent tool for quick hemodynamic evaluation because it is noninvasive and has sufficient diagnostic capabilities. The successful outcomes of our cases suggest the great usefulness of intraoperative TTE, and more frequent use is to be encouraged.

Improved Performance of the Fourth-Generation FloTrac/Vigileo System for Tracking Cardiac Output Changes.

OBJECTIVES: The aims of this study were to compare cardiac output (CO) measured by the new fourth-generation FloTrac™/Vigileo™ system (Version 4.00) (COFVS) with that measured by a pulmonary artery catheter (COREF), and to investigate the ability of COFVS to track CO changes induced by increased peripheral resistance. DESIGN: Prospective study. SETTING: University Hospital. PARTICIPANTS: Twenty-three patients undergoing cardiac surgery. INTERVENTIONS: Phenylephrine (100 µg) was administered. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, including CO(REF) and CO(FVS), were measured before and after phenylephrine administration. Bland-Altman analysis was used to assess the discrepancy between CO(REF) and CO(FVS). Four-quadrant plot and polar-plot analyses were utilized to evaluate the trending ability of CO(FVS) against CO(REF) after phenylephrine boluses. One hundred thirty-six hemodynamic interventions were performed. The bias shown by the Bland-Altman analysis was-0.66 L/min, and the percentage error was 55.4%. The bias was significantly correlated with the systemic vascular resistance index (SVRI) before phenylephrine administration (p<0.001, r(2) = 0.420). The concordance rate determined by four-quadrant plot analysis and the angular concordance rate calculated using polar-plot analysis were 87.0% and 83.0%, respectively. Additionally, this trending ability was not affected by SVRI state. CONCLUSIONS: The trending ability of the new fourth-generation FloTrac™/Vigileo™ system after increased vasomotor tone was greatly improved compared with previous versions; however, the discrepancy of the new system in CO measurement was not clinically acceptable, as in previous versions. For clinical application in critically ill patients, this vasomotor tone-dependent disagreement must be decreased.

Discrepancy between superior vena cava oxygen saturation and mixed venous oxygen saturation can predict postoperative complications in cardiac surgery patients.

OBJECTIVE: To determine if increases in discrepancy between ScvO2 and SvO2 (ScvO2 - SvO2 = ΔSO2) during surgery in cardiac surgery patients can predict postoperative complications. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: One hundred two patients undergoing cardiac surgery were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) values during surgery automatically were collected. The average value of ΔSO2 for every minute was calculated. The area under the receiver operating characteristic curve for prolonged postoperative ICU stay (≥3 days) was 0.745 for ΔSO2, which was significantly different from those of ScvO2 and SvO2 (p<0.05) (ScvO2; 0.584, SvO2; 0.598). The optimal threshold value of ΔSO2 to predict prolonged ICU stay (≥3 days) was 12% (sensitivity: 72.0%, specificity: 76.9%). Postoperative ICU duration, ventilation time, and hospital stay were significantly longer in Group D patients (intraoperative maximum ΔSO2 ≥12%) than those in Group N patients (intraoperative maximum ΔSO2<12%). As for postoperative complications, the number of patients with postoperative use of intra-aortic balloon pumping, delirium, respiratory failure requiring tracheotomy, and severe complications was significantly higher in Group D patients. Multivariate logistic regression models were used to evaluate the independent effects of perioperative variables on the risk of developing prolonged ventilation (>24 hours) and prolonged ICU stay (≥3 days). A discrepancy in intraoperative ΔSO2 was an independent risk factor for prolonged postoperative ventilation and ICU stay. CONCLUSION: The discrepancy between ScvO2 and SvO2 during cardiac surgery is an independent risk factor of postoperative complications such as prolonged ICU stay and ventilation time.

Structural and thermodynamic characterization of the self-adhesive properties of human P-cadherin.

Human P-cadherin is a promising therapeutic target against cancer. However, its characterization at the molecular level is still lacking. We report that human P-cadherin associated irreversibly in a distinct dimer configuration. Unexpectedly, the divalent cation Ca²âº was not necessary for dimerization, although it greatly stabilized the protein-protein complex.

The effect of dexmedetomidine on electrocorticography in patients with temporal lobe epilepsy under sevoflurane anesthesia.

BACKGROUND: Although dexmedetomidine is often used in neuroanesthesia and neuronal critical care practice, its effect on cerebral electrical activity in those with an abnormal electroencephalogram is not known. The electrocorticogram (ECoG), a sensitive method for examining the effect of drugs on cerebral electrical activity and surgical treatment for epilepsy, is usually guided by monitoring of the ECoG. We investigated the effect of dexmedetomidine on ECoG in patients with epilepsy undergoing surgery with sevoflurane. METHODS: Patients with medically intractable temporal lobe epilepsy undergoing resection of the epileptic foci (n = 11) were enrolled. Under general anesthesia with 2.5% sevoflurane and end-tidal carbon dioxide tension at 30 mm Hg, ECoG was recorded by strip electrodes with eight contacts placed on the mesial temporal lobe ipsilateral to the epilepsy foci. Dexmedetomidine was given as a computer-controlled infusion to achieve target plasma concentrations of 0.5 and 1.5 ng/mL. Each concentration was maintained for 20 min and ECoG was recorded before infusion of dexmedetomidine and between the 10th and 20th min after starting infusion. The median frequency of ECoG, spectral power density of each spectral band, and number of spikes at each concentration of dexmedetomidine were compared by Kruskal-Wallis test, followed by Student-Newman-Keuls test. RESULTS: The median frequency of ECoG in 88 leads from all leads from all patients was significantly decreased by 1.5 ng/mL of dexmedetomidine compared with those at baseline and 0.5 ng/mL (P = 0.003 and 0.03, respectively); however, spectral power densities in the frequency bands: delta (<4 Hz), theta (> or =4 and <8 Hz), alpha (> or =8 and <13 Hz), and beta (> or =13 Hz), were not changed. Neither the number of leads with spikes nor the number of spikes in all leads and in the lead with highest number of spikes at baseline was affected by dexmedetomidine. CONCLUSIONS: Dexmedetomidine at plasma concentrations of 0.48 and 1.60 ng/mL decreased the median frequency of ECoG, but did not affect spike activity in patients with temporal lobe epilepsy anesthetized with 2.5% sevoflurane.

Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic obstructive pulmonary disease severity.

BACKGROUND AND OBJECTIVE: COPD is a multifactorial disease influenced by genetic and environmental factors, and gene-by-environmental interactions. There is considerable variability in the degree of airflow obstruction, moreover only 10-15% of chronic smokers develop COPD. These observations indicate that additional risk factors, possibly genetic, contribute to not only the susceptibility to COPD but also the development and severity of COPD. Recent paradigms highlight the presence and causal role of apoptosis in emphysema. There is a large amount of information on the genes involved in the regulation of apoptosis and one of the most studied is Bcl-2. The aim of this study was to investigate the genetic association of Bcl-2 gene with the level of lung function, that is, the severity, of COPD. METHODS: The genetic association of Bcl-2 polymorphisms with lung function was investigated in 261 Japanese patients with COPD using 12 single-nucleotide polymorphisms (SNPs) in Bcl-2. RESULTS: Four SNPs showed a significant association between the high and low lung function groups in a dominant trait comparison. Subsequent linkage-disequilibrium mapping and analyses of haplotype structure also showed a significant association between the level of lung function and two haplotypes comprised of the associated SNPs in Bcl-2. CONCLUSIONS: Although the linkage between Bcl-2 gene and the susceptibility to COPD remains to be clarified, the findings of the current study indicate that Bcl-2 might be influencing the level of lung function, that is, the development and severity of COPD.