Age progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.

BACKGROUND: Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task. METHODS: Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (Cp) to gradually reach 3.5 µg mL-1 over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis. RESULTS: Age was significant covariate for baseline BIS effect (E0), inhibitory propofol concentration at 50% BIS decline (IC50) and maximum BIS decline (Emax). First-order rate constant Ke0 of 0.47 min-1 in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min-1 in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended Cp of 3.5 µg mL-1 for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year. CONCLUSION: We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol Cp of 3.5 µg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 3.5 µg mL-1 for 20-29 year should be gradually decreased to 2.0 µg mL-1 for 80-89 year. CLINICAL TRIAL REGISTRY NUMBERS: European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

AIMS: The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). METHODS AND RESULTS: One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P < 0.001) indicative of GORD, intestinal metaplasia (P < 0.001), and an endoscopic diagnosis of oesophagitis (P < 0.001). No association with an endoscopic diagnosis of Barrett's oesophagus or with gastric pathology, particularly Helicobacter infection, was observed. CONCLUSIONS: Cardiac mucosa is a common finding in biopsy specimens taken from the gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion.

The second Austrian benchmark study for blood use in elective surgery: results and practice change.

BACKGROUND: Five years after the first Austrian benchmark study demonstrated relatively high transfusion rate and an abundance of nonindicated transfusions in elective surgeries, this study was conducted to investigate the effects of the first benchmark study. STUDY DESIGN AND METHODS: Data from 3164 patients undergoing primary unilateral total hip replacement (THR), primary unilateral noncemented total knee replacement (TKR), or coronary artery bypass graft (CABG) surgery at 15 orthopedic and six cardiac centers were collected and compared with the first study. RESULTS: Transfusion rates decreased in THR (41% to 30%) and TKR (41% to 25%), but remained unchanged in CABG surgery (57% vs. 55%) compared with the first study. More than 80% of all transfusions involved at least 2 units of red blood cells (RBCs). Marked variations were observed in transfusion rates among the centers. The prevalence of anemia was three times higher in patients who received transfusions versus those who did not. However, preoperative anemia was left untreated in the majority of patients. A considerable intercenter variability of RBC loss ranging from 26% to 43% in THR, from 24% to 40% in TKR, and from 30% to 49% in CABG procedures was observed. CONCLUSION: The second benchmark study demonstrates substantial intercenter variability and small but significant reductions in RBC transfusions and RBC loss. Even though the main independent predictors of transfusion were the relative lost RBC volume followed by the relative preoperative and the lowest relative postoperative hemoglobin, preoperative anemia was not adequately treated in many patients, underscoring the importance of patient blood management in these patients.

Aminoterminal pro-B-type natriuretic peptide: heart or lung disease in the neonate?.

OBJECTIVES: B-type natriuretic peptides have been shown to enable differentiation between heart and lung diseases in adults and children. In neonates, the role of natriuretic peptides for diagnosis of congenital heart defect (CHD) is not yet ascertained. The purpose of this single-center prospective study was to investigate aminoterminal B-type natriuretic peptide concentrations and their time courses during the first 5 days of life in neonates with CHD compared with neonates with respiratory distress. DESIGN: Single-center prospective study. SETTING: Tertiary-care neonatal ICU. PATIENTS: Aminoterminal B-type natriuretic peptide levels of 40 neonates with arterial duct-dependent CHD and of 40 neonates with respiratory distress without CHD were analyzed on the first, second, third, and fifth day of life. MAIN RESULTS: Mean aminoterminal B-type natriuretic peptide concentrations in the CHD group were significantly higher on the second (14191 vs. 4872 pg/mL), third (17790 vs. 3524 pg/mL), and fifth day (17015 vs. 4044 pg/mL), but not on the first day of life. Repeated measurements analysis of variance revealed a significantly different time course of aminoterminal B-type natriuretic peptide concentrations between the two groups. CONCLUSIONS: On the first day of life, aminoterminal B-type natriuretic peptide cannot differentiate between CHD and respiratory distress without CHD in the neonate. From the second day onwards, aminoterminal B-type natriuretic peptide in neonates with CHD shows higher values and a different time course and enables differentiation between CHD and respiratory distress due to other than cardiac reasons.

Early migration characteristics of a 180° porous-coated cup with 1-mm press fit.

INTRODUCTION: Evaluation of early cup movement is an important diagnostic tool to predict the likelihood of long-term implant loosening and clinical failure. The investigated cementless cup is clinically proven over 10 years, but there is a paucity of information that accurately describes the migration characteristics of this component. MATERIALS AND METHODS: We retrospectively analysed the clinical outcome and migration behaviour of 60 Pinnacle 100 shells after an average 3.8-year follow-up (range 2.1-5.4 years). For migration measurement, EBRA (Einzel-Bild-Röntgen-Analyse) digital software was applied. Clinical assessment was performed using the HHS, the UCLA score and the SF-36 health survey. RESULTS: The clinical outcome showed excellent results with a mean HHS of 95.4 (SD 7.1) and mean UCLA of 6.9 (SD 1.3). All implants were radiologically stable within the observation period and none of the cups was at risk for aseptical loosening. EBRA analysis revealed a mean total migration of 1.4 mm (SD 0.9) (95 % CI 1.1-1.6) at 3 years. Eight cups migrated more than 1 mm within the first three postoperative months, thereafter the migration curves flattened down. CONCLUSION: Surgeons may expect to find a variable amount of early migration when using the Pinnacle cup. To our knowledge, these are the first results, which show an early "impaction" of a cementless cup, followed by subsequent osseointegration. We believe that an appropriate long-term outcome of the investigated cup is ensured. The data of the present investigation will provide clinicians with useful baseline information with which to compare new cup designs.

Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting.

BACKGROUND: Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node-negative patients and compared routine and review pathology diagnoses. METHODS: In total, 381 tumors from randomly selected patients were retrospectively reviewed. The presence of vascular invasion was related to disease-free and cancer-specific survival using the Kaplan-Meier method. For multivariable analysis, Cox proportional hazards regression models were performed. RESULTS: Lymphatic invasion and venous invasion were observed in 126 patients (33%) and 87 patients (23%), respectively, and were associated significantly with tumor classification, lymph node status, American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) disease stage, tumor differentiation, pattern of invasion, and extent of tumor budding. The detection of vascular invasion was related to the number of examined tissue blocks. Venous and lymphatic invasion proved to be significant prognostic variables in univariable and multivariable analyses. Extramural vascular involvement was of particular significance. When the analysis was restricted to patients with (AJCC/UICC) stage II disease, venous invasion, but not lymphatic invasion, was identified as an independent prognostic variable. Review pathology diagnoses differed significantly from routine diagnoses with respect to prognostic impact. CONCLUSIONS: Venous and lymphatic invasion proved to be significant prognostic variables in patients with CRC. The detection of vascular invasion and, consequently, risk stratification of affected patients were related to the quality of pathology workup, ie, the number of examined tissue blocks. Observed differences between review and routine pathology diagnoses illustrated the need for high-quality pathology reporting and also for standardized quality control.

Tumor budding is an independent predictor of outcome in AJCC/UICC stage II colorectal cancer.

BACKGROUND: In colorectal cancer, the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth, thus providing important prognostic information. The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage II disease. METHODS: Tumors of 120 randomly selected patients with AJCC/UICC stage II disease were retrospectively reviewed for tumor growth pattern (expanding vs. infiltrating) and the extent of tumor budding, with high-grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin. Progression-free and cancer-specific survivals were determined by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. RESULTS: The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion, while high-grade budding was significantly associated with tumor grade and lymphovascular invasion. High-grade budding, but not the infiltrating growth pattern, was significantly associated with outcome in univariable analysis. Cox's proportional hazards regression models proved tumor budding to be an independent predictor of disease progression (hazard ratio 3.91, 95 % confidence interval 1.3-11.77; P = 0.02) and cancer-related death (hazard ratio 5.90, 95 % confidence interval 1.62-21.51; P = 0.007). The combination of infiltrating growth pattern and high-grade budding did not have a stronger prognostic significance than tumor budding alone. CONCLUSIONS: Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication, patient counseling, and design of clinical trials by using integrated multimodal therapy.

Mucinous differentiation in colorectal cancer--indicator of poor prognosis?

AIMS: To analyse the prognostic impact of mucinous differentiation in colorectal mucinous adenocarcinomas and adenocarcinomas with a mucinous component. METHODS AND RESULTS: A total of 381 tumours were reviewed for mucinous differentiation by two independent pathologists. Mismatch repair status was assessed by immunohistochemistry. Prognostic significance was assessed by univariate and multivariate analyses. Eighty-one (21%) tumours were Union Internationale Contre le Cancer (UICC) Stage I, 120 (31%) Stage II, 126 (33%) Stage III and 54 (14%) Stage IV. Mucinous adenocarcinomas accounted for 12% and adenocarcinomas with a mucinous component for 19% of tumours. Mucinous differentiation was associated significantly with mismatch repair protein deficiency. The presence of extracellular mucin, regardless of extent, did not affect patients' outcome, while tumour grade, vascular and perineural invasion, tumour border configuration and budding were associated significantly with outcome. Cox analysis proved venous invasion to be an independent predictor of outcome in mucinous adenocarcinomas and both venous invasion and tumour budding as independent predictors of outcome in adenocarcinomas with any amount of mucin. CONCLUSIONS: Mucinous adenocarcinomas and/or adenocarcinomas with mucinous component do not differ from conventional adenocarcinomas with respect to prognosis and histological predictors of outcome. Hence, recording of mucinous differentiation may be used as an indicator of mismatch repair deficiency, but not for prognostic stratification.

Levosimendan versus milrinone in neonates and infants after corrective open-heart surgery: a pilot study.

OBJECTIVE: Low cardiac output syndrome commonly complicates the postoperative course after open-heart surgery in children. To prevent low cardiac output syndrome, prophylactic administration of milrinone after cardiopulmonary bypass is commonly used in small children. The aim of this study was to compare the effect of prophylactically administered levosimendan and milrinone on cardiac index in neonates and infants after corrective open-heart surgery. DESIGN: Prospective, single-center, double-blind, randomized pilot study. SETTING: Tertiary care center, postoperative pediatric cardiac intensive care unit. PATIENTS: After written informed consent, 40 infants undergoing corrective open-heart surgery were included. INTERVENTIONS: At weaning from cardiopulmonary bypass, either a 24-hr infusion of 0.1 µg/kg/min levosimendan or of 0.5 µg/kg/min milrinone were administered. Cardiac output was evaluated at 2, 6, 9, 12, 18, 24, and 48 hrs after cardiopulmonary bypass using a transesophageal Doppler technique (Cardio-QP, Deltex Medical, Chichester, UK). Cardiac index was calculated from cardiac output and the patients' respective body surface area. RESULTS: Intention-to-treat data of 39 patients (19 in the levosimendan and 20 in the milrinone group) were analyzed using analysis of variance for repeated measurements for statistics. Analysis of variance revealed for both, cardiac index and cardiac output, similar results with no significant differences of the factors group and time. A significant interaction for cardiac output (p = .005) and cardiac index (p = .007) was found, which indicates different time courses of cardiac index in the two groups. Both drugs were well tolerated; no death or serious adverse event occurred. CONCLUSIONS: In our small study, postoperative cardiac index over time was similar in patients with prophylactically administered levosimendan and patients with prophylactically given milrinone. We observed an increase in cardiac output and cardiac index over time in the levosimendan group, whereas cardiac output and cardiac index remained stable in the milrinone group. This pilot study has primarily served to obtain experience using the new drug levosimendan in neonates and infants and to initiate further multicenter trials in pediatric patients.

Subsidence of a cementless femoral component influenced by body weight and body mass index.

PURPOSE: This trial was designed to evaluate the impact of physical characteristics such as body mass index, body weight and height on distal stem migration of a cementless femoral component, as the influence of obesity on the outcome of THA is still debated in literature and conflicting results have been found. METHODS: In this retrospective cohort study, migration patterns for 102 implants were analysed using the Einzel-Bild-Roentgen-Analyse (EBRA-FCA, femoral component analysis). In all cases the Vision 2000 stem was implanted and combined with the Duraloc acetabular component (DePuy, Warsaw, Indiana). RESULTS: The mean follow-up was 93 months. EBRA-FCA evaluations revealed a mean subsidence of 1.38 mm after two years, 2.06 mm after five and 2.24 mm after seven years. Five stems loosened aseptically. Correlation between increased migration over the whole period and aseptic loosening was highly significant (p < 0.001). Surgical technique had a significant influence on migration and stem stability (p = 0.002) but physical patient characteristics such as body weight over 75 kg and height over 165 cm also significantly influenced stem subsidence towards progressive migration (p = 0.001, p < 0.001). However, a high BMI did not trigger progressive stem migration (p = 0.87). Being of the male gender raised the odds for increased migration (p = 0.03). CONCLUSION: Physical characteristics such as body weight and height showed significant influence on migration patterns of this cementless femoral component. The operating surgeon should be aware that body weight above 75 kg and height over 165 cm may trigger increased stem migration and the surgeon should aim to fit these prostheses as tightly as possible. However this study demonstrates that a high BMI does not trigger progressive stem migration. Further investigations are needed to confirm our findings.

External validation of the Leibovich prognosis score for nonmetastatic clear cell renal cell carcinoma at a single European center applying routine pathology.

PURPOSE: The Leibovich prognosis score was developed as a prognostic tool for metastatic disease after radical nephrectomy for clear cell renal cell carcinoma using pathology review. However, this scoring system has never been externally validated. We externally validated its prognostic accuracy using routine pathology reports. MATERIALS AND METHODS: We retrospectively evaluated data from the routine pathology records of 1,754 consecutive patients with nonmetastatic clear cell renal cell carcinoma operated on between 1984 and 2006 at a single tertiary academic center. Clear cell renal cell carcinoma cases were categorized as 0 to 11 by the Leibovich prognosis score and further stratified into low, intermediate and high risk groups. Metastasis-free survival was assessed using the Kaplan-Meier method. To evaluate the prognostic impact a multivariate Cox regression model was used and prognostic accuracy was determined using Harrell's concordance index. RESULTS: Median followup was 82 months (IQR 39-142). Metastasis developed in 375 of the 1,754 patients (21.4%). The 10-year metastasis-free survival rate for Leibovich scores in our study ranged from 95% for scores of 0 and 1 to 12% for scores of 8 or greater. Pathological T stage, N stage, low tumor grade, large tumor diameter and histological tumor necrosis were independent predictors of metastasis-free survival (p <0.001). Harrell's concordance index was 0.778. CONCLUSIONS: Risk prediction by the Leibovich prognosis score using routine pathological results was comparable to that of the original data based on pathology review. Our data support using the Leibovich prognosis score in clinical practice for followup decisions and patient selection for adjuvant treatment trials.

Keratin 7 expression in colorectal cancer--freak of nature or significant finding?

AIMS: To assess the prevalence of keratin 7 (K7) expression in colorectal cancer and to correlate findings with clinicopathological parameters and patients' outcome. METHOD AND RESULTS: A total of 370 patients were evaluated for K7 expression by immunohistochemistry using a tissue microarray technique. K7 expression was scored semiquantitatively as either focal (<10%), moderate (10-50%) or extensive (>50%). In all, 32 (9%) tumours were immunoreactive for K7, with five cases showing extensive, four moderate and 23 focal expression, respectively. K7 expression was associated with poor tumour differentiation (P = 0.005) and the extent of tumour budding (P = 0.02). In whole sections, K7 immunoreactivity prevailed in single cells and small clusters of cells at the invasion front. Analysis of serial sections showed that K7-positive cells colocalized with keratin 20, whereas they lacked immunoreactivity for E-cadherin, MUC2 and MIB-1. Disease progression occurred in 52% of patients with K7-positive tumours and 41% with K7-negative tumours (P = 0.19); 48% of patients with K7-positive tumours but only 33% with K7-negative tumours died of disease (P = 0.06). CONCLUSIONS: Aberrant expression of K7 in budding cancer cells represents a modification of the epithelial phenotype ('epithelial-epithelial transition': EET) which may be linked to gains in motility and invasive potential.

[Patient blood management (part 1) - patient-specific concept to reduce and avoid anemia, blood loss and transfusion]. / Patient Blood Management (Teil 1) - Individuelles Behandlungskonzept zur Reduktion und Vermeidung von Anämie, Blutverlust und -Transfusionen.

Patient blood management (PBM) is a patient-specific multidisciplinary, multimodal, evidence-based concept to appropriately conserve and manage a patient's own blood as a vital resource. PBM is based on 3 pillars: the first is the optimization of the patient's endogenous red cell mass, the second is the minimization of bleeding and blood loss and the third involves harnessing and optimizing the patient-specific physiological tolerance of anemia, including adopting more restrictive transfusion thresholds. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures and the escalating costs associated with transfusion. PBM is applicable to surgical and medical patients. The application of PBM systematically reduces the impact of 3 major contributors to negative outcome: anemia, blood loss and transfusion.

[Patient blood management (part 2). Practice: the 3 pillars]. / Patient Blood Management (Teil 2). Praktisches Vorgehen: die 3 Säulen.

Patient blood management (PBM) is a patient-specific multidisciplinary, multimodal, evidence-based concept to appropriately conserve and manage a patient's own blood as a vital resource. PBM is based on 3 pillars: the first is the optimization of the patient's endogenous red cell mass, the second is the minimization of bleeding and blood loss and the third involves harnessing and optimizing the patient-specific physiological tolerance of anemia, including adopting more restrictive transfusion thresholds. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures and the escalating costs associated with transfusion. PBM is applicable to surgical and medical patients. The application of PBM systematically reduces the impact of 3 major contributors to negative outcome: anemia, blood loss and transfusion.

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases.

The role of human prolactin and its receptor, the prolactin receptor, in colorectal cancer is largely unknown. Our study aimed to assess the prevalence of prolactin receptor expression, its association with clinicopathological variables, as well as its prognostic value, comparing results of primary tissues with those of corresponding metastases. In all, 373 primary colorectal cancer and 171 corresponding metastases were evaluated for prolactin receptor expression by immunohistochemistry using a tissue microarray technique. Immunoreactivity was semiquantitatively scored as either focal (<10% of tumor cells positive), moderate (10-50%), or extensive (>50%). Prolactin receptor expression was related to clinicopathological parameters as well as patient outcome. To substantiate our findings, prolactin receptor expression was additionally assessed in HT-29 and SW-480 colorectal cancer cell lines using western blot. Prolactin receptor expression was observed in 360 out of 373 (97%) primary tumors, with 21 (6%) cases showing focal, 55 (15%) moderate, and 284 (76%) extensive expression, respectively. Extensive prolactin receptor expression was significantly associated with tumor size (P=0.002) and grade (P<0.001) as well as histological subtype (P<0.001). Somer's D coefficients for concordance of primary tumors with corresponding lymph node and distant metastases were D=0.719 (P<0.001) and D=0.535 (P=0.001), respectively. Extensive prolactin receptor expression was significantly associated with disease progression (P=0.03) and cancer-specific survival (P=0.04) in patients with high-grade cancers. In conclusion, prolactin receptor expression is common in colorectal cancer, with high concordance between primary tumors and corresponding metastases. In view of evolving targeted therapy concepts in colorectal cancer, widespread prolactin receptor expression may offer a therapeutic perspective in affected patients.

BIS-vista occipital montage in patients undergoing neurosurgical procedures during propofol-remifentanil anesthesia.

BACKGROUND: Neurosurgical procedures that require a frontal approach could be an impediment for a successful Bispectral Index (BIS) frontal sensor placement. The aim of this study was to explore the utility of using the new BIS-Vista monitor (Aspect Medical Systems, Newton, MA) for occipital sensor placement in the patients undergoing brain neurosurgical procedures during propofol-remifentanil anesthesia. METHODS: Two BIS Quatro sensors (Aspect Medical Systems, Newton, MA) mounted on the occipital and frontal regions were connected to two BIS-Vista monitors at three anesthesia states: before induction, during anesthesia maintenance, and recovery. RESULTS: There were significant differences before induction (P = 0.0002) and at anesthesia maintenance (P = 0.0014) between mean +/- SD occipital (83.4 +/- 4.8, 66.7 +/- 7.2) and frontal (93.1 +/- 3.4, 56.9 +/- 9.1) BIS-Vista values. During anesthesia recovery, there was no difference (P = 0.7421) between occipital (54.6 +/- 9.3) and frontal (53.1 +/- 7.3) BIS-Vista values. Bland and Altman analysis revealed a BIS-Vista negative-bias (limits of agreement) of -9.7 (+1.1, -20.5) before anesthesia induction, +9.8 positive-bias (+22.8, -1.7) during anesthesia maintenance, and -0.9 bias (+10.9, -12.8) during anesthesia recovery. CONCLUSION: We demonstrated that not only the regional limits of agreement are too wide to allow data of the two montages to be used interchangeably but also the variation is a function of anesthetic depth. However, keeping in mind a relatively consistent BIS-Vista -10 bias before induction and +10 bias during anesthesia maintenance with limits of agreement of approximately +/-11 BIS units, approximately double the clinically acceptable less than 10 BIS units level of agreement, BIS-Vista off-label occipital montage might be helpful in following a trend of propofol-remifentanil anesthesia in individual cases where frontal access is particularly difficult.

Clinical significance of pT sub-classification in surgical pathology of colorectal cancer.

PURPOSE: Tumour stage is the strongest prognostic parameter in colorectal cancer. The study aimed to evaluate the prognostic impact of pT2, pT3, and pT4 sub-classification. METHODS: Three hundred eighty-one surgical colorectal cancer specimens were retrospectively re-evaluated. pT2 tumours were sub-classified according to infiltration of the inner circumferential (pT2a) or outer longitudinal (pT2b) layer of the muscularis propria. pT3 tumours were sub-classified by measuring the maximal tumour invasion beyond the outer border of the muscularis propria (pT3a 1-5 mm, pT3c > 5-15 mm, and pT3d > 15 mm). pT4 tumours were sub-classified according to invasion of other organs or structures (pT4a) or perforation of the visceral peritoneum (pT4b). Data were correlated with other pathological parameters and patient outcome. RESULTS: Seventy pT2 tumours were re-classified as 37 pT2a and 33 pT2b tumours. There was no significant association with tumour grade, angioinvasion, or lymph node involvement and no significant impact on prognosis. Two hundred eighteen pT3 tumours were re-classified as 49 pT3a, 83 pT3b, 53 pT3c, and 33 pT3d tumours. pT3 sub-classification was significantly associated with tumour grade, angioinvasion, and lymph node involvement and proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. A cut-off level of 5 mm is recommended. Sixty-five pT4 tumours were re-classified as 15 pT4a and 50 pT4b tumours. There was no significant association with tumour grade, angioinvasion, or lymph node involvement and no significant impact on prognosis. CONCLUSIONS: pT3 sub-classification was significantly associated with patient outcome. In contrast, pT2 and pT4 sub-classification did not show clinical significance.

Premature preoperative discontinuation of antiplatelet drug therapy in cardiovascular risk patients: a preliminary study on the role of P2Y12 receptor monitoring.

BACKGROUND AND OBJECTIVE: In high-bleeding risk procedures, discontinuation of antiplatelet drug therapy with clopidogrel may be requested by surgeons, usually 7-10 days before the surgical procedure. New platelet function tests, such as the vasodilator-stimulated phosphoprotein phosphorylation assay, may help to assess the perioperative status of the clopidogrel-specific P2Y12 receptor. METHODS: Using vasodilator-stimulated phosphoprotein phosphorylation assay, the platelet reactivity index (PRI) was measured in 80 individuals, including 20 healthy volunteers, 20 cardiologic patients under full antiplatelet drug therapy with clopidogrel and aspirin, 20 surgical patients without any antiplatelet drugs and 20 patients under clopidogrel, discontinued 7 days before the surgical procedure. RESULTS: The mean PRI (95% confidence interval) in healthy volunteers was 86 (82-89%) and that in the surgical control group was 77% (72-81%). In cardiologic patients under full antiplatelet therapy, mean PRI was 51% (42-60%). In the clopidogrel discontinuation group, PRI increased from 51% (40-62%) on day 0 to 65% (57-74%) on day 3 and to 76% (69-84%) on day 5. On the morning of surgery, mean PRI was 85% (80-91%). The PRI values on the 5th day were equivalent to those of the surgical control group (mean difference -0.4%, 95% confidence interval -8.6% to 7.8%, P = 0.9). Fifty-five percent of the patients in the discontinuation group had a PRI of more than 50% on day 0. CONCLUSION: The study using vasodilator-stimulated phosphoprotein phosphorylation assay, one of the new platelet function assays for the assessment of inhibition of platelet P2Y12 receptor, demonstrates that the PRI on day 5 after discontinuation of clopidogrel is equivalent to a surgical control group and it questions the rigid practice of delaying surgery for 7-10 days, particularly in patients without a clopidogrel effect.

Measurement of cardiac output and pulmonary transit time for assessment of pulmonary vascular resistance in domestic piglets.

The degree of elevated pulmonary vascular resistance (PVR) is a crucial clinical parameter. Cardiac output (CO) and pulmonary transit time (PTT) can be ascertained by a number of radiological methods. A close functional relationship between CO, PTT and PVR would facilitate non-invasive PVR measurements. One-hundred and fifty-one measurements were made in six piglets. Pressures in the pulmonary and systemic circulation were measured invasively. Cardic output was determined by the use of a Doppler flow probe around the truncus pulmonalis. Temperature sensors were placed in the pulmonary truncus and left atrium. Elevated PVR was produced by repeated air embolism. After injection of ice-cold saline, the time span between the minimal temperature in the truncus pulmonalis and the left atrium was taken as PTT. The CO and PTT were inserted into a new formula derived from the Hagen-Poiseuille law for the calculation of the PVR model. Numerical constants of the formula were calculated by the robust method of minimization. The PVR values, as calculated from invasively measured mean pulmonary artery pressure, mean left atrial pressure and CO, served as reference. In the six piglets, the PVR model and PVR reference showed a strong linear correlation with r = 0.923. The Bland-Altman plot revealed a standard deviation of -0.64/+0.67 Wood units. Cardiac output, PTT and PVR showed a close functional relationship. With a correction for blood viscosity and body size, this relationship could be used for non-invasive clinical measurements of PVR.

Effect of flumazenil on bispectral index monitoring in unpremedicated patients.

BACKGROUND: Flumazenil is an imidazobenzodiazepine that promptly reverses via competitive inhibition the hypnotic/sedative effects of benzodiazepines on gamma-aminobutyric acid receptors. Endogenous benzodiazepine ligands (endozepines) were isolated in urine, cerebrospinal fluid, and breast milk of women who had not received benzodiazepines. The bispectral index (BIS), an electroencephalographically derived parameter widely used for monitoring the effects of anesthetic/hypnotic drugs, was shown to correlate to various conditions that could influence electroencephalography. The authors examined the hypothesis that 0.5 mg of flumazenil administered to healthy unpremedicated patients during deep surgical remifentanil/propofol anesthesia would increase the BIS value and might expedite recovery from anesthesia. METHODS: Sixty healthy unpremedicated patients were randomly allocated to the flumazenil or control groups. After study drug administration, the authors compared BIS values and various recovery parameters in the flumazenil and control groups. RESULTS: BIS baseline values in the flumazenil group (38.7 +/- 3.8) increased 15 min after flumazenil administration (53.2 +/- 4.7), with a significant difference over time (P < 0.0001) between the two groups. Mean recovery parameters time, comprising time to spontaneous breathing, eye opening/hand squeezing on verbal command, extubation, and date of birth recollection, was significantly shorter (P = 0.0002) in the flumazenil group (6.9 +/- 2.6 min) compared with the control group (9.8 +/- 2.9 min). CONCLUSIONS: This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.