Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome: A Double-Blind, Randomized, Sham-Controlled Trial.

The Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome (CLIMACCS) trial, a randomized, sham-controlled trial, tested the clinical efficacy of permanent internal mammary artery (IMA) device occlusion on symptoms in patients with chronic coronary syndrome (CCS), coronary artery occlusive blood supply, and myocardial ischemia. This was a prospective trial in 101 patients with CCS randomly allocated (1:1) to IMA device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study end point was the change in treadmill exercise time (ET) (ΔET in seconds) at 6 weeks after trial intervention. Secondary study end points were the changes in collateral flow index (CFI) and angina pectoris during a simultaneous 1-minute proximal balloon occlusion of a coronary artery. CFI is the ratio between simultaneous mean coronary occlusive, divided by mean aortic pressure, both subtracted by central venous pressure. In the verum and placebo groups, the ET changed from 398 ± 176 seconds to 421 ± 198s in the verum group (p = 0.1745) and from 426 ± 162 seconds to 430 ± 166 seconds in the placebo group (p = 0.55); ΔET amounted to +23 ± 116s and +4 ± 120 seconds, respectively (p = 0.44). CFI change during follow-up equaled +0.022 ± 0.061 in the verum and -0.039 ± 0.072 in the placebo group (p <0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20 of 48 patients in the verum group and in 9 of 47 patients in the placebo group (p = 0.0242). In conclusion, permanent IMA device occlusion tends to augment treadmill ET in response to increased coronary artery occlusive blood supply, which is reflected by mitigated symptoms and signs of myocardial ischemia.

Blood Vessel Topography of the Feet in Selected Species of Birds of Prey and Owls.

Birds of prey and owls are susceptible to diseases of and traumatic injuries to their feet, which regularly require surgical intervention. A precise knowledge of the blood vessel topography is essential for a targeted therapy. Therefore, the metatarsal and digital vasculature was examined in eight species of birds of prey and owls. The study included contrast micro-computed tomography scans and anatomical dissections after intravascular injection of colored latex. In all examined species, the dorsal metatarsal arteries provided the main supply to the foot and their branching pattern and number differed between species. They continued distally as digital arteries. All examined species showed a basic pattern of four collaterally located digital blood vessels per toe: a prominent artery and small vein on one side and a small artery and prominent vein on the other side. Digital veins united to form common digital veins, most of which joined into a superficial, medially located metatarsal vein. This vein provided the main drainage of the foot. The detailed visualization of the topography of pedal blood vessels will help veterinary surgeons during surgical procedures. In addition, differences in the plantar arterial arch between hawks and falcons were discussed regarding their possible influence on the prevalence of pododermatitis (bumblefoot).

Aortic Valve Planimetry in Aortic Stenosis Quantification: Reliability of Three-Dimensional-Multiplane Reconstruction and Comparison With Established Methods.

We aim to evaluate the reliability and consistency of measuring the aortic valve area (AVA) using 3-dimensional (3D) transesophageal echocardiography and compare it with invasive and noninvasive methods using a continuity equation (CE). Measurements were taken from 119 patients with different severity of aortic stenosis and with normal aortic valve who underwent elective transesophageal echocardiography encompassing the whole spectrum of aortic opening. Three methods were compared to determine AVA. First, the effective AVA was calculated with the standard CE, where the left ventricular outflow tract area was calculated from its 2-dimensional diameter (AVA-CEstd). Second, a modified CE method (AVA-CEmod) was used, in which the left ventricular outflow tract area was measured using 3D-multiplane reconstruction. Third, the geometric AVA was directly measured using 3D-multiplane reconstruction planimetry (AVA-3D). Interobserver and intraobserver variability were analyzed using intraclass correlation coefficients (ICCs). The values were measured by two blinded readers for interobserver variability and by one observer on the same dataset. AVA-3D was significantly larger than AVA-CEmod and AVA-CEstd (1.87 ± 1.00 cm2 vs 1.81 ± 0.92 cm2 p = 0.03 and 1.87 ± 1.00 cm2 vs 1.71 ± 0.85 cm2 p <0.001). However, in the subset of patients with AVA-3D <1.5 cm2, there was no significant difference between AVA-3D and AVA-CEmod (1.06 ± 0.24 vs 1.08 ± 0.26 cm2, paired t test: t = 0.77, degree of freedom = 58, p = 0.44). The ICC between the measurements of AVA-3D and AVA-CEmod (ICC 0.979), and AVA-3D and AVA- CEstd (ICC 0.940), were excellent. AVA-3D delivers very similar results as compared with more established echocardiographic parameters. The difference between effective and geometric AVA did not appear to be clinically relevant in patients with a higher degree of stenosis.

Evidence for a sigmoidal flow-to-valve opening relation in low-flow low-gradient aortic stenosis.

We analyzed the relationship between flow (Q) and aortic valve opening area (AVA) using a sequence of echocardiographic stress tests of increasing strength. Low-dose dobutamine stress echocardiography (DSE) has been used to differentiate pseudo-severe from true severe aortic stenoses. Because the Q-response to DSE is so variable between individuals, AVA has been projected to a standardized flow (AVAproj) using linear interpolation. A linear Q-to-AVA relation implies that AVA shows an unconstrained increase. We applied three stress maneuvers of increasing strength to investigate whether AVA shows signs of saturation. We performed an echocardiographic examination at rest, during the passive leg raise maneuver ("PLR"), maximal dobutamine infusion ("Dmax"), and their combination ("Dmax + PLR") in 45 patients with severe low-flow, low-gradient aortic stenosis. We analyzed the effect of the stress maneuver on Q, AVA, valve compliance (VC), and AVAproj. We also compared the proportion of patients with nonconclusive test (ΔQ < 20%) between stress maneuvers. We computed the Akaike information criterion (AIC) to compare a linear with a saturating function for the Q-AVA relation. Q gradually increased from "PLR" to "Dmax" to "Dmax + PLR" (P < 0.0001), whereas the number of nonconclusive tests concomitantly diminished from n = 35 to n = 3. The stress sequence increased AVA (P < 0.001) but decreased AVAproj (P = 0.006) and VC (P = 0.005). In the pooled Q-AVA data, the AIC value was lower for the saturating (sigmoidal) model compared with the linear model fitting (-1,593 vs. -1,504). "Dmax + PLR" is capable of reducing the number of nonconclusive DSE tests. With increasing stress strength, the Q-AVA relation progressively flattens, indicating saturation.NEW & NOTEWORTHY The relation between transaortic flow (Q) and aortic valve opening area (AVA) shows a saturation when three different stress maneuvers are used to increase Q as much as possible. This has implications for the assessment of aortic stenosis severity.

Predicting progression of aortic stenosis by measuring serum calcification propensity.

BACKGROUND: The aim of this prospective, double-blinded study in patients with aortic sclerosis was to determine whether a new calcification propensity measure in the serum could predict disease progression. METHODS: We included 129 consecutive patients with aortic sclerosis as assessed during a routine clinical echocardiographic exam. Clinical, echocardiographic, and serum laboratory parameters were collected, including a new blood test providing an overall measure of calcification propensity by monitoring the maturation time of calciprotein particles (T50 test). The echocardiographic exam was repeated after 1 year. Multiple regression analysis was performed to identify independent predictors of the annual increase of peak transvalvular Doppler velocity (∆vmax). Furthermore, the accuracy of the T50 test to detect patients with the most marked stenosis progression was assessed by receiver operating characteristic (ROC)-analysis. RESULTS: Mean age was 75 ± 9 years, 79% were men. The T50 was 271 ± 58 min. Overall, there was no significant stenosis progression between baseline and follow-up (∆vmax 3.8 ± 29.8 cm/s, p = ns). The T50 test was not found to be an independent linear predictor in multivariate testing. By ROC-analysis, however, a T50-value ≤ 242 min was able to significantly detect a ∆vmax above the 90th percentile (∆vmax ≥ 43 cm/s, AUC = 0.67, p = .04, Sensitivity = 69%, Specificity = 70%). CONCLUSIONS: The T50 test showed a modest but significant ability to identify a pronounced aortic stenosis progression in patients with aortic sclerosis. The test could not be established as an independent linear predictor of disease progression, possibly due to the low valvular disease burden and short follow-up interval.

Sigmoid isostiffness-lines: An in-vitro model for the assessment of aortic stenosis severity.

Introduction: The aortic valve opening area (AVA), used to quantify aortic stenosis severity, depends on the transvalvular flow rate (Q). The currently accepted clinical echocardiographic method assumes a linear relation between AVA and Q. We studied whether a sigmoid model better describes this relation and determined "isostiffness-lines" across a wide flow spectrum, thus allowing building a nomogram for the non-invasive estimation of valve stiffness. Methods: Both AVA and instantaneous Q (Qinst) were measured at 10 different mean cardiac outputs of porcine aortic valves mounted in a pulsatile flow loop. The valves' cusps were chemically stiffened to obtain three stiffness grades and the procedure was repeated for each grade. The relative stiffness was defined as the ratio between LV work at grade with the added stiffness and at native stiffness grade. AVA peak ¯ corresponding to the selected Q peak ¯ of the highest 3 and 5 cardiac output values was predicted in K-fold cross-validation using sequentially a linear and a sigmoid model. The accuracy of each model was assessed with the Akaike information criterion (AIC). Results: The sigmoid model predicted more accurately AVA peak ¯ (AIC for prediction of AVA with Q peak ¯ of the 3 highest cardiac output values: -1,743 vs. -1,048; 5 highest cardiac output values: -1,471 vs. -878) than the linear model. Conclusion: This study suggests that the relation between AVA and Q can be better described by a sigmoid than a linear model. This construction of "isostiffness-lines" may be a useful method for the assessment of aortic stenosis in clinical echocardiography.

Algorithm for real-time analysis of intracoronary electrocardiogram.

Introduction: Since its first implementation in 1985, intracoronary (ic) electrocardiogram (ECG) has shown ample evidence for its diagnostic value given the higher sensitivity for myocardial ischemia detection in comparison to surface ECG. However, a lack of online systems to quantitatively analyze icECG in real-time prevents its routine use. The present study aimed to develop and validate an autonomous icECG analyzing algorithm. Materials and methods: This is a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a 1-min proximal coronary balloon occlusion was available. An ECG expert as well as the newly developed algorithm for autonomous icECG analysis measured the icECG ST-segment shift in mV for each icECG tracing. Results: Intraclass correlation coefficient (ICC) demonstrated low variability between the two methods (ICC = 0.968). Using the time point of icECG recording as allocation reference for absent or present myocardial ischemia, ROC-analysis for ischemia detection by the manually determined icECG ST-segment shift showed an area under the curve (AUC) of 0.968 ± 0.021 (p < 0.0001). AUC for the algorithm analysis was 0.967 ± 0.023 (p < 0.0001; p = 0.925 for the difference between the ROC curve AUCs). Time to complete analysis was below 1,000 ms for the autonomous icECG analysis and above 5 min for manual analysis. Conclusion: A newly developed autonomous icECG analysing algorithm detects myocardial ischemia with equal accuracy as manual ST-segment shift assessment. The algorithm provides the technical fundament for an analysing system to quantitatively obtain icECG in real-time.

Passive Leg Raise Stress Echocardiography in Severe Paradoxical Low-Flow, Low-Gradient Aortic Stenosis.

BACKGROUND: Dobutamine stress echocardiography is used to increase transvalvular flow in patients with low-flow, low-gradient aortic stenosis (AS). Dobutamine fails to increase the stroke volume index (SVI) in one third of patients. The aim of this study was to test whether passive leg raise (PLR) added to dobutamine could increase SVI and transvalvular flow in patients with severe paradoxical low-flow, low-gradient AS. METHODS: Forty-five patients with apparent severe low-flow, low-gradient AS on the basis of traditional measurements were included. Twenty-five were categorized as belonging to the paradox group (left ventricular ejection fraction [EF] ≥ 50%) and 20 to the low EF group (left ventricular EF < 50% or "classical" low-flow, low-gradient AS) for comparison. A four-step stress echocardiographic examination was performed: resting conditions (rest), PLR alone (PLR), maximal dobutamine infusion rate (Dmax), and a combination of Dmax and PLR (Dmax+PLR). Aortic valve area, SVI, and mean transvalvular flow were calculated using both the velocity-time integral (VTI) of left ventricular outflow tract and the Simpson method. Changes compared with rest and between the stress maneuvers were analyzed. RESULTS: In the paradox group, compared with rest, left ventricular end-diastolic volume was significantly decreased with Dmax but was completely restored with Dmax+PLR (rest vs Dmax vs Dmax+PLR: 61 ± 15 vs 49 ± 18 mL [P < .001] vs 61 ± 18 mL [P = NS]). The smallest increase in SVI in the paradox group was observed during Dmax (PLR vs Dmax vs Dmax+PLR: VTI, 38 ± 4 mL/m2 [P < .001] vs 36 ± 7 mL/m2 [P = .019] vs 41 ± 7 mL/m2 [P < .001]; Simpson, 28 ± 6 mL/m2 [P < .001], 21 ± 7 mL/m2 [P = NS], 27 ± 7 mL/m2 [P = NS]). Compared with Dmax, Dmax+PLR was able to achieve a higher SVI (VTI, 36 ± 7 vs 41 ± 7 mL/m2 [P < .001]; Simpson, 21 ± 7 vs 27 ± 7 mL/m2 [P < .001]) and transvalvular flow with the Simpson method only (179 ± 56 vs 219 ± 56 mL/sec, P < .001), as well as a higher mean gradient (34 ± 10 vs 39 ± 12 mm Hg, P = .003) and AVA with the Simpson method (0.64 ± 0.21 vs 0.73 ± 0.21 cm2, P = .026). In the low EF group, only SVI VTI (31 ± 8 vs 35 ± 7 mL/m2, P = .034) and mean gradient (29 ± 12 vs 34 ± 14 mm Hg, P = .003) were higher with Dmax+PLR. The proportion of patients with SVI VTI ≥ 35 mL/m2 and increases of SVI VTI of >20% compared with rest was highest with Dmax+PLR in both groups. CONCLUSIONS: Dobutamine decreases preload in paradoxical low-flow, low-gradient AS. Adding PLR counteracts this effect, resulting in increased SVI and flow (in one method). The combined stress maneuver allowed reclassification of some patients from severe to moderate AS and may therefore be useful in selected cases in this population in which severity is uncertain.

Yield of Echocardiography in Ischemic Stroke and Patients With Transient Ischemic Attack With Established Indications for Long-Term Direct Oral Anticoagulant Therapy: A Cross-Sectional Diagnostic Cohort Study.

Background We aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event. Methods and Results This was a retrospective cohort study of consecutive patients with preceding established indications for long-term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management-relevant high-risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence-based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70-84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1-12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1-3) days. TTE identified 26 of 191 (14%) patients with 35 management-relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management-relevant pathologies. Most management-relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management-relevant high-risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], C-reactive protein, d-dimer, and troponin levels). Conclusions In patients with established indications for long-term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management-relevant high-risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.

Association of Palmar Arch Collateral Function and Radial Artery Occlusion After Transradial Access.

The prevalence and implications of radial artery occlusion (RAO) after transradial catheterization are an intensely discussed topic, resulting in numerous preventive strategies such as adjusted anticoagulation, residual-patency hemostasis, or distal puncture site. The present study aimed at assessing an association of palmar arch, in particular radial artery collateral function and RAO after transradial access (TRA) catheterization. Radial artery collateral function was determined using radial artery pressure signals in the nonobstructed vessel and during brief manual occlusion of the more proximal radial artery. Collateral flow index, the ratio of mean occlusive divided by mean nonocclusive arterial blood pressure, both subtracted by central venous pressure, was determined during manual RAO (radial artery collateral flow index [CFIrad]). The presence or absence of RAO was determined by Doppler ultrasound at least 3 months after TRA. A total of 630 patients with TRA coronary angiography underwent palmar arch, that is, radial and radial plus ulnar artery collateral function assessment. CFIrad was equal to 0.808 ± 0.144 (95% confidence interval 0.797 to 0.819). A total of 200 patients underwent Doppler ultrasound examination of their forearm arterial circulation 301 ± 140 days after TRA. Eight (4%) patients showed signs of RAO, 4 of whom (2%) had a complete RAO and 4 (2%) a stenosis above 30%. Patients with RAO showed a higher CFIrad than those without RAO: 0.900 ± 0.074 versus 0.801 ± 0.154 (p = 0.006). In conclusion, complete RAO as determined by Doppler ultrasound later than 3 months after TRA is rare (2%). In the long run, RAO appears to be related to a very well-developed radial artery collateral function.

Anatomical and Technical Predictors of Three-Dimensional Mitral Valve Area Reduction After Transcatheter Edge-To-Edge Repair.

BACKGROUND: Among current transcatheter therapies for the treatment of mitral regurgitation, the MitraClip (MC; Abbott Vascular, Abbott Park, IL) system is the most commonly used. MitraClip implantation is usually contraindicated in patients with a mitral valve area (MVA) < 4.0 cm2. However, little is known about the real impact of MC implantation on MVA. Our goal was to investigate the factors influencing MVA reduction and derive the minimal MVA required to prevent the development of a clinically significant mitral stenosis (MVA < 1.5 cm2) in different clinical scenarios. METHODS: Using three-dimensional data sets, the annulus and leaflet anatomy and MVA before clip implantation (MVABC) were assessed. After each MC implant (NTR or XTR), the relative MVA reduction and the absolute residual MVA were measured and their predictors evaluated. RESULTS: The present analysis included 116 patients. An MC XTR was the first device implanted in 50% of the subjects, and 53% were treated with a single implant. The MVA reduction following one XTR was 57% ± 7% versus 52% ± 8% after one NTR (P = .001). A lower MVA reduction was observed when the MC was placed commissural/central versus paracentral (50% ± 8% vs 57% ± 7%, P < .0001). After a second device, the additional MVA reduction was higher when creating a triple-compared with a double-orifice morphology (34% ± 11% vs 25% ± 9%, P = .001). The MVA after one MC correlated with MVABC as well as with the clip type and position (r = 0.91, P < .0001). The MVABC, orifice morphology, and first device position predicted MVA after two implants (r = 0.82, P < .0001). Based on the mathematical relationship between these parameters, the minimal MVABC needed in eight different clinical scenarios was summarized in a decision algorithm: the values ranged from 3.5 to 4.7 cm2 for one and 4.5 to 6.3 cm2 for two MC strategies. CONCLUSIONS: The minimal native MVA preventing clinically relevant MS after transcatheter edge-to-edge repair is predicted by the number and location of clip(s), orifice morphology, and device type. Based on these parameters, an algorithm has been derived to optimize patient selection and preprocedural planning.

Preparation of artificial vascularised tissue and the indirect determination of its void volume using µCT.

The non-invasive determination of the vasculature volume would be very useful in many fields of medicine such as oncology and implantation. The purpose of this research was, therefore, to develop a methodology to investigate vascularisation in phantoms using microcomputed tomography (µCT) without having to visualise the single vessels. Epoxy resin and cotton candy were used to form the phantoms with microchannels. The size of the channels was measured via microscopy and the proportion of the void volume (PVV) was calculated. The phantoms were placed in contrast agent solutions of different concentrations and scanned in µCT. The mean CT numbers of the phantoms were calculated with the Amira software and displayed as a function of the determined PVV and the contrast agent concentration (CAC). The fabricated microchannels had the size of biological capillaries (diameter: 5 µm to 15 µm) and the phantoms showed a microchannel density of 5 to15 microchannels per mm². With an increasing CAC, the CT numbers increased significantly. Additionally, the phantoms with a higher PVV also had a higher CT number. The CT numbers and the PVV correlated moderately together, but significantly. The slope of the regression line increased with an increasing CAC.

Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis.

BACKGROUND: Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete. OBJECTIVES: To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis. SEARCH METHODS: We identified studies through systematic searches of the following bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); and Embase from January 1947 to December 2020. In addition, we checked trial registries for ongoing or unpublished eligible trials and manually searched for abstracts from scientific and clinical meetings. SELECTION CRITERIA: We evaluated randomised controlled trials (RCTs) comparing two or more therapies in people with NETs (primarily gastrointestinal and pancreatic). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data to a pre-designed data extraction form. Multi-arm studies were included in the network meta-analysis using the R-package netmeta. We separately analysed two different outcomes (disease control and progression-free survival) and two types of NET (gastrointestinal and pancreatic NET) in four network meta-analyses. A frequentist approach was used to compare the efficacy of therapies. MAIN RESULTS: We identified 55 studies in 90 records in the qualitative analysis, reporting 39 primary RCTs and 16 subgroup analyses. We included 22 RCTs, with 4299 participants, that reported disease control and/or progression-free survival in the network meta-analysis. Precision-of-treatment estimates and estimated heterogeneity were limited, although the risk of bias was predominantly low. The network meta-analysis of progression-free survival found nine therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.36 [95% CI, 0.28 to 0.46]), interferon plus somatostatin analogue (HR, 0.34 [95% CI, 0.14 to 0.80]), everolimus plus somatostatin analogue (HR, 0.38 [95% CI, 0.26 to 0.57]), bevacizumab plus somatostatin analogue (HR, 0.36 [95% CI, 0.15 to 0.89]), interferon (HR, 0.41 [95% CI, 0.18 to 0.94]), sunitinib (HR, 0.42 [95% CI, 0.26 to 0.67]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.48 [95% CI, 0.28 to 0.83]), surufatinib (HR, 0.49 [95% CI, 0.32 to 0.76]), and somatostatin analogue (HR, 0.51 [95% CI, 0.34 to 0.77]); and six therapies for gastrointestinal NETs: 177-Lu-DOTATATE plus somatostatin analogue (HR, 0.07 [95% CI, 0.02 to 0.26]), everolimus plus somatostatin analogue (HR, 0.12 [95%CI, 0.03 to 0.54]), bevacizumab plus somatostatin analogue (HR, 0.18 [95% CI, 0.04 to 0.94]), interferon plus somatostatin analogue (HR, 0.23 [95% CI, 0.06 to 0.93]), surufatinib (HR, 0.33 [95%CI, 0.12 to 0.88]), and somatostatin analogue (HR, 0.34 [95% CI, 0.16 to 0.76]), with higher efficacy than placebo. Besides everolimus for pancreatic NETs, the results suggested an overall superiority of combination therapies, including somatostatin analogues. The results indicate that NET therapies have a broad range of risk for adverse events and effects on quality of life, but these were reported inconsistently. Evidence from this network meta-analysis (and underlying RCTs) does not support any particular therapy (or combinations of therapies) with respect to patient-centred outcomes (e.g. overall survival and quality of life). AUTHORS' CONCLUSIONS: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.

Cardiovascular MRI Compared to Echocardiography to Identify Cardioaortic Sources of Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: To compare the diagnostic yield of echocardiography and cardiovascular MRI (CMR) to detect structural sources of embolism, in patients with ischemic stroke with a secondary analysis of non-stroke populations. Methods and Results: We searched MEDLINE/Embase (from 01.01.2000 to 24.04.2021) for studies including CMR to assess prespecified sources of embolism. Comparison included transthoracic and/or transesophageal echocardiography. Two authors independently screened studies, extracted data and assessed bias using the QUADAS-2 tool. Estimates of diagnostic yield were reported and pooled. Twenty-seven studies with 2,525 patients were included in a study-level analysis. Most studies had moderate to high risk of bias. Persistent foramen ovale, complex aortic plaques, left ventricular and left atrial thrombus were the most common pathologies. There was no difference in the yield of left ventricular thrombus detection between both modalities for stroke populations (4 studies), but an increased yield of CMR in non-stroke populations (28.1 vs. 16.0%, P < 0.001, 10 studies). The diagnostic yield in stroke patients for detection of persistent foramen ovale was lower in CMR compared to transoesophageal echocardiography (29.3 vs. 53.7%, P < 0.001, 5 studies). For both echocardiography and CMR the clinical impact of the management consequences derived from many of the diagnostic findings remained undetermined in the identified studies. Conclusions: Echocardiography and CMR seem to have similar diagnostic yield for most cardioaortic sources of embolism except persistent foramen ovale and left ventricular thrombus. Randomized controlled diagnostic trials are necessary to understand the impact on the management and potential clinical benefits of the assessment of structural cardioaortic stroke sources. Registration: PROSPERO: CRD42020158787.

Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis.

Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this beneficial functional connection is invertible and can be linked to coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. This was an observational study including 40 patients with chronic coronary syndrome, distal IMA occlusion, and upper limb hyperemia (verum group), and 40 propensity score matched controls (placebo group) without IMA occlusion or hyperemia. Primary study end point was the intergroup difference and temporal development in coronary collateral function (i.e., collateral flow index; CFI) as obtained at 30, 45, and 60 s following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-min suprasystolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Between the first and the second CFI measurement, CFI change (i.e., CFI@45s - CFI@30s) was absent in the verum group whereas there was CFI recruitment in the placebo group: 0.000 ± 0.023 and +0.009 ± 0.013, respectively; P = 0.032. Among patients with artificial distal IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia.NEW & NOTEWORTHY Induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal among patients with artificial distal internal mammary artery occlusion. Coronary steal via the occluded internal mammary arteries serves as alternate proof of concept of the already existing evidence of their functional extracoronary collateral supply.

Detection of myocardial ischemia by intracoronary ECG using convolutional neural networks.

INTRODUCTION: The electrocardiogram (ECG) is a valuable tool for the diagnosis of myocardial ischemia as it presents distinctive ischemic patterns. Deep learning methods such as convolutional neural networks (CNN) are employed to extract data-derived features and to recognize natural patterns. Hence, CNN enable an unbiased view on well-known clinical phenomenon, e.g., myocardial ischemia. This study tested a novel, hypothesis-generating approach using pre-trained CNN to determine the optimal ischemic parameter as obtained from the highly susceptible intracoronary ECG (icECG). METHOD: This was a retrospective observational study in 228 patients with chronic coronary syndrome. Each patient had participated in clinical trials with icECG recording and ST-segment shift measurement at the beginning (i.e., non-ischemic) and the end (i.e., ischemic) of a one-minute proximal coronary artery balloon occlusion establishing the reference. Using these data (893 icECGs in total), two pre-trained, open-access CNN (GoogLeNet/ResNet101) were trained to recognize ischemia. The best performing CNN during training were compared with the icECG ST-segment shift for diagnostic accuracy in the detection of artificially induced myocardial ischemia. RESULTS: Using coronary patency or occlusion as reference for absent or present myocardial ischemia, receiver-operating-characteristics (ROC)-analysis of manually obtained icECG ST-segment shift (mV) showed an area under the ROC-curve (AUC) of 0.903±0.043 (p<0.0001, sensitivity 80%, specificity 92% at a cut-off of 0.279mV). The best performing CNN showed an AUC of 0.924 (sensitivity 93%, specificity 92%). DeLong-Test of the ROC-curves showed no significant difference between the AUCs. The underlying morphology responsible for the network prediction differed between the trained networks but was focused on the ST-segment and the T-wave for myocardial ischemia detection. CONCLUSIONS: When tested in an experimental setting with artificially induced coronary artery occlusion, quantitative icECG ST-segment shift and CNN using pathophysiologic prediction criteria detect myocardial ischemia with similarly high accuracy.

Postoperative wound assessment in cattle: How reliable is the back hand palpation?

BACKGROUND: As part of clinical wound assessment in bovine surgery, discrepancies in skin temperature are evaluated by placing the back of the hand on the area to be examined. Generally, an increased skin temperature at the wound site for a prolonged period is considered as an indicator of impaired wound healing. The aim of this study was to verify the reliability of palpation under bovine practice conditions using laparotomy as an example. Fourteen cows (German Holstein) with a left displacement of the abomasum (LDA) without other severe concurrent diseases were examined preoperatively and once daily for ten days after surgery. The skin temperature of the wound site in the right flank was assessed by palpation, followed by thermographic evaluation using an infrared camera after a 45-min acclimatisation period, under standardised conditions in a closed examination room daily for 10 days. RESULTS: All the incisions healed without clinical detectable perturbances. The ambient temperature range during the study period was 7.8 - 24.1 °C. Two groups were retrospectively defined according to the ambient temperature: high ambient temperature (HT group; median: 20.2 °C 25/75 quartile: 18.5 °C / 21.7 °C; n = 6) and low ambient temperature (LT group; 10.8 °C; 9.4 °C / 12.8 °C; n = 8). The temperature differences (Δϑ) between the mean skin temperature of the wound site and a defined reference area cranial to the wound were assessed. A significant negative correlation was found between the ambient temperature (ϑAmb) and Δϑ (r=-0.51; P < 0.001). The Δϑ was postoperatively higher in the cows in the LT group (median of the individual animals 0.8-2.5 °C) than in the HT group (0.1-0.5 °C; P < 0.05). In contrast to the thermographic findings, manual palpation rarely detected local hyperthermia (> 1 °C) at the wound site (sensitivity 0.20; specificity 0.96). CONCLUSIONS: The infrared thermography provides a more reliable assessment of temperature changes at the wound site in comparison to manual palpation. The ambient temperature markedly affects the extent of local hyperthermia at the wound site.