Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20¿95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local¿+¿regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required.

Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study

OBJECTIVES To evaluate the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. DESIGN Prospective cohort study using the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP). SETTING Inpatient and outpatient procedures in 374 hospitals of all types across the United States, 2005-12. PARTICIPANTS 2,305,380 adults who underwent surgical procedures. MAIN OUTCOME MEASURES Arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery. RESULTS Among all surgical procedures, patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratios were 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. The adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis, compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had a twofold increased odds of thrombosis. CONCLUSIONS Preoperative sepsis represents an important independent risk factor for both arterial and venous thromboses. The risk of thrombosis increases with the severity of the inflammatory response and is higher in both emergent and elective surgical procedures. Suspicion of thrombosis should be higher in patients with sepsis who undergo surgery.

PLACENTAL GLUCOSE TRANSPORTER (GLUT)-1 REGULATION IN PREECLAMPSIA

PLACENTAL GLUCOSE TRANSPORTER (GLUT)-1 REGULATION IN PREECLAMPSIA Camilla Marini a,b, Benjamin P. Lüscher a,b, Marianne J€orger-Messerli a,b, Ruth Sager a,b, Xiao Huang c, Jürg Gertsch c, Matthias A. Hediger c, Christiane Albrecht c, Marc U. Baumann a,c, Daniel V. Surbek a,c a Department of Obstetrics and Gynecology, University Hospital of Bern, Bern, Switzerland, Switzerland; b Department of Clinical Research, University of Bern, Bern, Switzerland, Switzerland; c Institute for Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland, Switzerland Objectives: Glucose is a primary energy source for the fetus. The absence of significant gluconeogenesis in the fetus means that the fetal up-take of this vital nutrient is dependent on maternal supply and subsequent transplacental transport. Altered expression and/or function of placental transporters may affect the intrauterine environment and could compromise fetal and mother well-being. We speculated that pre-eclampsia (PE) impairs the placental glucose transport system. Methods: Placentae were obtained after elective caesarean sections following normal pregnancies and pre-eclamptic pregnancies. Syncytial basal membrane (BM) and apical microvillus membrane (MVM) fractions were prepared using differential ultra-centrifugation and magnesium precipitation. Protein expression was assessed by western blot analysis. mRNA levels in whole villous tissue lysate were quantified by real-time PCR. To assess glucose transport activity a radiolabeled substrate up-take assay and a transepithelial transport model using primary cytotrophoblasts were established. Results: GLUT1 mRNA expression was not changed in PE when compared to control, whereas protein expression was significantly down-regulated. Glucose up-take into syncytial microvesicles was reduced in PE compared to control. In a transepithelial transport model, phloretinmediated inhibition of GLUT1 at the apical side of primary cytotrophoblasts showed a 44% of reduction of transepithelial glucose transport at IC50. Conclusions: GLUT1 is down-regulated on protein and functional level in PE compared to control. Altering glucose transport activity by inhibition of apical GLUT-1 indicates that transplacental glucose transport might be regulated on the apical side of the syncytiotrophoblast. These results might help to understand better the regulation of GLUT1 transporter and maybe in future to develop preventive strategies to modulate the fetal programming and thereby reduce the incidence of disease for both the mother and her child later in life.

Placental Glucose Transporter (GLUT1) Expression in Pre-Eclampsia

Placental Glucose Transporter (GLUT1) Expression in Pre- Eclampsia. INTRODUCTION: Glucose is the most important substrate for fetal growth. Indeed, there is no significant de novo glucose synthesis in the fetus and the fetal up-take of glucose rely on maternal supply and transplacental transport. Therefore, a defective placental transporter system may affect the intrauterine environment compromising fetal as well as mother well-being. On this line, we speculated that the placental glucose transport system could be impaired in pre-eclampsia (PE). METHODS: Placentae were obtained after elective caesarean sections following normal pregnancies and pre-eclamptic pregnancies. Syncytial basal membrane (BM) and apical microvillus membrane (MVM) fractions were prepared using differential ultra-centrifugation and magnesium precipitation. Protein expression was assessed by western blot. mRNA levels were quantified by quantitative real-time PCR. A radiolabeled substrate up-take assay was established to assess glucose transport activity. FACS analysis was performed to check the shape of MVM. Statistical analysis was performed using one way ANOVA test. RESULTS: GLUT1 protein levels were down-regulated (70%; P<0.01) in pre-eclamptic placentae when compared to control placentae. This data is in line with the reduced glucose up-take in MVM prepared from preeclamptic placentae. Of note, the mRNA levels of GLUT1 did not change between placentae affected by PE and normal placentae, suggesting that the levels of GLUT1 are post-transcriptionally regulated. FACS analysis on MVM vesicles from both normal placentae and pre-eclamptic placentae showed equal heterogeneity in the complexes formed. This excluded the possibility that the altered glucose up-take observed in pre-eclamptic MVM was caused by a different shape of these vesicles. CONCLUSIONS: Protein and functional studies of GLUT1 in MVM suggest that in pre-eclampsia the glucose transport between mother and fetus might be defective. To further investigate this important biological aspect we will increase the number of samples obtained from patients and use primary cells to study trans epithelial transport system in vitro.

Displaced supracondylar humeral fractures: influence of delay of surgery on the incidence of open reduction, complications and outcome.

BACKGROUND Closed reduction and pinning is the accepted treatment choice for dislocated supracondylar humeral fractures in children (SCHF). Rates of open reduction, complications and outcome are reported to be dependent on delay of surgery. We investigated whether delay of surgery had influence on the incidence of open reduction, complications and outcome of surgical treatment of SCHFs in the authors' institution. METHODS Three hundred and forty-one children with 343 supracondylar humeral fractures (Gartland II: 144; Gartland III: 199) who underwent surgery between 2000 and 2009 were retrospectively analysed. The group consisted of 194 males and 149 females. The average age was 6.3 years. Mean follow-up was 6.2 months. Time interval between trauma and surgical intervention was determined using our institutional database. Clinical and radiographical data were collected for each group. Influence of delay of treatment on rates of open reduction, complications and outcome was calculated using logistic regression analysis. Furthermore, patients were grouped into 4 groups of delay (<6 h, n = 166; 6-12 h, n = 95; 12-24 h, n = 68; >24 h, n = 14) and the aforementioned variables were compared among these groups. RESULTS The incidence of open procedures in 343 supracondylar humeral fractures was 2.6 %. Complication rates were similar to the literature (10.8 %) primarily consisting of transient neurological impairments (9.0 %) which all were fully reversible by conservative treatment. Poor outcome was seen in 1.7 % of the patients. Delay of surgical treatment had no influence on rates of open surgery (p = 0.662), complications (p = 0.365) or poor outcome (p = 0.942). CONCLUSIONS In this retrospective study delay of treatment of SCHF did not have significant influence on the incidence of open reduction, complications, and outcome. Therefore, in SCHF with sufficient blood perfusion and nerve function, elective treatment is reasonable to avoid surgical interventions in the middle of the night which are stressful and wearing both for patients and for surgeons. LEVEL OF EVIDENCE III (retrospective comparative study).

Blind intubation of anaesthetised children with supraglottic airway devices AmbuAura-i and Air-Q cannot be recommended: A randomised controlled trial.

BACKGROUND Paediatric supraglottic airway devices AmbuAura-i and Air-Q were designed as conduits for tracheal intubation. Although fibreoptic-guided intubation has proved successful, blind intubation as a rescue technique has never been evaluated. OBJECTIVE Evaluation of blind intubation through AmbuAura-i and Air-Q. On the basis of fibreoptic view data, we hypothesised that the success rate with the AmbuAura-i would be higher than with the Air-Q. DESIGN A prospective, randomised controlled trial with institutional review board (IRB) approval and written informed consent. SETTING University Childrens' Hospital; September 2012 to July 2014. PATIENTS Eighty children, American Society of Anesthesiologists (ASA) class I to III, weight 5 to 50 kg. INTERVENTIONS Tracheal intubation was performed through the randomised device with the tip of a fibrescope placed inside and proximal to the tip of the tracheal tube. This permitted sight of tube advancement, but without fibreoptic guidance (visualised blind intubation). MAIN OUTCOME MEASURES Primary outcome was successfully visualised blind intubation; secondary outcomes included supraglottic airway device success, insertion times, airway leak pressure, fibreoptic view and adverse events. RESULTS Personal data did not differ between groups. In contrast to our hypothesis, blind intubation was possible in 15% with the Air-Q and in 3% with the AmbuAura-i [95% confidence interval (95% CI) 6 to 31 vs. 0 to 13%; P = 0.057]. First attempt supraglottic airway device insertion success rates were 95% (Air-Q) and 100% (AmbuAura-i; 95% CI 83 to 99 vs. 91 to 100; P = 0.49). Median leak pressures were 18 cmH2O (Air-Q) and 17 cmH2O [AmbuAura-i; interquartile range (IQR) 14 to 18 vs. 14 to 19 cmH2O; P = 0.66]. Air-Q insertion was slower (27 vs. 19 s, P < 0.001). There was no difference in fibreoptic view, or adverse events (P > 0.05). In one child (Air-Q size 1.5, tube size 3.5), the tube dislocated during device removal. CONCLUSION Ventilation with both devices is reliable, but success of blind intubation is unacceptably low and cannot be recommended for elective or rescue purposes. If intubation through a paediatric supraglottic airway device is desired, we suggest that fibreoptic guidance is used. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01692522.

Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer.

PURPOSE Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy. MATERIAL AND METHODS Thirty-nine patients with cervical carcinoma FIGO stage IB2 - IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with (18)FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15-18 Gy in three fractions (single fraction: 4-6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0). RESULTS Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness. CONCLUSION Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low.

Changes in Left Ventricular Torsion Early Postoperatively After Aortic Valve Replacement and at Long-Term Follow-up.

OBJECTIVE In patients with aortic stenosis, left ventricular systolic torsion (pT) is increased to overcome excessive afterload. This study assessed left ventricular torsion before and immediately after surgical valve replacement and tested the instant effect of fluid loading. DESIGN Prospective, clinical single-center study. SETTING Intensive care unit of a university hospital. PARTICIPANTS 12 patients undergoing elective aortic valve replacement for aortic stenosis. INTERVENTIONS Echocardiography was performed on the day before surgery, within 18 hours after surgery including a fluid challenge, and after 2.5 years. MEASUREMENTS AND MAIN RESULTS pT decreased early postoperatively by 21.2% (23.4° ± 5.6° to 18.4° ± 6.9°; p = 0.012) and reached preoperative values at 2.5 years follow-up (24 ± 7). Peak diastolic untwisting velocity occurred later early postoperatively (13% ± 8% to 21% ± 9.4%; p = 0.019) and returned toward preoperative values at follow-up (10.2 ± 4.7°). The fluid challenge increased central venous pressure (8 ± 4 mmHg to 11 ± 4 mmHg; p = 0.003) and reduced peak systolic torsion velocity (138.7 ± 37.6/s to 121.3 ± 32/s; p = 0.032). pT decreased in 3 and increased in 8 patients after fluid loading. Patients whose pT increased had higher early mitral inflow velocity postoperatively (p = 0.04) than those with decreasing pT. Patients with reduced pT after fluid loading received more fluids (p = 0.04) and had a higher positive fluid balance during the intensive care unit stay (p = 0.03). Torsion after fluid loading correlated with total fluid input (p = 0.001) and cumulative fluid balance (p = 0.002). CONCLUSIONS pT decreased early after aortic valve replacement but remained elevated despite elimination of aortic stenosis. After 2.5 years, torsion had returned to preoperative levels.

Clinical evaluation of ketamine and lidocaine intravenous infusions to reduce isoflurane requirements in horses under general anaesthesia

OBJECTIVE To compare isoflurane alone or in combination with systemic ketamine and lidocaine for general anaesthesia in horses. STUDY DESIGN Prospective, randomized, blinded clinical trial. ANIMALS Forty horses (ASA I-III) undergoing elective surgery. METHODS Horses were assigned to receive isoflurane anaesthesia alone (ISO) or with ketamine and lidocaine (LKI). After receiving romifidine, diazepam, and ketamine, the isoflurane end-tidal concentration was set at 1.3% and subsequently adjusted by the anaesthetist (unaware of treatments) to maintain a light plane of surgical anaesthesia. Animals in the LKI group received lidocaine (1.5 mg kg(-1) over 10 minutes, followed by 40 microg kg(-1) minute(-1)) and ketamine (60 microg kg(-1) minute(-1)), both reduced to 65% of the initial dose after 50 minutes, and stopped 15 minutes before the end of anaesthesia. Standard clinical cardiovascular and respiratory parameters were monitored. Recovery quality was scored from one (very good) to five (very poor). Differences between ISO and LKI groups were analysed with a two-sample t-test for parametric data or a Fischer's exact test for proportions (p < 0.05 for significance). Results are mean +/- SD. RESULTS Heart rate was lower (p = 0.001) for LKI (29 +/- 4) than for ISO (34 +/- 6). End-tidal concentrations of isoflurane (ISO: 1.57% +/- 0.22; LKI: 0.97% +/- 0.33), the number of horses requiring thiopental (ISO: 10; LKI: 2) or dobutamine (ISO:8; LKI:3), and dobutamine infusion rates (ISO:0.26 +/- 0.09; LKI:0.18 +/- 0.06 microg kg(-1) minute(-1)) were significantly lower in LKI compared to the ISO group (p < 0.001). No other significant differences were found, including recovery scores. CONCLUSIONS AND CLINICAL RELEVANCE These results support the use of lidocaine and ketamine to improve anaesthetic and cardiovascular stability during isoflurane anaesthesia lasting up to 2 hours in mechanically ventilated horses, with comparable quality of recovery.

Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

Single-center experience in the management of spontaneous isolated abdominal aortic dissection

OBJECTIVE This study aims to report the management of patients with spontaneous isolated dissection of the abdominal aorta (sIAAD). METHODS A cohort of 18 consecutive patients (12 male, mean age 58 years) with sIAAD was treated between 1990 and 2009. Dissection was asymptomatic in ten and symptomatic in eight patients. Retrospective data analysis from patient charts was performed. Follow-up included clinical examination, ultrasound, and/or CT-angiography. Mean follow-up was 54 months (range 1-211). RESULTS In total, eight out of 18 received invasive treatment. All asymptomatic patients initially underwent conservative treatment and surveillance. Spontaneous false lumen thrombosis occurred in four (40 %), and three patients showed relevant aneurysmatic progression and underwent elective invasive treatment (open n = 2, endovascular n = 1), representing a crossover rate of 30 %. Late mortality was 20 % (n = 2) in this group. In symptomatic patients, five underwent urgent treatment due to persistent abdominal or back pain (n = 4) or contained rupture (n = 1); one was treated for claudication. The remaining two patients presented with irreversible spinal cord ischemia and were treated conservatively. Three patients were treated by open surgery and three by endovascular interventions (two stentgrafts, one Palmaz XXL stent). Early and late morbidity and mortality was 0 % in this group. There were no reinterventions CONCLUSION: The majority of patients with sIADD require invasive treatment, with EVAR being the preferable treatment option today. In asymptomatic IADD, primary surveillance is justifiable, but close surveillance due to expansion is necessary.

Impact of case-relevant and case-irrelevant communication within the surgical team on surgical-site infection

BACKGROUND Surgical-site infections (SSIs) are the most common complications after surgery. An influence from talking and distractions during surgery on patient outcomes has been suggested, but there is limited evidence. The aim of this prospective observational study was to assess the relationship between intraoperative communication within the surgical team and SSI, and between intraoperative distractions and SSI. METHODS This prospective observational study included patients undergoing elective, open abdominal procedures. For each procedure, intraoperative case-relevant and case-irrelevant communication, and intraoperative distractions were observed continuously on site. The influence of communication and distractions on SSI after surgery was assessed using logistic regressions, adjusting for risk factors. RESULTS A total of 167 observed procedures were analysed; their mean(s.d.) duration was 4·6(2·1) h. A total of 24 SSIs (14·4 per cent) were diagnosed. Case-relevant communication during the procedure was independently associated with a reduced incidence of organ/space SSI (propensity score-adjusted odds ratio 0·86, 95 per cent c.i. 0·77 to 0·97; P = 0·014). Case-irrelevant communication during the closing phase of the procedure was independently associated with increased incidence of incisional SSI (propensity score-adjusted odds ratio 1·29, 1·08 to 1·55; P = 0·006). Distractions had no association with SSI. CONCLUSION More case-relevant communication was associated with fewer organ/space SSIs, and more case-irrelevant communication during wound closure was associated with incisional SSI.

Twenty years' experience with the Swiss data registry for assisted reproductive medicine: outcomes, key trends and recommendations for improved practice.

QUESTIONS UNDER STUDY The impact of assisted reproductive technology (ART) on Swiss demography was quantified. From 1993 to 2012 the number of deliveries, including multiples, generated by ART was compared with overall delivery numbers. Swiss experts in ART collaborated in a consensus to increase successful outcomes, to reduce the incidence of complications of ART and to validate recommendations through statistical review of available data. METHODS Data generated between 1993 and 2012 and published by the Federal Office of Statistics (BfS) were compared with the Swiss database on ART (FIVNAT-CH) as organised by the Swiss Society of Reproductive Medicine (SGRM). From these analyses a panel of Swiss experts in ART extracted recommendations to improve current practice, to prevent complications related to ART and to recommend changes in current Swiss legislation dealing with ART. RESULTS Since 1993 the age of women giving birth rose together with the number of women asking for ART. This demographic trend was reflected in a rise in the number of deliveries generated by ART (in 2012: 2.2%) and the proportion of multiple births (in 2012: 17.6%). The outcome of ART was most negatively influenced by the age of the treated patient. The number of retrieved oocytes decisively impacted the likelihood of delivery, the risk of multiple births and the incidence of ovarian hyperstimulation syndrome. CONCLUSIONS Optimal ovarian stimulation should be designed for the retrieval of 10 to 15 oocytes per treatment. Swiss legislation should enable and stimulate a policy of elective single embryo transfer to avoid multiple births.

Anaesthetic induction with etomidate in cardiac surgery: A randomised controlled trial.

BACKGROUND Etomidate is perceived as preserving haemodynamic stability during induction of anaesthesia. It is also associated with adrenocortical dysfunction. The risk/benefit relationship is controversial. OBJECTIVES We tested the hypotheses that single-dose etomidate increases cumulative vasopressor requirement, time to extubation and length of stay in the ICU. DESIGN Double-blind randomised controlled trial. SETTING Bern University Hospital, Switzerland, from November 2006 to December 2009. PATIENTS There were 90 patients undergoing coronary artery bypass grafts (CABG) and 40 patients undergoing mitral valve surgery (MVS). Reasons for noninclusion were known adrenocortical insufficiency, use of etomidate or propofol within 1 week preoperatively, use of glucocorticoids within 6 months preoperatively, severe renal or liver dysfunction, or carotid stenosis. INTERVENTIONS CABG patients were allocated randomly to receive either etomidate 0.15 mg kg with placebo, propofol 1.5 mg kg with placebo or etomidate 0.15 mg kg with hydrocortisone (n = 30 in each arm). Risk stratification (low vs. high) was achieved by block randomisation. MVS patients received either etomidate 0.15 mg kg or propofol 1.5 mg kg (n = 20 in each arm). MAIN OUTCOME MEASURES Cumulative vasopressor requirements, incidence of adrenocortical insufficiency, length of time to extubation and length of stay in ICU. RESULTS Cumulative vasopressor requirements 24 h after induction did not differ between treatments in patients who underwent CABG, whereas more noradrenaline was used in MVS patients following propofol induction (absolute mean difference 5.86 μg kg over 24 h P = 0.047). The incidence of relative adrenocortical insufficiency was higher after etomidate alone than propofol (CABG 83 vs. 37%, P < 0.001; MVS: 95 vs. 35%, P < 0.001). The time to extubation, length of stay in ICU and 30-day mortality did not differ among treatments. Within low and high-risk subgroups, no differences in vasopressor use or outcomes were found. CONCLUSION In elective cardiac surgery, laboratory indicators of etomidate-induced adrenal insufficiency do not translate into increased vasopressor requirement or inferior early outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT 00415701.

Exercise and Mood: Exploring the Role of Exercise in Regulating Stress Reactivity in Bipolar Disorder

Bipolar Disorder (BD) is a recurrent and debilitating psychological disorder characterized by a chronic dysregulation of mood with fluctuations between extremely low (e.g., depression) and extremely elevated mood states (e.g., mania), and ranks as the 6th leading cause of disability in the world. Although research has consistently shown that exercise may have antidepressant and stress-attenuating benefits in other psychiatric illnesses (e.g., depression, anxiety), these benefits have not been directly investigated for BD. The current study represents the first known investigation to examine this relationship. Single-participant designs, with crossover and interaction treatment components (i.e., A/B/A/B/A, A/C/A/C/A, A/B/A/C/A, or A/C/A/B/A) were utilized to investigate the impact of participation in a prescribed regimen of exercise (EP) versus standard behavioral activation (SBA; i.e., non-exercise activity) has on stress perception and reactivity, and mood stability in a sample of individuals with BD. Individuals completed four total weeks of treatment, and psychophysiological measures of reactivity were recorded during a laboratory stress task (i.e., backward counting task) prior to and following each two-week intervention phase. No appreciable differences were found between levels of exercise participation between treatment groups. Interestingly, symptoms of depressed mood (BDI-II scores) decreased at similar rates following 4 weeks of treatment for all participants. BDI-II decreases were found to be most correlated with elective exercise participation, although this relationship was not significant. Regarding stress reactivity, elective participation in mild to moderate intensity exercise was found to reduce an individual’s perception of stress reactivity to an acute stressor, while participation in a prescribed program of exercise was more effective in reducing physiological response to the same task. Utilizing multiple forms of behavioral activation simultaneously was found to be most effective in decreasing perception of stress reactivity, and may also result in a positive change in the use of adaptive versus maladaptive coping strategies. Participation in a 4-week program of exercise appeared to provide the most benefit, consistent with exercise habituation theories. Overall, current findings provide preliminary support for the prophylactic benefits of including a prescribed and monitored program of exercise as an adjunct treatment for individuals with BD. Larger scale research is needed to more clearly determine the impact of exercise on stress reactivity and mood episode relapse in individuals with BD.