Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24.

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.

Does grazing management provide opportunities to mitigate methane emissions by ruminants in pastoral ecosystems?

Agriculture, and livestock production in particular, is criticized for being a contributor to global environmental change, including emissions of greenhouse gases (GHG). Methane (CH4) from grazing ruminants accounts for most of livestock's carbon footprint because a large share of them are reared under suboptimal grazing conditions, usually resulting in both low herbage intake and animal performance. Consequently, the CH4 quota attributed to animal maintenance is spread across few or no animal outputs, increasing the CH4 intensity [g CH4/kg live weight (LW) gain or g CH4/kg milk yield]. In this review, the generalized idea relating tropical pastures with low quality and intrinsically higher CH4 intensity is challenged by showing evidence that emissions from animals grazing tropical pastures can equal those of temperate grasses. We demonstrate the medium-to-high mitigation potential of some grazing management strategies to mitigate CH4 emissions from grazing ruminants and stress the predominant role that sward canopy structure (e.g., height) has over animal behavioral responses (e.g., intake rate), daily forage intake and resulting CH4 emissions. From this ecological perspective, we identify a grazing management concept aiming to offer the best sward structure that allows animals to optimize their daily herbage intake, creating opportunities to reduce CH4 intensity. We show the trade-off between animal performance and CH4 intensity, stressing that mitigation is substantial when grazing management is conducted under light-to-moderate intensities and optimize herbage intake and animal performance. We conclude that optimizing LW gain of grazing sheep and cattle to a threshold of 0.14 and 0.7 kg/day, respectively, would dramatically reduce CH4 intensity to approximately 0.2 kg CH4/kg LW gain, as observed in some intensive feeding systems. This could represent a mitigation potential of around 55% for livestock commodities in pasture-based systems. Our results offer new insights to the debate concerning mitigation of environmental impacts of pastoral ecosystems.

Potential of grazing management to improve beef cattle production and mitigate methane emissions in native grasslands of the Pampa biome.

We tested the hypothesis that improving sward structure through adjustments in forage allowance results in greater forage intake and live weight (LW) gains by beef cattle and lower CH4 emissions per unit LW gain and unit area in a native grassland ecosystem of the Pampa biome. The experiment was carried out during 2012 and 2013 in southern Brazil. The experimental design was a randomized complete block with two replicates. Treatments consisted of five contrasting forage allowances of a native grassland managed under continuous stocking: 4, 8, 8-12, 12, and 16 kg of dry matter (DM) 100 kg LW-1 day-1 (or % LW). The 8-12% LW treatment had a variable forage allowance of 8% LW in spring and 12% LW in summer, autumn, and winter. Forage allowance was controlled by changes in stocking rate (kg LW ha-1). Average daily gain (kg LW day-1) was high for forage allowances of 12 and 16% LW but decreased at 8%, reaching the lowest value at 4% LW treatment (p < 0.001). Live weight gain ha-1 year-1 was the greatest at forage allowance of 8-12% LW (p < 0.001). Forage DM intake peaked at a forage allowance of 12% LW (p = 0.005). Individual CH4 emissions remained constant around 150 g day-1 for the two highest forage allowances and decreased to 118 and 107 g day-1 under forage allowances of 8 and 4% LW, respectively (p = 0.002). Emissions per unit LW gain and unit area were driven by animal productivity changes and decreased with increasing forage allowance (p = 0.001 and p = 0.040, respectively). We propose that the combination of 8% LW forage allowance during spring and 12% LW during the rest of the year should be targeted to best balance animal production and environmental impact in the Pampa biome.

Epidural anesthesia improves outcome and resource use in cardiac surgery: a single-center study of a 1293-patient cohort.

Thoracic epidural anesthesia (TEA) combined with general anesthesia in cardiac surgery has the potential to initiate earlier spontaneous ventilation and extubation, improved hemodynamics, less arrhythmia or myocardial ischemia, and an attenuated neurohormonal response. The aim of the current study was to characterize the correlation between TEA and postoperative resource use or outcome in a consecutive-patient cohort. The study was performed in a tertiary care, 3-surgeon, university-affiliated hospital that performs 350 to 400 cardiac surgeries per year. All 1293 adult patients who underwent cardiac surgery between July 1, 2002, and February 1, 2006, were included. Patients were assigned to anesthesiologists practicing TEA (TEA group, n = 506) or not (control group, n = 787) for cardiac surgery. The preoperative parameter values and Parsonnet scores for the 2 groups were similar. The 2 groups had the same distribution of surgery types. The TEA group presented with fewer intensive care unit (ICU) complications, such as delirium, pneumonia, and acute renal failure, and presented with better myocardial protection. The TEA group presented with a higher proportion of immediately postoperative extubations and with shorter ventilation times and ICU stays. Total ICU costs decreased from US $18,700 to $9900 per patient. Combining TEA and general anesthesia for cardiac surgery allows a significant change in anesthesia strategy. This change improves immediate postoperative outcomes and reduces the use and costs of ICU resources.

A novel approach for pain management in cardiac surgery via median sternotomy: bilateral single-shot paravertebral blocks.

Regional analgesia has entered cardiac anesthesia in the form of spinal or epidural analgesia. However, the risk of spinal or epidural hematoma is a constant worry. Alternative regional techniques might be applicable in cardiac surgery. The purpose of this study is to present a novel technique of bilateral single-shot paravertebral blocks (BSS-PVB) for cardiac surgery via median sternotomy and compare its efficacy versus high thoracic epidural analgesia (TEA). Fifty-two patients were compared in this prospective cohort audit. In 26 patients, cardiac surgery was performed using low-dose fentanyl/BSS-PVB (bilateral blocks of 3 mL bupivacaine 0.5% each, T1-7) and general anesthesia; in another 26 patients, TEA (bupivacaine 0.125% at 10 mL/hour) and general anesthesia were used. Patients were assigned to cohorts according to their preoperative data and types of surgery. All patient data are shown as mean +/- SD; pain scores were compared between groups using the t test immediately, 6 hours, and 24 hours after surgery (P < .05). In the BSS-PVB-group (19 men, 7 women), mean age was 65 +/- 11 years, weight 74 +/- 16 kg, ejection fraction 59% +/- 12%, and duration of surgery 130 +/- 27 minutes; in the TEA-group (17 men, 9 women), mean age was 63 +/- 10 years, weight 75 +/- 16 kg, ejection fraction 58% +/- 12%, and duration of surgery 113 +/- 27 minutes. These data and preoperative comorbidity variables were not significantly different between the two groups. In each group, 18 patients underwent off-pump coronary artery bypass grafting, 3 on-pump and 5 mitral valve replacements. All patients were successfully immediately extubated. Postoperative pain scores were at any point significantly lower with TEA, immediately at 2.4 +/- 2.2 versus 3.7 +/- 2.6, at 6 hours at 1.1 +/- 1.5 versus 2.4 +/- 1.8, and at 24 hours at 1.0 +/- 1.4 versus 2.3 +/- 1.6 (0 = no pain, 10 = maximum pain). There was no complications related to epidural catheter placement or BSS-PVB. Using both techniques, immediate extubation after cardiac surgery is feasible; TEA provides better pain relief after cardiac surgery than BSS-PVB.

Immediate Extubation after Aortic Valve Surgery Using High Thoracic Epidural Anesthesia.

Abstract Purpose: Fast-track anesthesia has gained widespread use in cardiac centers around the world. No study has focused on immediate extubation after aortic valve surgery. This study examines the feasibility and hemodynamic stability of immediate extubation after simple or combined aortic valve surgery using thoracic epidural anesthesia. Methods: Thirty patients undergoing aortic valve surgery with an ejection fraction of more than 30% were included in this prospective audit. After insertion of a high thoracic epidural catheter, induction with fentanyl 2 to 4 microg/kg, administration of propofol 1 to 2 mg/kg, and endotracheal intubation facilitated by rocuronium, anesthesia was maintained with sevoflurane titrated according to bispectral index (target, 50). Perioperative analgesia was provided by high thoracic epidural analgesia (TEA) (bupivacaine 0.125% 6-14 mL/h). Hemodynamic data were compared by Friedman test. P <.05 was considered to show a significant difference. Data are presented as median (25th-75th percentile). Results: Patients underwent simple aortic valve surgery (n = 17) or combined aortic valve surgery (n = 13) with additional coronary artery bypass grafting (n = 8), replacement of the ascending aorta (Bentall procedure) (n = 4), and repair of open foramen ovale (n = 1). All 30 patients were extubated within 15 minutes after surgery at 36.5 degrees C (36.4 degrees C-36.6 degrees C). There was no need for reintubation. Pain scores were low immediately after surgery and 6, 24, and 48 hours after surgery at 0 (0-3.5), 0 (0-2), 0 (0-2), and 0 (0-2), respectively. During and up to 6 hours after surgery, there was no significant hemodynamic change due to TEA. Fifteen of 30 patients needed temporary pacemaker activation. There were no complications related to TEA. Conclusions: Immediate extubation is feasible after aortic valve surgery with high thoracic epidural analgesia and maintenance of hemodynamic stability throughout surgery. Immediate extubation after aortic valve surgery is a promising new path in cardiac anesthesia.

Bispectral index as an indicator of cerebral hypoperfusion during off-pump coronary artery bypass grafting.

Bradycardia and hypotension are common during off-pump coronary artery bypass grafting (OPCAB). We present a case of possible reversible global cerebral hypoperfusion during distal grafting of the left circumflex coronary artery. The bispectral index (BIS) suddenly decreased from values of 45-50 to 0 during distal grafting. Neurologic evaluation after immediate tracheal extubation in the operating room was normal and the 58 yr old patient did not suffer any neurologic sequelae. Postoperative recovery was uneventful and the patient was discharged 5 days after surgery. Cerebral hypoperfusion is a possible complication during OPCAB. BIS monitoring in OPCAB could be an indicator of cerebral hypoperfusion.

Immediate extubation after aortic valve surgery using high thoracic epidural analgesia or opioid-based analgesia.

OBJECTIVE: Fast-track anesthesia has gained widespread use in cardiac centers around the world. No study has been published focusing on immediate extubation after aortic valve surgery. This study examines the feasibility and hemodynamic stability of immediate extubation after simple or combined aortic valve surgery using either thoracic epidural analgesia or opioid-based analgesia. DESIGN: Prospective audit, pilot study. SETTING: Single-institution university medical center. PARTICIPANTS: Adult patients undergoing aortic valve replacement (N = 45). INTERVENTIONS: Forty-five patients undergoing aortic valve surgery with an ejection fraction of more than 30% were included in this prospective audit. Induction of anesthesia was done using fentanyl, 2 to 4 mug/kg, propofol, 1 to 2 mg/kg, and endotracheal intubation facilitated by rocuronium; anesthesia was maintained using sevoflurane titrated according to bispectral index (BIS [BIS target: 50]). Perioperative analgesia was provided by high thoracic epidural analgesia (TEA group, bupivacaine 0.125%, 6 to 14 mL/h) or fentanyl, up to 10 microg/kg, followed by patient-controlled analgesia with morphine (OPIOID group). MEASUREMENTS AND MAIN RESULTS: Success of extubation within 30 minutes after surgery was recorded. Hemodynamic data during surgery were compared by using an analysis of variance test; p < 0.05 was considered as showing a significant difference. Data presented as median (25th-75th percentile). In the TEA group, patients underwent simple aortic valve replacement (N = 21) or combined aortic valve surgery (N = 14), with additional coronary artery bypass grafting (N = 10) and replacement of the ascending aorta (Bentall, N = 4). In the OPIOID group, patients underwent simple aortic valve replacement (N = 5) or combined aortic valve surgery (N = 5), with additional aortocoronary bypass grafting (N = 2), replacement of the ascending aorta (Bentall, N = 2), and reconstruction of the mitral valve (N = 1). All 45 patients were extubated within 15 minutes after surgery. There was no need for reintubation; pain scores were lower in the TEA group than in the OPIOID group immediately after surgery and at 6 hours, 24 hours, and 48 hours after surgery. For the TEA group and OPIOID group, the pain scores were 0 (0-2), 0 (0-2), 0 (0-1.5), and 0 (0-0) and 5 (4-5.75), 4 (3-4.5), 4 (3.25-4), and 1 (0-2.5), respectively. During and up to 6 hours after surgery, there was no significant hemodynamic difference between the TEA and OPIOID groups. Eighteen of 45 patients needed temporary pacemaker activation. There were no epidural hematoma or neurologic complications related to TEA. CONCLUSION: Immediate extubation is feasible after aortic valve surgery using either high thoracic epidural analgesia or opioid-based analgesia; both techniques maintain hemodynamic stability throughout surgery. TEA provides superior pain control.