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Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, pegorgotein, and 17β-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, pegorgotein, and 17β-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.

Background: Postoperative delirium can result in increased postoperative morbidity and mortality, major demand for postoperative care and higher hospital costs. Hypnotics serve to induce and maintain anaesthesia and to abolish patients' consciousness. Their persisting clinical action can delay postoperative cognitive recovery and favour postoperative delirium. Some evidence suggests that these unwanted effects vary according to each hypnotic's specific pharmacodynamic and pharmacokinetic characteristics and its interaction with the individual patient.We designed this study to evaluate postoperative delirium rate after general anaesthesia with various hypnotics in patients undergoing surgical procedures other than cardiac or brain surgery. We also aimed to test whether delayed postoperative cognitive recovery increases the risk of postoperative delirium., Methods/design: After local ethics committee approval, enrolled patients will be randomly assigned to one of three treatment groups. In all patients anaesthesia will be induced with propofol and fentanyl, and maintained with the anaesthetics desflurane, or sevoflurane, or propofol and the analgesic opioid fentanyl.The onset of postoperative delirium will be monitored with the Nursing Delirium Scale every three hours up to 72 hours post anaesthesia. Cognitive function will be evaluated with two cognitive test batteries (the Short Memory Orientation Memory Concentration Test and the Rancho Los Amigos Scale) preoperatively, at baseline, and postoperatively at 20, 40 and 60 min after extubation.Statistical analysis will investigate differences in the hypnotics used to maintain anaesthesia and the odds ratios for postoperative delirium, the relation of early postoperative cognitive recovery and postoperative delirium rate. A subgroup analysis will be used to categorize patients according to demographic variables relevant to the risk of postoperative delirium (age, sex, body weight) and to the preoperative score index for delirium., Discussion: The results of this comparative anaesthesiological trial should whether each the three hypnotics tested is related to a significantly different postoperative delirium rate. This information could ultimately allow us to select the most appropriate hypnotic to maintain anaesthesia for specific subgroups of patients and especially for those at high risk of postoperative delirium. REGISTERED AT TRIAL.GOV NUMBER: ClinicalTrials.gov: NCT00507195.

All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction-negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction-negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.

The aim of this prospective study was to determine the prevalence of pre-operative atrial fibrillation and the incidence of postoperative atrial fibrillation in patients undergoing elective or emergency intracranial neurosurgical procedures and the relation to survival and neurological outcome at 6-months follow-up compared to patients with sinus rhythm. A total of 2020 patients were enrolled; 1540 patients underwent elective procedures and 480 underwent emergency procedures. Prevalence of pre-operative atrial fibrillation was 3.7% in elective and 7.2% in emergency procedures (p = 0.0012). In patients undergoing elective cerebral procedures with pre-operative atrial fibrillation, compared to patients with sinus rhythm, 6-month neurological outcome and survival rate are similar. In patients undergoing emergency neurosurgical cerebral procedures, the presence of pre-operative atrial fibrillation is related to an increased risk of poor neurological outcome but with similar survival rate.

Background: Intensive insulin therapy to maintain blood glucose at or below 6.11 mM reduces morbidity and mortality after cardiac surgery and morbidity in medical intensive care unit (ICU) patients. The authors investigated the clinical safety and outcome effects of intensive insulin therapy compared to conventional insulin therapy in patients receiving postoperative intensive care after neurosurgical procedures., Methods: In this prospective randomized controlled trial, 483 patients undergoing elective or emergency brain surgery were prospectively and randomly assigned either to intensive insulin therapy (241 patients), receiving insulin titrated to maintain blood glucose levels within the range of 4.44-6.11 mM, or to conventional insulin therapy (242 patients), receiving insulin to maintain blood glucose levels below 11.94 mM. Primary endpoint was incidence of hypoglycemia (defined as blood glucose < 2.78 mM). Efficacy measures included the length of ICU stay, infection rate, and 6 months follow-up Glasgow outcome scale score and overall survival., Results: Hypoglycemia episodes were more frequent in patients receiving intensive insulin therapy, median (min-max): 8 (0-23) versus 3 (0-4); P < 0.0001. The length of stay in the ICU was shorter (6 vs. 8 days; P = 0.0001), and the infection rate was lower (25.7% vs. 39.3%; P = 0.0018). Glasgow outcome scale score and overall survival at 6 months were similar in the two groups., Conclusions: Intensive insulin therapy in patients admitted to a postoperative neurosurgical ICU after brain surgery is associated with iatrogenic hypoglycemia, but it can also reduce the infection rate and shorten the ICU stay.

Introduction: To investigate the risks and possible benefits of routine versus intensive insulin therapy, assessed by the frequency of hypoglycemic events defined as a glucose concentration less than 80 mg/dl (<4.44 mmol/l) in patients admitted to the intensive care unit (ICU) after severe traumatic brain injury (TBI)., Methods and Results: Ninety-seven patients admitted after severe TBI, were enrolled and randomly assigned to two groups of target glycemia. Insulin was infused at conventional rates when blood glucose levels exceeded 220 mg/dl (12.22 mmol/l) or at intensive rates, to maintain glycemia at 80-120 mg/dl (4.44-6.66 mmol/l). The following primary and outcome variables were measured during follow-up: hypoglycemic episodes, duration of ICU stay, infection rate, and 6-month mortality and neurologic outcome measured using the Glasgow Outcome Scale (GOS). Episodes of hypoglycemia (defined as blood glucose <80 mg/dl or 4.44 mmol/l) were significantly higher in patients receiving intensive insulin therapy: median (min-max) conventional insulin therapy 7 (range 0-11) vs. intensive insulin therapy 15 (range 6-33); P<0.0001. Duration of ICU stay was shorter in patients receiving intensive insulin therapy (7.3 vs. 10.0 days; P < 0.05); while infection rates during ICU stay (25.0% vs. 38.8%, P = 0.15), and GOS scores and mortality at 6 months were similar in the two groups., Conclusions: Intensive insulin therapy significantly increases the risk of hypoglycemic episodes. Even though patients receiving intensive insulin therapy have shorter ICU stays and infection rates similar to those receiving conventional insulin therapy, both groups have similar follow-up mortality and neurologic outcome. Hence if intensive insulin therapy is to be used, great effort must be taken to avoid hypoglycemia.

The family of semi-crystalline, aromatic, high-temperature thermoplastics known as poly(ether-ketone)s are insoluble in conventional organic solvents, but undergo completely general and quantitatively reversible reactions with alkanedithiols in strong acid media, to give soluble poly(dithioacetal)s, which are readily characterisable by GPC and light scattering techniques.

Background and Objective: This study was designed to evaluate early postoperative cognitive recovery after total intravenous anaesthesia with remifentanil-propofol or sufentanil-propofol in patients undergoing craniotomy for supratentorial expanding lesions., Methods: Sixty patients were consecutively enrolled, and randomly assigned to one of two study groups: remifentanil-propofol or sufentanil-propofol anaesthesia. To evaluate cognitive function the Short Orientation Memory Concentration Test (SOMCT) and Rancho Los Amigos Scale (RLAS) were administered to all patients in a double-blind procedure before surgery at 15, 45 min and 3 h after extubation., Results: Mean extubation time was similar in the two groups (13 +/- 5 min vs. 19 +/- 6 min). A significantly larger number of patients in the remifentanil-propofol group than in the sufentanil-propofol group required antihypertensive medication postoperatively to maintain mean arterial pressure within 20% of baseline (18/30 vs. 4/29; P = 0.0004). Intergroup analysis showed no differences in baseline SOMCT scores (28 +/- 1 vs. 28 +/- 1) whereas mean SOMCT scores at 15, 45 min and 3 h after extubation were significantly higher in the remifentanil-propofol group (30 patients) than in the sufentanil-propofol group (29 patients) (22 +/- 3 vs. 16 +/- 3; P < 0.0001 and 27 +/- 1 vs. 22 +/- 3; P < 0.0001; 28 +/- 1 vs. 26 +/- 2; P = 0.0126)., Conclusions: In conclusion, propofol-remifentanil and propofol-sufentanil are both suitable for fast-track neuroanaesthesia and provide similar intraoperative haemodynamics, awakening and extubation times. Despite a higher risk of treatable postoperative hypertension propofol-remifentanil allows earlier cognitive recovery.

Purpose: Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer., Patients and Methods: Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks., Results: Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months., Conclusion: The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.