DEtection of ProxImal Coronary stenosis in the work-up for Transcatheter aortic valve implantation using CTA (from the DEPICT CTA collaboration).

OBJECTIVES: Computed tomography angiography (CTA) is performed routinely in the work-up for transcatheter aortic valve implantation (TAVI), and could potentially replace invasive coronary angiography (ICA) to rule out left main (LM) and proximal coronary stenosis. The objectives were to assess the diagnostic yield and accuracy of pre-TAVI CTA to detect LM and proximal coronary stenosis of ≥ 50% and ≥ 70% diameter stenosis (DS). METHODS: The DEPICT CTA database consists of individual patient data from four studies with a retrospective design that analyzed the diagnostic accuracy of pre-TAVI CTA to detect coronary stenosis, as compared with ICA. Pooled data were used to assess diagnostic accuracy to detect coronary stenosis in the left main and the three proximal coronary segments on a per-patient and a per-segment level. We included 1060 patients (mean age: 81.5 years, 42.7% male). RESULTS: On ICA, the prevalence of proximal stenosis was 29.0% (≥ 50% DS) and 15.7% (≥ 70% DS). Pre-TAVI CTA ruled out ≥ 50% DS in 51.6% of patients with a sensitivity of 96.4%, specificity of 71.2%, PPV of 57.7%, and NPV of 98.0%. For ≥ 70% DS, pre-TAVI CTA ruled out stenosis in 70.0% of patients with a sensitivity of 96.7%, specificity of 87.5%, PPV of 66.9%, and NPV of 99.0%. CONCLUSION: CTA provides high diagnostic accuracy to rule out LM and proximal coronary stenosis in patients undergoing work-up for TAVI. Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of patients, using a threshold of ≥ 50% or ≥ 70% DS, respectively. KEY POINTS: • Clinical application of CTA as a gatekeeper for ICA would reduce the need for ICA in 52% or 70% of TAVI patients, using a threshold of ≥ 50% or ≥ 70% diameter stenosis. • The diagnostic accuracy of CTA to exclude proximal coronary stenosis in these patients is high, with a sensitivity of 96.4% and NPV of 98.0% for a threshold of ≥ 50%, and a sensitivity of 96.7% and NPV of 99.0% for a threshold of ≥ 70% diameter stenosis. • Atrial fibrillation and heart rate did not significantly affect sensitivity and NPV. However, a heart rate of < 70 b/min during CTA was associated with a significantly improved specificity and PPV.

Ectomycorrhiza resilience and recovery to extreme flood events in Tuber aestivum and Quercus robur.

Very little is known about the impact of flooding and ground saturation on ectomycorrhizal fungi (EcM) and increasing flood events are expected with predicted climate change. To explore this, seedlings inoculated with the EcM species Tuber aestivum were exposed to a range of flood durations. Oak seedlings inoculated with T. aestivum were submerged for between 7 and 65 days. After a minimum of 114-day recovery, seedling growth measurements were recorded, and root systems were destructively sampled to measure the number of existing mycorrhizae in different zones. Number of mycorrhizae did not display correlation with seedling growth measurements. Seven days of submersion resulted in a significant reduction in mycorrhizae numbers and numbers reduced most drastically in the upper zones. Increases in duration of submersion further impacted mycorrhizae numbers in the lowest soil zone only. T. aestivum mycorrhizae can survive flood durations of at least 65 days. After flooding, mycorrhizae occur in higher numbers in the lowest soil zone, suggesting a mix of resilience and recovery. The results will aid in furthering our understanding of EcM but also may aid in conservation initiatives as well as providing insight for those whose livelihoods revolve around the collection of EcM fruiting bodies or cropping of the plant partners.

Long-term outcomes of biological mesh repair following extra levator abdominoperineal excision of the rectum: an observational study of 100 patients.

BACKGROUND: Current evidence suggests that pelvic floor reconstruction following extralevator abdominoperineal excision of rectum (ELAPER) may reduce the risk of perineal herniation of intra-abdominal contents. Options for reconstruction include mesh and myocutaneous flaps, for which long-term follow-up data is lacking. The aim of this study was to evaluate the long-term outcomes of biological mesh (Surgisis®, Biodesign™) reconstruction following ELAPER. METHODS: A retrospective review of all patients having ELAPER in a single institution between 2008 and 2018 was perfomed. Clinic letters were scrutinised for wound complications and all available cross sectional imaging was reviewed to identify evidence of perineal herniation (defined as presence of intra-abdominal content below a line between the coccyx and the lower margin of the pubic symphysis on sagittal view). RESULTS: One hundred patients were identified (median age 66, IQR 59-72 years, 70% male). Median length of follow-up was 4.9 years (IQR 2.3-6.7 years). One, 2- and 5-year mortality rates were 3, 8 and 12%, respectively. Thirty three perineal wounds had not healed by 1 month, but no mesh was infected and no mesh needed to be removed. Only one patient developed a symptomatic perineal hernia requiring repair. On review of imaging a further 7 asymptomatic perineal hernias were detected. At 4 years the cumulative radiologically detected perineal hernia rate was 8%. CONCLUSIONS: This study demonstrates that pelvic floor reconstruction using biological mesh following ELAPER is both safe and effective as a long-term solution, with low major complication rates. Symptomatic perineal herniation is rare following mesh reconstruction, but may develop sub clinically and be detectable on cross-sectional imaging.

Recurrent myocardial infarction in a 47-year-old woman with a mechanical mitral valve prosthesis: Atherosclerosis, embolism, or spasm?

We present a case of a 47-year-old woman with a mechanical mitral valve prosthesis and recurrent myocardial infarction. The most common etiology of spontaneous myocardial infarction is an acute coronary syndrome caused by rupture or erosion of an atherosclerotic plaque. However, the differential diagnosis in the patient described below also included infarction due to embolization or coronary spasm. It can be challenging to discriminate between the different causes of myocardial infarction based on interpretation of symptoms, physical examination, laboratory tests, and electrocardiography alone. This report illustrates the value of coronary angiography with invasive coronary spasm provocation testing using intracoronary acetylcholine to identify the etiology of her recurrent myocardial infarctions.

Influence of process dynamics on the microbial diversity in a nitrifying biofilm reactor: Correlation analysis and simulation study.

For engineers, it is interesting to gain insight in the effect of control strategies on microbial communities, on their turn influencing the process behavior and its stability. This contribution assesses the influence of process dynamics on the microbial community in a biofilm reactor for nitrogen removal, which was controlled according to several strategies aiming at nitrite accumulation. The process dataset, combining conventional chemical and physical data with molecular information, was analyzed through a correlation analysis and in a simulation study. During nitrate formation, an increased nitrogen loading rate (NLR) resulted in a drop of the bulk liquid oxygen concentration without resulting in nitrite accumulation. A biofilm model was able to reproduce the bulk liquid nitrogen concentrations in two periods before and after this increased NLR. As the microbial parameters calibrated for the ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in both periods were different, it was concluded that the increased NLR governed an AOB and NOB population shift. Based on the molecular data, it was assumed that each period was typified by one dominant AOB and probably several subdominant NOB populations. The control strategies for nitrite accumulation influenced the bulk liquid composition by controlling the competition between AOB and NOB. Biotechnol. Bioeng. 2016;113: 1962-1974. © 2016 Wiley Periodicals, Inc.

Considering microbial and aggregate heterogeneity in biofilm reactor models: how far do we need to go?

A model describing a given system should be as simple as possible - but not simpler. The appropriate level of complexity depends both on the type of system and on the intended use of the model. This paper addresses the critical question of which purposes justify increased complexity of biofilm (reactor) models. Additional model features compared to conventional models considered are: (1) the inclusion of microbial diversity, distinguishing between different species performing the same function; and (2) the distinction between flocs and granules in putatively granular sludge reactors. With a multispecies model considering interspecies diversity, it was demonstrated that a given macroscopic reactor performance does not necessarily reflect steady state conditions on the microscale. In a second case study, it was shown that the addition of a small level of flocs can have a significant impact on macroscale process performance and on microbial population and activity distributions in granular sludge reactors. It was concluded that increased complexity in biofilm models, concerning microbial diversity or mesoscale aggregate architecture, is likely more useful when the focus is on understanding fundamental microscale outputs, but under specific conditions, these additional model features can be critically informative for bulk reactor behavior prediction and general understanding.

A comparison of intramuscular diamorphine and intramuscular pethidine for labour analgesia: a two-centre randomised blinded controlled trial.

OBJECTIVE: Intramuscular (i.m.) pethidine is used worldwide for labour analgesia and i.m. diamorphine usage has increased in the UK in the last 15 years. This trial aims to ascertain the relative efficacy and adverse effects of diamorphine and pethidine for labour pain. DESIGN: Prospective, parallel-arm randomised controlled trial with blinding of participants, care-givers and outcome assessors. SETTING: Maternity units in two District General Hospitals in the UK. POPULATION: After written informed consent, 484 women were randomised and recruited (244 diamorphine, 240 pethidine). Inclusion criteria included women 16 years or older, established labour, singleton pregnancy, 37-42 weeks of gestation and weight 60-120 kg. METHODS: On request of i.m. analgesia, participants received either 150 mg pethidine or 7.5 mg diamorphine based on computer-generated block randomisation. MAIN OUTCOME MEASURES: Maternal-reduction in pain intensity from baseline (10-cm visual analogue scale) at 60 minutes and over the 3-hour period after drug administration. Neonatal-requirement for resuscitation and Apgar score at 1 minute. RESULTS: Diamorphine provided modestly improved pain relief at 60 minutes, mean difference 1 cm (95% confidence interval [CI] 0.5-1.5), and over the 3 hours, mean difference 0.7 cm (95% CI 0.3-1.1). However, average length of labour in women receiving diamorphine was 82 minutes longer (95% CI 39-124) and therefore they experienced more pain overall. There were no statistically significant differences in primary neonatal outcomes. CONCLUSIONS: There is a modest difference between the analgesia provided by diamorphine or pethidine for labour analgesia but diamorphine is associated with significantly longer labours.

A national survey of obstetric early warning systems in the United Kingdom: five years on.

The Confidential Enquiries into Maternal Deaths in the UK have recommended obstetric early warning systems for early identification of clinical deterioration to reduce maternal morbidity and mortality. This survey explored early warning systems currently used by maternity units in the UK. An electronic questionnaire was sent to all 205 lead obstetric anaesthetists under the auspices of the Obstetric Anaesthetists' Association, generating 130 (63%) responses. All respondents reported use of an obstetric early warning system, compared with 19% in a similar survey in 2007. Respondents agreed that the six most important physiological parameters to record were respiratory rate, heart rate, temperature, systolic and diastolic blood pressure and oxygen saturation. One hundred and eighteen (91%) lead anaesthetists agreed that early warning systems helped to prevent obstetric morbidity. Staffing pressures were perceived as the greatest barrier to their use, and improved audit, education and training for healthcare professionals were identified as priority areas.

A comparison of pre-operative nerve stimulator-guided femoral nerve block and fascia iliaca compartment block in patients with a femoral neck fracture.

We undertook a randomised, controlled trial to compare the analgesic efficacy and opioid sparing effect of nerve stimulator-guided femoral nerve block with fascia iliaca compartment block in patients awaiting surgery for fractured neck of femur. Ten-centimetre visual analogue pain scores were measured before and 2 h after the block and opioid consumption was recorded in the 12-h period after the block. One hundred and ten patients were randomly assigned. Femoral nerve block provided superior pre-operative analgesia for fractured neck of femur compared with fascia iliaca compartment block. The difference in the mean reduction of pain score after the block was 0.9 (95% CI 0-1.8); p = 0.047. Patients receiving a femoral nerve block required less morphine after the block than those receiving fascia iliaca compartment block (p = 0.041).

Poor numeracy skills are associated with glycaemic control in Type 1 diabetes.

AIMS: To assess the numeracy and literacy skills of individuals with Type 1 diabetes and determine if there is a relationship with achieved glycaemic control independent of their duration of diabetes, diabetes education, demographic and socio-economic factors. METHODS: One hundred and twelve patients completed the study (mean current age 43.8 ± 12.5 years, 47% male, mean duration of diabetes 22.0 ± 13.2 years) out of 650 randomly selected patients from the Bournemouth Diabetes and Endocrine Centre's diabetes register. The Skills for Life Initial Assessments were used to measure numeracy and literacy. These indicate skills levels up to level 2, equivalent to the national General Certificate of Secondary Education grades A*-C. HbA(1c) was also measured. Pearson's correlation was used to measure the correlation of numeracy and literacy scores with HbA(1c.) To compare mean HbA(1c) between those with or without level 2 skills, t-tests were used, and multiple linear regression was used to investigate whether any differences were independent of duration of diabetes, diabetes education, demographic and socio-economic factors. RESULTS: Literacy was not associated with achieved HbA(1c). In contrast, participants with numeracy skills at level 2 or above achieved an HbA(1c) lower than those with numeracy skills below level 2 (P = 0.027). Although higher socio-economic status was associated with lower mean HbA(1c) , the relationship between numeracy and HbA(1c) appeared to be independent of socio-economic factors. CONCLUSIONS: Low numeracy skills were adversely associated with diabetes control. Assessment of numeracy skills may be relevant to the structure of diabetes education programmes.

Deep learning-based whole-heart segmentation in 4D contrast-enhanced cardiac CT.

Automatic cardiac chamber and left ventricular (LV) myocardium segmentation over the cardiac cycle significantly extends the utilization of contrast-enhanced cardiac CT, potentially enabling in-depth assessment of cardiac function. Therefore, we evaluate an automatic method for cardiac chamber and LV myocardium segmentation in 4D cardiac CT. In this study, 4D contrast-enhanced cardiac CT scans of 1509 patients selected for transcatheter aortic valve implantation with 21,605 3D images, were divided into development (N = 12) and test set (N = 1497). 3D convolutional neural networks were trained with end-systolic (ES) and end-diastolic (ED) images. Dice similarity coefficient (DSC) and average symmetric surface distance (ASSD) were computed for 3D segmentations at ES and ED in the development set via cross-validation, and for 2D segmentations in four cardiac phases for 81 test set patients. Segmentation quality in the full test set of 1497 patients was assessed visually on a three-point scale per structure based on estimated overlap with the ground truth. Automatic segmentation resulted in a mean DSC of 0.89 ± 0.10 and ASSD of 1.43 ± 1.45 mm in 12 patients in 3D, and a DSC of 0.89 ± 0.08 and ASSD of 1.86 ± 1.20 mm in 81 patients in 2D. The qualitative evaluation in the whole test set of 1497 patients showed that automatic segmentations were assigned grade 1 (clinically useful) in 98.5%, 92.2%, 83.1%, 96.3%, and 91.6% of cases for LV cavity and myocardium, right ventricle, left atrium, and right atrium. Our automatic method using convolutional neural networks performed clinically useful segmentation across the cardiac cycle in a large set of 4D cardiac CT images, potentially enabling in-depth assessment of cardiac function.

HbA1c 3 months after diagnosis predicts premature mortality in patients with new onset type 2 diabetes.

AIMS: To determine 5-year mortality rates, following the diagnosis of Type 2 diabetes, in a large local cohort of individuals with new onset of Type 2 diabetes seen within a few weeks of diagnosis in a single, community-based education programme. METHODS: We reviewed referrals for people with Type 2 diabetes to our service over 5 years from 1999 to 2003 and determined, via regression analysis, which factors contributed significantly to mortality rates up to the end of 2007. RESULTS: A total of 3781 new referrals were reviewed with an approximate doubling of referral rates over 5 years (546 in 1999-997 in 2003). Although the number of people developing the condition has increased, mortality rates over the 5 years from diagnosis has fallen from 11% in 1999-9% in 2003 (P < 0.005) Age at diagnosis was the strongest predictor of mortality (P < 0.001) but HbA(1c) at 3 months after diagnosis (P < 0.001), systolic (P < 0.001) and diastolic (P = 0.05) blood pressure, smoking status (P < 0.001) and gender (P = 0.04) were also significant predictors. CONCLUSIONS: Our retrospective analysis adds weight to evidence suggesting that referral rates for people with Type 2 diabetes are increasing rapidly and that mortality rates are reducing but that the reasons for this are multifactorial. In addition to blood pressure, smoking and gender, the HbA(1c) achieved 3 months after the initial diagnosis also appears to predict subsequent mortality. It may be appropriate to consider early and intensive intervention for individuals with new onset type 2 diabetes.

Patient-tailored Contrast Delivery Protocols for Computed Tomography Coronary Angiography: Lower Contrast Dose and Better Image Quality.

PURPOSE: The first objective of this study was to evaluate the efficacy of a patient-tailored contrast delivery protocol for coronary computed tomography angiography (CTCA), in terms of diagnostic coronary attenuation and total iodine load (TIL), by adjusting the iodine delivery rate (IDR) via dilution for body weight and tube voltage (kV), as compared with a protocol with a fixed bolus of contrast in a clinical setting. The secondary objective was to assess the association between the test-bolus data and luminal attenuation in CTCA. MATERIALS AND METHODS: Patients who underwent CTCA with fixed IDR contrast delivery (cohort 1) or with IDR adjusted for body weight and kV settings (70 to 120 kV) (cohort 2) were included, and compared for intravascular luminal attenuation and TIL. The association between intravascular luminal attenuation and test-bolus scan data was investigated with linear regression. RESULTS: In cohort 1 (176 patients), the mean luminal attenuation differed markedly between kV categories, whereas in cohort 2 (154 patients), there were no marked differences. The mean TIL reduced significantly (20.1±1.2 g in cohort 1, 17.7±3.0 g in cohort 2, P<0.001). The peak height of the test-bolus scan was independently associated with luminal attenuation in the ascending aorta, with a 0.58 HU increase per HU peak-height increase (SE=0.18, P<0.001). CONCLUSION: Clinical implementation of a patient-tailored contrast delivery protocol for CTCA, adjusted for body weight and kV, improves luminal attenuation and significantly reduces the TIL. The peak height of the test-bolus scan is associated with luminal attenuation in the ascending aorta in the CTCA scan.

Implementation of CT Coronary Angiography as an Alternative to Invasive Coronary Angiography in the Diagnostic Work-Up of Non-Coronary Cardiac Surgery, Cardiomyopathy, Heart Failure and Ventricular Arrhythmias.

To assess the need for additional invasive coronary angiography (CAG) after initial computed tomography coronary angiography (CTCA) in patients awaiting non-coronary cardiac surgery and in patients with cardiomyopathy, heart failure or ventricular arrhythmias, and to determine differences between patients that were referred to initial CTCA or direct CAG, consecutive patients were included between August 2017 and January 2020 and categorized as those referred to initial CTCA (conform protocol), and to direct CAG (non-conform protocol). Out of a total of 415 patients, 78.8% (327 patients, mean age: 57.9 years, 67.3% male) were referred to initial CTCA, of whom 260 patients (79.5%) had no obstructive lesions (<50% DS). A total of 55 patients (16.8%) underwent additional CAG after initial CTCA, which showed coronary lesions of >50% DS in 21 patients (6.3% of 327). Eighty-eight patients (mean age: 66.0 years, 59.1% male) were directly referred to CAG (non-conform protocol). These patients were older and had more cardiovascular risk factors compared to patients that underwent initial CTCA (conform protocol), and coronary lesions of >50% DS were detected in 16 patients (17.2%). Revascularization procedures were infrequently performed in both groups: initial CTCA (3.0%), direct CAG (3.4%). The use of CTCA as a gatekeeper CAG in the diagnostic work-up of non-coronary cardiac surgery, cardiomyopathy, heart failure and ventricular arrhythmias is feasible, and only 17% of these patients required additional CAG after initial CTCA. Therefore, CTCA should be considered as the initial imaging modality to rule out CAD in these patients.

The Impact of Percutaneous Coronary Intervention on Mortality in Patients With Coronary Lesions Who Underwent Transcatheter Aortic Valve Replacement.

OBJECTIVES: To analyze the effect of percutaneous coronary intervention (PCI) before transcatheter aortic valve replacement (TAVR) on all-cause and cardiovascular mortality after TAVR, differentiating between significant proximal lesions and the non-proximal (residual) lesions. METHODS: An institutional TAVR database was complemented with data on the extent of coronary artery disease (CAD), lesion location, lesion severity, and the location of PCI. Survival analysis was performed to investigate the impact on 6-month and 3-year mortality after TAVR in all patients and in subgroups of patients with significant proximal lesions (>70% diameter stenosis [DS], >50% DS in left main), the non-proximal residual lesions, and in a propensity score matched cohort. RESULTS: Among the 577 included patients, mean age was 83 years, 50% were female, and 31% had diabetes mellitus. Preprocedural PCI of unselected lesions was independently associated with increased 6-month mortality (hazard ratio, 2.2; 95% confidence interval, 1.0-4.6; P=.04), but selective PCI of significant proximal lesions did not have an association with higher mortality, nor did we find a significant effect of PCI on mortality in the propensity-matched cohort. CONCLUSION: Routine pre-TAVR PCI is not associated with mortality reduction in TAVR patients with coronary lesions in any segment or in patients with proximal coronary lesions. Despite the lack of a beneficial effect of routine pre-TAVR PCI, we cannot exclude a beneficial effect in a selection of patients with proximal lesions. Therefore, we strongly support the current clinical guidelines to only consider pre-TAVR PCI in proximal coronary lesions, while advocating a restrictive pre-TAVR PCI strategy.

Balloon-Expandable TAVR Prosthesis Dislocates Into the Ascending Aorta.

This case report underlines the complexity of the transcatheter aortic valve replacement (TAVR) procedure where rare complications sometimes are inevitable, even in experienced hands. Supra-annular dislocation of the balloon-expandable prosthesis was caused by loss of capture of the temporary transvenous pacemaker lead and treated successfully by retracting it towards the abdominal aorta. (Level of Difficulty: Advanced.).

Quantification of Myocardial Mass Subtended by a Coronary Stenosis Using Intracoronary Physiology.

BACKGROUND: In patients with stable coronary artery disease, the amount of myocardium subtended by coronary stenoses constitutes a major determinant of prognosis, as well as of the benefit of coronary revascularization. We devised a novel method to estimate partial myocardial mass (PMM; ie, the amount of myocardium subtended by a stenosis) during physiological stenosis interrogation. Subsequently, we validated the index against equivalent PMM values derived from applying the Voronoi algorithm on coronary computed tomography angiography. METHODS: Based on the myocardial metabolic demand and blood supply, PMM was calculated as follows: PMM (g)=APV×D2×π/(1.24×10-3×HR×sBP+1.6), where APV indicates average peak blood flow velocity; D, vessel diameter; HR, heart rate; and sBP, systolic blood pressure. We calculated PMM to 43 coronary vessels (32 patients) interrogated with pressure and Doppler guidewires, and compared it with computed tomography-based PMM. RESULTS: Median PMM was 15.8 g (Q1, Q3: 11.7, 28.4 g) for physiology-based PMM, and 17.0 g (Q1, Q3: 12.5, 25.9 g) for computed tomography-based PMM (P=0.84). Spearman rank correlation coefficient was 0.916 (P<0.001), and Passing-Bablok analysis revealed absence of both constant and proportional differences (coefficient A: -0.9; 95% CI, -4.5 to 0.9; and coefficient B, 1.00; 95% CI, 0.91 to 1.25]. Bland-Altman analysis documented a mean bias of 0.5 g (limit of agreement: -9.1 to 10.2 g). CONCLUSIONS: Physiology-based calculation of PMM in the catheterization laboratory is feasible and can be accurately performed as part of functional stenosis assessment.

Aortic valve calcification volumes and chronic brain infarctions in patients undergoing transcatheter aortic valve implantation.

Chronic silent brain infarctions, detected as new white matter hyperintensities on magnetic resonance imaging (MRI) following transcatheter aortic valve implantation (TAVI), are associated with long-term cognitive deterioration. This is the first study to investigate to which extent the calcification volume of the native aortic valve (AV) measured with cardiac computed tomography angiography (CTA) predicts the increase in chronic white matter hyperintensity volume after TAVI. A total of 36 patients (79 ± 5 years, median EuroSCORE II 1.9%, Q1-Q3 1.5-3.4%) with severe AV stenosis underwent fluid attenuation inversion recovery (FLAIR) MRI < 24 h prior to TAVI and at 3 months follow-up for assessment of cerebral white matter hyperintensity volume (mL). Calcification volumes (mm3) of the AV, aortic arch, landing zone and left ventricle were measured on the CTA pre-TAVI. The largest calcification volumes were found in the AV (median 692 mm3) and aortic arch (median 633 mm3), with a large variation between patients (Q1-Q3 482-1297 mm3 and 213-1727 mm3, respectively). The white matter hyperintensity volume increased in 72% of the patients. In these patients the median volume increase was of 1.1 mL (Q1-Q3 0.3-4.6 mL), corresponding with a 27% increase from baseline (Q1-Q3 7-104%). The calcification volume in the AV predicted the increase of white matter hyperintensity volume (Δ%), with a 35% increase of white matter hyperintensity volume, per 100 mm3 of AV calcification volume (SE 8.5, p < 0.001). The calcification volumes in the aortic arch, landing zone and left ventricle were not associated with the increase in white matter hyperintensity volume. In 72% of the patients new chronic white matter hyperintensities developed 3 months after TAVI, with a median increase of 27%. A higher calcification volume in the AV was associated with a larger increase in the white matter hyperintensity volume. These findings show the potential for automated AV calcium screening as an imaging biomarker to predict chronic silent brain infarctions.

Plasma concentrations and sedation scores after nebulized and intranasal midazolam in healthy volunteers.

BACKGROUND: An efficacious, reliable, and non-invasive route of administration for midazolam, a drug used for sedation and pre-anaesthetic medication, would have obvious advantages. This study compares two potential methods of administering midazolam by the nasal and nebulized routes. METHODS: Midazolam (0.2 mg kg(-1)) was given by both nebulizer and nasally by liquid instillation to 10 healthy volunteers in a randomized, double-blind crossover study. Plasma concentrations of midazolam, Ramsay sedation scores, visual analogue scores, critical flicker fusion frequency, and parameters of cardiovascular and respiratory function were measured over 60 min and summarized using 'area under the curve'. RESULTS: Nasal instillation caused more sedation than nebulized administration. This was demonstrated by higher Ramsay sedation scores (P=0.005), lower visual analogue scores (P<0.001), and lower critical flicker fusion frequency (P<0.02). Nasal instillation was associated with higher plasma concentrations of midazolam (P<0.001). Unpleasant symptoms were recorded by six volunteers in the intranasal and one in the nebulized group (P=0.06). CONCLUSIONS: There was some evidence that midazolam caused less discomfort when given by nebulizer compared with intranasally. Comparative bioavailability of midazolam, estimated by the ratio (nebulized:nasal) of area under the 60 min plasma concentration curve, was 1:2.9. A higher dose may need to be administered for adequate pre-anaesthetic medication when midazolam is given by nebulizer.