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Acute kidney injury (AKI) is common after cardiac surgery. We quantified the mortality and costs of varying degrees of AKI using a population-based cohort in Alberta, Canada.A cohort of patients undergoing cardiac surgery from 2004 to 2009 was assembled from linked Alberta administrative databases. AKI was classified by Kidney Disease Improving Global Outcomes stages of severity. Our outcomes were in-hospital mortality, length of stay, and costs; among survivors, we also examined mortality and costs at 365 days. Estimates were adjusted for demographic characteristics, comorbidities, and other covariates.Ten thousand one hundred seventy participants were included, of whom 9771 patients were discharged to community. Overall in-hospital mortality, costs, and length of stay were 4%, 7 days, and Can $34,000, respectively. Postcardiac surgery, AKI occurred in 25%. Compared with those without AKI, AKI was independently associated with increased in-hospital mortality across severity categories, with the highest risk (adjusted odds ratio, 37.1; 95% confidence interval, 26.3-52.1; P .001) in patients who required acute dialysis. AKI severity was associated with increased hospital days and costs, with costs ranging from 1.21 for stage 1 AKI (95% confidence interval, 1.17-1.23) to 2.74 for acute dialysis (95% confidence interval, 2.49-3.00) (P .001) times higher than in patients without AKI, after covariate adjustment. Postdischarge to 365 days, patients with AKI continued to experience increased costs up to 1.35-fold, and patients who required dialysis acutely continued to experience a 2.86-fold increased mortality.AKI remains an important indicator of mortality and health care costs postcardiac surgery.

OBJECTIVES Despite society guideline recommendations, intraoperative high-frequency ultrasound (HFUS) and transit-time flow measurement (TTFM) use in coronary artery bypass grafting (CABG) has not been widely adopted worldwide. This retrospective review of the REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study assesses the impact of protocolled high-frequency ultrasound/TTFM use in specific technical circumstances of CABG. METHODS Three REQUEST study sub-analyses were examined: (i) For off-pump (OPCAB) versus on-pump (ONCAB) procedures: strategy changes from preoperative plans for the aorta, conduits, coronary targets and graft revisions; and for all REQUEST patients, revision rates in: (ii) arterial versus venous grafts; and (iii) grafts to different cardiac territories. RESULTS Four hundred and two (39.6%) of 1016 patients undergoing elective isolated CABG for multivessel disease underwent OPCAB procedures. Compared to ONCAB, OPCAB patients experienced more strategy changes regarding the aorta [14.7% vs 3.4%; odds ratios (OR) = 4.03; confidence interval (CI) = 2.32–7.20], less regarding conduits (0.2% vs 2.8%; OR = 0.09; CI = 0.01–0.56), with no differences in coronary target changes or graft revisions (4.1% vs 3.5%; OR = 1.19; CI = 0.78–1.81). In all REQUEST patients, revisions were more common for arterial versus venous grafts (4.7% vs 2.4%; OR = 2.05; CI = 1.29–3.37), and inferior versus anterior (5.1% vs 2.9%; OR = 1.77; CI = 1.08–2.89) and lateral (5.1% vs 2.8%; OR = 1.83; CI = 1.04–3.27) territory grafts. CONCLUSIONS High-frequency ultrasound/TTFM use differentially impacts strategy changes and graft revision rates in different technical circumstances of CABG. Notably, patients undergoing OPCAB experienced 4 times more changes related to the ascending aorta than ONCAB patients. These findings may indicate where intraoperative assessment is most usefully applied. Clinical trial registration number ClinicalTrials.gov: NCT02385344

Introduction Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. Methods The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0–2 vs. 3–6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. Results The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0–2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). Conclusion GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. Trial registration EudraCT-Nr. 2005–003201-81.

Background Intraoperative graft assessment with tools like Transit Time Flow Measurement (TTFM) is imperative for quality control in coronary surgery. We investigated the variation of TTFM parameters before and after protamine administration to identify new benchmark parameters for graft quality assessment. Methods The database of the REQUEST (“REgistry for QUality AssESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery”) study was retrospectively reviewed. A per graft analysis was performed. Only single grafts (i.e., no sequential nor composite grafts) where both pre- and post-protamine TTFM values were recorded with an acoustical coupling index > 30% were included. Grafts with incomplete data and mixed grafts (arterio-venous) were excluded. A second analysis was performed including single grafts only in the same MAP range pre- and post- protamine administration. Results After adjusting for MAP, we found a small increase in MGF (29 mL/min to 30 mL/min, p = 0.009) and decrease in PI (2.3 to 2.2, p Conclusion The small changes in TTFM parameters observed before and after protamine administration seem to be clinically irrelevant, despite being statistically significant in aggregate. Our data do not support a need to perform TTFM measurements both before and after protamine administration. A single TTFM measurement taken either before or after protamine may suffice to achieve reliable data on each graft’s performance. Depending on the specific clinical situation and intraoperative changes, more measurements may be informative. Trial registration Clinical Trials Number: NCT02385344, registered February 17th, 2015.

OBJECTIVES Factors such as more diffuse atherosclerosis, plaque instability and accelerated vascular calcification in patients with chronic and end-stage renal disease (ESRD) can potentially present intraoperative challenges in coronary artery bypass grafting (CABG) procedures. We evaluated whether patients with chronic and ESRD experienced more surgical strategy changes and/or graft revisions than patients with normal renal function when undergoing CABG procedures according to a protocol for intraoperative high-frequency ultrasound and transit-time flow measurement (TTFM). METHODS Outcomes of CABG for patients with chronic and ESRD and patients with normal renal function enrolled in the multicentre prospective REQUEST (REgistry for QUality assESsmenT with Ultrasound Imaging and TTFM in Cardiac Bypass Surgery) study were compared retrospectively. The primary end point was frequency of intraoperative surgical strategy changes. The secondary end point was post-protamine TTFM parameters. RESULTS There were 95 patients with chronic and ESRD and 921 patients with normal renal function. Patients with chronic and ESRD undergoing CABG according to a protocol for intraoperative high-frequency ultrasound and TTFM had a higher rate of strategy changes overall [33.7% vs 24.3%; odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.01–2.48; P = 0.047] and greater revisions per graft (7.0% vs 3.4%; odds ratio = 2.14; 95% CI = 1.17–3.71; P = 0.008) compared to patients with normal renal function. Final post-protamine graft TTFM parameters were comparable between cohorts. CONCLUSIONS Patients with chronic and ESRD undergoing CABG procedures with high-frequency ultrasound and TTFM experience more surgical strategy changes than patients with normal renal function while achieving comparable graft flow. Clinical trial registration number ClinicalTrials.gov NCT02385344

Intraoperative bypass graft evaluation for coronary artery bypass graft surgery has now been recommended in three consecutive European guidelines for myocardial revascularization in 2010, 2014, and 2018. The two main modalities consist of transit-time flow measurement which assesses function of grafts and epicardial ultrasound to assess the anatomy of the anastomosis. Functional and morphological assessment are generally considered complementary, although transit-time flow measurement is the most commonly used. Transit-time flow measurement alone may have ambiguous values in 5–15% of grafts and this can lead to unnecessary graft revision. The addition of epicardial ultrasound aids interpretation of intraoperative graft assessment by allowing visualization of the anastomosis and correction of technical errors that, intuitively, will lead to improved patient outcomes.

Summary Despite there being numerous studies of intraoperative graft flow assessment by transit-time flow measurement (TTFM) on outcomes after coronary artery bypass grafting (CABG), the adoption of contemporary TTFM is low. Therefore, on 31 January 2018, a systematic literature search was performed to identify articles that reported (i) the amount of grafts classified as abnormal or which were revised or (ii) an association between TTFM and outcomes during follow-up. Random-effects models were used to create pooled estimates with 95% confidence intervals (CI) of (i) the rate of graft revision per patient, (ii) the rate of graft revision per graft and (iii) the rate of graft revision among grafts deemed abnormal based on TTFM parameters. The search yielded 242 articles, and 66 original articles were included in the systematic review. Of those articles, 35 studies reported on abnormal grafts or graft revisions (8943 patients, 15 673 grafts) and were included in the meta-analysis. In 4.3% of patients (95% CI 3.3–5.7%, I2 = 73.9) a revision was required and 2.0% of grafts (95% CI 1.5–2.5%; I2 = 66.0) were revised. The pooled rate of graft revisions among abnormal grafts was 25.1% (95% CI 15.5–37.9%; I2 = 80.2). Studies reported sensitivity ranging from 0.250 to 0.457 and the specificity from 0.939 to 0.984. Reported negative predictive values ranged from 0.719 to 0.980 and reported positive predictive values ranged from 0.100 to 0.840. This systematic review and meta-analysis showed that TTFM could improve CABG procedures. However, due to heterogeneous data, drawing uniform conclusions appeared challenging. Future studies should focus on determining the optimal use of TTFM and assessing its diagnostic accuracy.

The "Achilles heel" of coronary artery bypass graft (CABG) surgery is graft patency. While long-term patency is determined by the type of conduit and the progression of graft and native vessel disease, short-term patency is affected by intra-operative technical issues. Transit-time flow measurements and epicardial ultrasound have been shown to accurately assess intra-operative graft patency. This review will examine the evidence to support the premise that intra-operative graft assessment is essential in determining graft patency and should be the standard of care when performing CABG surgery.

Objective To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts. Results This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema. Electronic supplementary material The online version of this article (10.1186/s13104-018-3168-1) contains supplementary material, which is available to authorized users.

Purpose of review The coronary artery bypass graft (CABG) operation is one of the few remaining operations/interventions on diseased arteries that are not routinely verified during or immediately after the procedure. This review answers the 'how', 'when' and 'why' of intraoperative CABG assessment. Recent findings More recent than new literature on this topic, is the increased interest in quality assurance of CABG. This is most likely due to reports in the last 5 years suggesting CABG superiority to percutaneous coronary intervention (PCI) for improved mid-term and long-term outcomes; for example, for patients with diabetes mellitus (Freedom Trial by Farkouh in 2012), and for patients with SYNTAX score ≥ 33 (SYNTAX Trial by Mohr in 2013). Possibly CABG is re-emerging from the era-of-better-and-better-stents and is now deemed worthy of improvement. Summary In order to fully compliment PCI, the operative major adverse cardiac event rate of CABG must rival that of PCI. In order to reduce technical errors, it is best practice to perform intra-operative assessment of bypasses, especially since we have the tools.

Objectives We evaluated the influence of transit-time flow measurement with epicardial and epiaortic high-frequency ultrasound in patients undergoing coronary artery bypass grafting procedure. Methods The Registry for Quality Assessment with Ultrasound Imaging and Transit-time Flow Measurement in Cardiac Bypass Surgery study is a multicenter, prospective study among 7 international centers performing coronary artery bypass grafting procedures. The primary end point was any change in the planned surgical procedure. Major secondary end points consisted of the rate and reason for surgical changes related to the aorta, in situ conduits, coronary targets, and completed grafts, and the rate of in-hospital mortality and major morbidity. Results Between April 2015 and December 2017, 1046 patients were enrolled. Of those, 1016 were included in the final analyses. Mean age was 65.9 years, 14.0% were women, and diabetes was present in 39.6%. Off-pump procedures were performed in 39.6% and bilateral internal thoracic arteries in 30.5%. The primary end point occurred in 25.2% of patients (n = 256) and in 77% (197 out of 256) this was based on transit-time flow measurement and/or high-frequency ultrasound. Surgical changes were related to the aorta in 9.9%, to in situ conduits in 2.7%, and the coronary targets in 22.6%. Graft revision occurred in 7.8%, including revisions of the proximal and/or distal anastomosis in 6.6%. In-hospital adverse event rates were 0.6% for mortality, 1.0% for cerebrovascular events, and 0.3% for myocardial infarction. Conclusions Surgical changes related to the aorta, conduits, coronary targets, and anastomosis were made in 25% of patients. This was associated with low operative mortality and low major morbidity. Transit-time flow measurement and high-frequency ultrasound may improve the quality, safety, and efficacy of coronary artery bypass grafting procedures and should be considered as a routine procedural aspect.

Coronary artery disease is the leading cause of morbidity and mortality even in the elderly population. Treatment opportunities in the elderly population are often underappreciated. Revascularization procedures (coronary artery bypass graft surgery and percutaneous coronary intervention) can be associated with important benefits in symptom control, quality of life, and long-term mortality, at an upfront cost of an increased risk of in-hospital mortality and morbidity. Risk models to assess periprocedural risk are useful. The best models would balance unique aspects of risk with the very real potential benefit of revascularization. Current models fall short in this regard. Frailty, a clinical syndrome of vulnerability, is present in 25%-50% of cardiac patients, and is associated with increased morbidity and mortality. The addition of frailty can improve the discrimination of risk models. Elderly patients commonly consider quality of life to have greater importance than mortality outcomes. Furthermore, hospital admission is associated with a reduction in mobilization, loss of muscle strength, and worsening frailty, and interferes with a fundamental value in the elderly: the maintenance of independence. Therefore, an understanding of frailty, quality of life, and other unique aspects of risk, as well as individual patient goals, can assist in further defining prognosis and refine decision-making in this important and vulnerable population.

In humans and other mammals, isocapnic hypoxia sustained for 20–60 min exhibits a biphasic ventilation pattern: initial increase followed by a significant ventilatory decline (“roll-off”) to a lesser intermediate plateau. During sustained hypoxia, the mechanical action and activity of the diaphragm have not been studied; thus we assessed diaphragm function in response to hypoxic breathing. Thirteen spontaneously breathing awake canines were exposed to moderate levels of sustained isocapnic hypoxia lasting 20–25 min (80 ± 2% pulse oximeter oxygen saturation). Breathing pattern and changes in muscle length and electromyogram (EMG) activity of the costal and crural diaphragm were continuously recorded. Mean tidal shortening and EMG activity of the costal and crural diaphragm exhibited an overall biphasic pattern, with initial brisk increase followed by a significant decline ( P < 0.01). Although costal and crural shortening did not differ significantly with sustained hypoxia, this equivalence in segmental shortening occurred despite distinct and differing EMG activities of the costal and crural segments. Specifically, initial hypoxia elicited a greater costal EMG activity compared with crural ( P < 0.05), whereas sustained hypoxia resulted in a lesser crural EMG decline/attenuation than costal ( P < 0.05). We conclude that sustained isocapnic hypoxia elicits a biphasic response in both ventilation and diaphragmatic function and there is clear differential activation and contribution of the two diaphragmatic segments. This different diaphragm segmental action is consistent with greater neural activation of costal diaphragm during initial hypoxia, then preferential sparing of crural activation as hypoxia is sustained. NEW & NOTEWORTHY In humans and other mammals, during isocapnic hypoxia sustained for 20–60 min ventilation exhibits a biphasic pattern: initial increase followed by significant ventilatory decline (“roll-off”). During sustained hypoxia, the function of the diaphragm is unknown. This study demonstrates that the diaphragm reveals a biphasic action during the time-dependent hypoxic “roll-off” in ventilation. These results also highlight that the two diaphragm segments, costal and crural, show differing, distinctive contributions to diaphragm function during sustained hypoxia.

Quality assurance (QA) in medicine is the practice of the prevention of errors and avoiding problems when delivering care in the form of medical therapy, both in terms of non-invasive and invasive procedures. It is rightly expected by patients. Up until the last 10 years, verification of intraoperative bypass graft patency was limited to a stable hemodynamic status, lack of electrocardiographic evidence of myocardial infarction and, if available, no new regional wall motion abnormalities on transesophageal echo. This perspective outlines two technologies for QA during coronary artery bypass graft (CABG) surgery: transit-time flow measurement (TTFM) for functional assessment of coronary grafts and anatomical evaluation with epicardial ultrasound (ECUS). TTFM is a seasoned technology, used since the late 1990s. ECUS is relatively new, used since 2012. TTFM alone, although useful for intraoperative bypass graft assessment, is not enough; 10-15% of graft values are ambiguous as to the efficacy of graft function. Therefore, although newer, ECUS is already being established as an indispensable tool for quality assessment in coronary surgery. The two modalities combined are vital for 'state of the art' intraoperative bypass graft assessment.

ObjectiveAt this consensus conference, we developed evidence-informed consensus statements and recommendations on the practice of off-pump coronary artery bypass graft (OPCAB) by systematically reviewing and performing meta-analysis of the randomized controlled trials (RCTs) comparing OPCAB and conventional coronary artery bypass (CCAB).MethodsAll RCTs of OPCAB versus CCAB through April 2013 were screened, and 102 relevant RCTs (19,101 patients) were included in a systematic review and meta-analysis (15 RCTs of 9551 high-risk patients; and 87 RCTs of 9550 low-risk patients) in accordance with the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Consensus statements for the risks and benefits of OPCAB surgery in mortality, morbidity, and resource use were developed based on best available evidence.ResultsCompared to CCAB, it is reasonable to perform OPCAB to reduce risks of stroke [class IIa, level of evidence (LOE) A], renal dysfunction/failure (class IIa, LOE A), blood transfusion (class I, LOE A), respiratory failure (class I, LOE A), atrial fibrillation (class I, LOE A), wound infection (class I, LOE A), ventilation time, and ICU and hospital length of stay (class I, LOE A). However, OPCAB may be associated with a reduced number of grafts performed (class I, LOE A) and with diminished graft patency (class IIa, LOE A, with increased coronary reintervention at 1 year and beyond (class IIa, LOE A), as well as increased mortality at a median follow-up of 5 years (class IIb, LOE A).ConclusionsOPCAB compared with CCAB may improve outcomes in the short-term (stroke, renal dysfunction, blood transfusion, respiratory failure, atrial fibrillation, wound infection, ventilation time, and length of stay). However, over the longer-term, OPCAB may be associated with reduced graft patency, and increased risk of cardiac re-intervention and death.

Rapid body mass loss (RBML) before competition was found to decrease hemoglobin mass (Hbmass ) in elite boxers. This study aimed to investigate the underlying mechanisms of this observation. Fourteen well-trained combat athletes who reduced body mass before competitions (weight loss group, WLG) and 14 combat athletes who did not practice RBML (control group, CON) were tested during an ordinary training period (t-1), 1-2 days before an official competition (after 5-7 days RBML in WLG, t-2), and after a post-competition period (t-3). In WLG, body mass (-5.5%, range: 2.9-6.8 kg) and Hbmass (-4.1%) were significantly (P

Surgical treatment for angina pectoris was first proposed in 1899. Decades of experimental surgery for coronary artery disease finally led to the introduction of coronary artery bypass grafting (CABG) in 1964. Now that we are approaching 50 years of CABG experience, it is appropriate to summarize the advancement of CABG into a procedure that is safe and efficient. This review provides a historical recapitulation of experimental surgery, the evolution of the surgical techniques and the utilization of CABG. Furthermore, data on contemporary clinical outcomes are discussed.

Purpose A large multicenter randomized trial (RCT) is needed to assess off-pump coronary artery bypass graft (CABG) patency when performed by skilled surgeons. This prospective multicenter randomized pilot study compares graft patency after on-pump and off-pump techniques and addresses the feasibility of such an RCT. Materials and methods Consecutive patients were prospectively recruited for ≥64-slice computed tomography angiography graft patency assessment 1 year after randomization to off-pump or on-pump CABG. Blinded assessment of graft patency was performed, and the results were categorized as normal, ≥50% stenosis, or occlusion. A multilevel model with random effects on the patient was used to account for correlation of results in patients with multiple grafts. Results A total of 157 patients (3 centers, 84 off-pump and 73 on-pump patients, 512 grafts, assessability rate 98.4%) were included. Patency index (% nonoccluded grafts) was 89% for the off-pump technique and 95% for the on-pump technique (P=0.09). Patency was similar for arterial and vein grafts (both 92%; P=0.88), as well as between target territories (89% to 94%; P=0.53). Conclusions In this pilot study, 1-year graft patency results after off-pump and on-pump surgery were similar. This feasibility trial demonstrates that a large multicenter RCT to compare CABG patency after on-pump with that after off-pump techniques is feasible and can be reliably undertaken using computed tomography angiography.

ObjectiveCoronary artery bypass graft (CABG) surgery with arterial conduits is considered optimal. A deterrent to bilateral internal thoracic artery (BITA) grafting is the risk of deep sternal wound infection (DSWI). We introduced infection prevention measures sequentially, attempting to reduce DSWIs. The aim was to determine (1) if the absence of DSWIs in the last 469 of 1001 consecutive operations was significant; (2) which measures explained the change; and (3) the impact of diabetes.MethodsThe measures included internal thoracic artery (ITA) skeletonization, no bone wax, wound irrigation, 1 observer per case, harmonic scalpel harvest of ITAs, vancomycin paste on sternal marrow, iodine-impregnated skin drapes, chlorhexidine-alcohol skin preparation, no BITA grafts in obese, diabetic women, more off-pump procedures, aseptic wound care, and marrow irrigation before sternal approximation.ResultsMean age was 65 ± 10.4 years, 78% were male, 34% had diabetes, and 34% were obese. The first 532 patients had 16 DSWIs (3%) and the subsequent 469 had none (P

BackgroundIt appears that the medical profile of patients undergoing coronary artery bypass graft (CABG) surgery has changed. The impact of this demographic shift on CABG outcomes, such as sternal ...

Current popular accounts of sexual morality for adolescents based simply on purity or self-determination cannot adequately anchor a Christian sexual ethic, although positions based on both notions hope to facilitate sexual health among young females. Here I critique both popular Christian purity movements and a popular feminist critique of these purity movements (based upon self-determination) and suggest the virtue of prudence as a corrective. Situated within the Catholic theological tradition, prudence (practical wisdom) acknowledges the process of human moral and sexual development and is robust enough to negotiate the concrete complexities of sexual activity and the social realities in which such activity takes place. Further, it honours an embodied sense of female sexual self-determination: females as moral agents directed towards sexual flourishing.

Dissection of the left main coronary artery during coronary artery bypass graft (CABG) surgery is a rare, potentially lethal complication, usually diagnosed at post-mortem. During the cross-clamp period of a 4-vessel coronary artery bypass graft procedure in a 74-year old hypertensive woman, retrograde dissection occurred in a diffusely diseased marginal artery when perfused with cardioplegic solution at a pressure of 140-150 mmHg through a vein graft. The dissection extended back to the left main artery, included the posterior proximal ascending aorta and then down the left anterior descending artery (LAD). Transoesophageal echocardiography (TOE) confirmed the left main dissection and showed anterior-septal-lateral akinesis in a previously normally functioning left ventricle (LV). The circumferentially calcified proximal LAD was grafted with a saphenous vein by carving an oval area of calcium creating an elliptical opening in the artery wall. Normal LV function returned and, in the area of the left main dissection, there was only thickening with no colour flow. Eight months postoperatively cardiac catheterization showed normal LV function, patent vein grafts to the right coronary artery and proximal LAD, left internal mammary artery to distal LAD and an occluded sequential marginal vein graft. Twelve years postoperatively, the patient is well with Class I angina, on medication. There is no previous documentation of a diagnosed and successfully treated left main dissection during CABG surgery. Since this case using the technique of creating an oval opening in a circumferentially calcified coronary artery (with an otherwise satisfactory lumen), the author has been using this technique to bypass otherwise non-bypassable arteries; this technique may be useful to help patients with severe calcific coronary artery disease.

OBJECTIVES: Skeletonization of the internal mammary artery (IMA) facilitates arterial grafting and has been shown to reduce deep sternal infection but is more time-consuming and tedious than pedicle harvest. We wished to determine if use of harmonic technology (HT) facilitates skeletonization of the IMA and is as safe as the conventional technique of skeletonization. METHODS: In a consecutive series of 1057 patients with isolated coronary artery bypass graft (CABG) surgery from 2003 to 2013, adverse events and recorded harvest times were compared between harmonic (965 patients) and non-harmonic patients (86 patients). RESULTS: HT was used to harvest 1640 IMAs in 965 (91%) of 1057 consecutive CABG patients and skeletonization with the traditional technique (use of an electrocautery tip as a dissector) was used to harvest 147 IMAs in 86 patients. Six patients had no IMA harvested with this surgery (4 patients had an IMA used from a previous CABG, 1 had no disease of the left anterior descending coronary artery and 1 patient was in cardiogenic shock precluding IMA use). Excluding patients with single-vessel disease, 730/987 (74%) of patients received bilateral IMAs. Demographics of patients with and without harmonic skeletonization, respectively, were the following: mean age: 64.7 vs 67.7 years; diabetes: 33 vs 34%; women: 21 vs 26% and median European System for Cardiac Operative Risk Evaluation: 2.9 vs 3.2. The mean harvest time for 77 non-harmonic skeletonized mammary arteries (49 surgeries) was 32.2 min (95% confidence interval (CI): 30.1, 34.3), for harmonic skeletonized arteries after 450 surgeries was 28.4 min, (95% CI: 27.8, 29.1) and in the last 100 IMAs harvested for the isolated harmonic device use/mammary was 15.4 min (95% CI: 14.0, 16.7). Major adverse events for patients with and without harmonic skeletonization, respectively, were: reoperation for bleeding: 2.7 vs 3.5% (difference = 0.8%, 95% CI: −3.2, 4.8); damaged mammaries: 0.4 vs 0.7% (difference = 0.3%, 95% CI: −1.0, 1.7); deep sternal infection: 1.6 vs 1.2% (difference = −0.4%, 95% CI: −2.8, 2.0) and perioperative infarction: 1.7 vs 2.3% (difference = 0.7%, 95% CI: −2.6, 4.0). CONCLUSION: In this largest series to date of harmonic IMA skeletonization, this technique results in rare damage, is quicker and with a comparable adverse event rate compared with the non-harmonic method.

Background The efficacy of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in patients with coronary artery disease has been well defined by randomized controlled trials. However, patients with severe left ventricular dysfunction (ejection fraction Methods The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and outcome monitoring initiative for the province of Alberta, Canada, was used to identify 2925 patients with coronary artery disease and left ventricular dysfunction undergoing CABG (n = 1,326) or PCI (n = 1,599) between 1995 and 2008. Patients were propensity matched to obtain comparable subgroups among left ventricular dysfunction patients. Results Cox proportional hazard analysis of the propensity-matched subgroups identified that CABG was significantly associated with lower rates of repeat revascularization and better survival compared with PCI at 1, 5, 10, and 15 years. Other significant independent predictors of poor long-term survival included age, renal failure, heart failure, diabetes mellitus, peripheral vascular disease, prior myocardial infarction, left main coronary artery disease, and prior CABG. Conclusions For patients with coronary artery disease and left ventricular dysfunction, CABG was associated with lower rates of repeat revascularization and improved survival over PCI, after adjustment for baseline risk profile differences. Further research exploring the factors leading to use of a particular revascularization modality in this patient population is required.

textabstractPurpose of Review: Arterial grafting is superior to venous grafting in coronary artery bypass graft surgery with respect to graft patency and long-term patient outcome, but it may be difficult to achieve complete arterial revascularization. Recent Findings: Use of arterial grafts, especially bilateral internal mammary artery grafts, is not common, whereas there are clear indications that it may increase survival. Definitions of complete revascularization are varied and confusing, making study comparisons difficult. Technical challenges in complete revascularization with arterial grafts can be minimized by surgical techniques. Competitive flow in moderately stenosed coronary arteries grafted with arterial conduits may result in reduced patency. While internal mammary arteries may be used in arteries with at least 60% stenosis, radial artery and gastroepiploic grafts are best placed onto coronaries with severe stenosis. Moderate lesions in the left coronary circulation should be bypassed, but right coronary artery lesions can be left untouched as there is minimal progression over time. Complete revascularization may not be necessary or possible in every patient because of technical challenges. CONCLUSION: Complete revascularization with arterial grafts presents both technical and physiological challenges. However, with techniques to maximize length of arterial conduits, knowledge of competitive flow and which moderate lesions should be addressed, complete revascularization with arterial grafts can be accomplished in the majority of patients, notwithstanding it may not be possible or even indicated for every patient.

OBJECTIVES: The purpose of this study was to compare effectiveness of the 1999 logistic EuroSCORE (LES) and of the 2012 EuroSCORE II (ESII) in a real-world patient population of 1125 patients undergoing total arterial grafting (TAG) coronary artery bypass graft (CABG) surgery. METHODS: The performance of the two risk scores was compared using (i) discrimination (accuracy of discriminating non-survivors from survivors), (ii) calibration (assessment of agreement between the predicted/observed outcomes) and (iii) agreement between the two scores. By averaging medians of LES and ESII and then sub-division into 10 equal groups, actual operative mortality rate was compared with the median LES and ESII within each risk group, the difference plotted against the average risk score (as in a Bland and Altman plot), and using the traditional risk groupings for EuroSCORE of low (0-2.99), medium (3-5.99) and high risk (6.0 and above), the reclassification rate of ESII was compared with that of LES. RESULTS: In 1125 consecutive total arterial CABG patients, demographics included: mean age 64.6 years, 79% males, 35% diabetic patients, 57% urgent/emergent patients, 37% off-pump and 77% bilateral mammary grafting. Overall operative mortality was 3.2% (36 patients). Comparison of the LES and ESII showed (i) good discrimination for both LES and ESII (area under the curve for LES was 0.85 and for ESII was 0.87); (ii) neither score was well calibrated: LES tended to overestimate and ESII underestimated risk. In general, the ESII provided a better estimate of risk in lower risk patients and LES was better for the highest risk group. (iii) In terms of agreement, in the lower four risk groups the risk was overestimated by both scores, in five of the higher six risk groups ESII underestimated risk and LES overestimated risk, and in the highest risk group LES was very close (17.2 cf. 17.7) compared with ESII (5.6 cf. 17.7). In addition, ESII downgraded risk in 96.8% of survivors and in 97.2% of non-survivors. CONCLUSIONS: In 1125 consecutive TAG CABG patients, neither LES nor ESII performed well enough to be used as a consistent risk stratification tool; LES overestimated risk but was highly accurate for the highest of 10 risk groups and ESII consistently underestimated risk in all patients.

Background: Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery. Methods: Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization. Results: We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval [CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31). Interpretation: Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. NCT01071265.

Action of the uppermost medial internal intercostal muscles-the parasternals-during rapid eye movement (REM) is uncertain; no direct recordings exist of shortening of these muscles during sleep. Historically, motor inhibition of skeletal muscles during REM sleep is thought to cause global loss of chest wall muscle function, REM "atonia," with preservation of only diaphragm function. However, recent evidence during wakefulness shows parasternals as distinctive obligatory inspiratory muscles. Therefore we hypothesized that attenuation of chest wall function during sleep may spare the parasternals along with the diaphragm, as essential muscles of inspiration during REM. We studied seven canines, comparing costal and crural diaphragm and parasternal intercostal muscle function during wakefulness and non-REM (NREM) and REM sleep, during normal spontaneous sleep, continuously recording ventilation and simultaneous muscle electromyogram (EMG) and length from sonomicrometry microtransducers. Ventilation during sleep declined significantly from wakefulness. From wakefulness to NREM and REM, costal and crural tidal EMG increased, while parasternal tidal EMG was preserved unchanged. Costal and crural shortening per breath during NREM and REM did not change significantly from wakefulness. Concurrently, parasternal shortening decreased equally in both NREM and REM despite preservation of the parasternal EMG. We conclude that diaphragm and parasternals are not inhibited, and both remain active together as essential inspiratory muscles, during REM sleep. The lesser contraction of parasternal intercostals compared with diaphragm may be attributed to net changes in mechanics affecting the chest wall during sleep.

Objective Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS(R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well. Methods We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult out-patients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS(R) 5570, WS(R) 5572, WS(R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained > or = 50 % decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of > or =20 % HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement'). Results For Hypericum extract, early improvement had a sensitivity of 87 % (95 % confidence interval [CI], 82-93 %) and a specificity of 54 % (95 % CI, 45-62 %) at day 14, and a sensitivity of 43 % (95 % CI, 35-51 %) and a specificity of 86 % (95 % CI, 80-92 %) at day 7 for predicting sustained response. After 2 weeks of treatment, 78 % (95 % CI, 69-87 %) of the patients who failed to improve did not show sustained response later during treatment. Conclusion A substantial fraction of the patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.

Summary Objective: Information about adverse drug reactions plays an important role when assessing the benefit/risk profile of a drug. Identifying rare adverse drug reactions, however, is a difficult task. This paper illustrates the advantages of using a prescription database for this purpose. Methods: The mediplus® database used in our analysis covered data from 320,644 outpatients observed between July 1999 and June 2002. The example of bleeding complications during intake of antidementia drugs is used to illustrate this approach. The comparison of cohorts and subgroups is nearly always a problem in surveys. For our analyses we considered a set of patients who had taken a selected medication for a certain period of time and compared the frequency of adverse events with those occurring when the same patients did not take this medication. Hence, the comparison with versus without a certain medication is based on the same set of patients as in a cross-over study. Results: Our evaluations indicate that the rate of bleeding complications is low when taking any of the widely used antidementia drugs, glutamate modulators, cholinesterase inhibitors, calcium antagonists or the phytomedicine Ginkgo biloba. Conclusion: Basing the comparison of the rates of complications during periods with and without intake of a certain drug on the same set of patients may be a useful tool for assessing adverse drug reactions from data reported in prescription databases.

Objective: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. Methods: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ETA/B receptor antagonist, 3 μM), BQ-123 (ETA antagonist, 1 μM) and BQ-788 (ETB antagonist, 1 μM) using the isolated organ bath apparatus. Percent maximum relaxation (% E max) and sensitivity (pEC50) were compared between interventions. Results: ACh caused dose-dependent endothelium-mediated relaxation in IMA (% E max 43±4, pEC50 6.74±0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (% E max bosentan 60±3, BQ-123 56±4, BQ-788 53±5 vs. control 43±4, P 0.05). Conclusions: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female out-patients suffering from mild or moderate depression according to DSM-IV criteria. Fifty-six (38.1%) of them had an initial total score ≥ 22 points on the Hamilton Rating Scale for Depression (HAMD, 17-item version). Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3×1 tablet of either placebo, Hypericum extract WS 5573 (300mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for both Hypericum preparations was identical, they only differed with regard to their content of hyperforin. Efficacy regarding depressive symptoms was assessed on days 0, 7,14,28, and 42. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 ± 4.6 points; mean ± SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 ± 6.1 points) and the placebo group (7.9 ± 5.2 points). The monotonie trend was significant (Jonckheere-Terpstra test; p = 0.017). In patients with an initial HAMD total score ≥ 22, the HAMD reduction was even by 16.5% larger than in the total study group receiving WS 5572. More severely depressed patients treated with WS 5573, however, showed a 22.4% lower reduction of the HAMD total score than the entire WS 5573 treatment group. In patients with HAMD ≥ 22, WS 5572 showed a 53.8% larger HAMD reduction than placebo, whereas WS 5573 was not relevantly different from the placebo level. The mean HAMD reductions, treatment end versus baseline, for the more severely depressed patients were 12.0 (3.7) points, 6.6 (7.7) points and 7.8 (5.4) points [mean (SD)] for WS 5S72, WS 5573 and placebo, respectively. The results of a responder analysis support these findings. The data point to a dose-response relationship between the antidepressant efficacy of Hypericum extract and its hyperforin content. The extract with a higher content of hyperforin was particularly effective in patients who were more severely depressed.

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female outpatients suffering from mild or moderate depression according to DSM-IV criteria. Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3 x 1 tablets of either placebo, Hypericum extract WS 5573 (300 mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for the two Hypericum preparations was identical, so that they differed only in their hyperforin content. Efficacy regarding depressive symptoms was assessed on days 0, 7, 14, 28, and 42, using the Hamilton Rating Scale for Depression (HAMD, 17-item version) and the Depression Self-Rating Scale (D-S) according to von Zerssen. In addition, the severity of illness was also rated by the investigators on days 0 and 42 using the Clinical Global Impression (CGI) scale. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 +/- 4.6 points; mean +/- SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 +/- 6.1 points) and the placebo group (7.9 +/- 5.2 points). As regards the change in the HAMD total score between day 0 and treatment end and its relationship to the hyperforin dose, a significant monotonic trend was demonstrated in the Jonckheere-Terpstra test (p = 0.017). In pairwise comparisons, WS 5572 (5% hyperforin) was superior to placebo in alleviating depressive symptoms according to HAMD reduction (Mann-Whitney U-test: p = 0.004), whereas the clinical effects of WS 5573 (0.5% hyperforin) and placebo were descriptively comparable. These results show that the therapeutic effect of St. John's Wort in mild to moderate depression depends on its hyperforin content.

Pulmonary complications after upper abdominal surgery are usually ascribed to temporary postoperative impairment of diaphragm function, which may not originate from intrinsic, structural injury but from reflex inhibition of diaphragm contractility. Spontaneous breathing is interrupted periodically by sighs, even after upper abdominal surgery. If postoperative dysfunction of the diaphragm arises from a reflexic inhibition, then the sigh should temporarily override the inhibition and restore normal diaphragm function. We implanted sonomicrometer and electromyogram transducers chronically in six dogs by laparotomy, then directly measured length, shortening, and electromyogram activity of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis muscles an average of 8.7 (range, 1-16) d later during resting tidal breathing and sighs. In each animal we analyzed a sequence of breaths, including a sigh, when costal or crural diaphragm contractility was abnormal. With each sigh, the shape and amplitude of costal and crural diaphragm segmental shortening improved abruptly, from 0.9 and 1.4% of baseline length (% LBL) during resting breathing to 12.1 and 11.1% LBL, respectively, during sighs. The sighs were compared to CO2-stimulated breaths of equivalent tidal volume, which did not show either pattern or amplitude of shortening equivalent to sighs. We conclude that diaphragm dysfunction after laparotomy arises from a reflex inhibition, which is overridden abruptly to return diaphragm function briefly to normal during each spontaneous sigh.

We tested the hypotheses that a dual-chamber pacemaker that paces when intrinsic rate drops abruptly would reduce the number of syncopal spells and improve the quality of life in patients with highly recurrent neurally mediated syncope. Twelve patients with highly frequent neurally mediated syncope and at least 1 syncopal spell after tilt testing received dual-chamber pacemakers with automatic rate-drop sensing. The pacemakers were implanted 17+/-26 months after tilt testing, and the patients then were followed for 12+/-2 months. We compared the time to the first recurrence of syncope, syncope frequency, and quality of life for the 2 periods between tilt testing and pacemaker implantation, and between implantation and last follow-up. Only 6 of 12 patients fainted after pacemaker insertion. The median time to syncope recurrence before and after pacing was 7 days and 5.3 months, respectively. The geometric mean frequency of faints before and after pacing was 5.0 spells/month (95% confidence interval 2.7 to 9.2) and 0.30 spells/month (95% confidence interval 0.2 to 0.4), p0.001. After 6 months the mean perception of health on the 100-point EuroQol scale rose from 55 to 82 (p = 0.003), and the general health perception on the SF-36 scale rose from 51 to 72 (p = 0.005). Permanent dual-chamber pacing with automatic rate-drop sensing in patients with highly frequent syncope is associated with a marked reduction in the likelihood of syncope and a marked improvement in quality of life.