Impact of left atrial wall motion assumptions in fluid simulations on proposed predictors of thrombus formation.

Atrial fibrillation (AF) poses a significant risk of stroke due to thrombus formation, which primarily occurs in the left atrial appendage (LAA). Medical image-based computational fluid dynamics (CFD) simulations can provide valuable insight into patient-specific hemodynamics and could potentially enhance personalized assessment of thrombus risk. However, the importance of accurately representing the left atrial (LA) wall dynamics has not been fully resolved. In this study, we compared four modeling scenarios; rigid walls, a generic wall motion based on a reference motion, a semi-generic wall motion based on patient-specific motion, and patient-specific wall motion based on medical images. We considered a LA geometry acquired from 4D computed tomography during AF, systematically performed convergence tests to assess the numerical accuracy of our solution strategy, and quantified the differences between the four approaches. The results revealed that wall motion had no discernible impact on LA cavity hemodynamics, nor on the markers that indicate thrombus formation. However, the flow patterns within the LAA deviated significantly in the rigid model, indicating that the assumption of rigid walls may lead to errors in the estimated risk factors. In contrast, the generic, semi-generic, and patient-specific cases were qualitatively similar. The results highlight the crucial role of wall motion on hemodynamics and predictors of thrombus formation, and also demonstrate the potential of using a generic motion model as a surrogate for the more complex patient-specific motion. While the present study considered a single case, the employed CFD framework is entirely open-source and designed for adaptability, allowing for integration of additional models and generic motions.

Regression of Cardiac Lymphoma With Chemotherapy.

A patient was admitted for chest pain with electrocardiographic changes, and cardiac magnetic resonance showed focal myocardial hypertrophy secondary to edema. Combined positron emission tomography and computed tomography corroborated foci of myocardial hypermetabolism, as well as multiple adenopathies consistent with lymphoma in the biopsy. Hypertrophy and edema regressed with chemotherapy.

Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention. METHODS: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality. RESULTS: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%). CONCLUSION: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018).

Usefulness of Cardiac Computed Tomography in Coronary Risk Prediction: A Five-Year Follow-Up of the SPICA Study (Secure Prevention with Imaging of the Coronary Arteries).

Accurate identification of individuals at high coronary risk would reduce acute coronary syndrome incidence and morbi-mortality. We analyzed the effect on coronary risk prediction of adding coronary artery calcification (CAC) and Segment Involvement Score (SIS) to cardiovascular risk factors. This was a prospective cohort study of asymptomatic patients recruited between 2013-2017. All participants underwent a coronary computed tomography angiography to determine CAC and SIS. The cohort was followed-up for a composite endpoint of myocardial infarction, coronary angiography and/or revascularization (median = five years). Discrimination and reclassification of the REGICOR function with CAC/SIS were examined with the Sommer's D index and with the Net reclassification index (NRI). Nine of the 251 individuals included had an event. Of the included participants, 94 had a CAC = 0 and 85 a SIS = 0, none of them had an event. The addition of SIS or of SIS and CAC to the REGICOR risk function significantly increased the discrimination capacity from 0.74 to 0.89. Reclassification improved significantly when SIS or both scores were included. CAC and SIS were associated with five-year coronary event incidence, independently of cardiovascular risk factors. Discrimination and reclassification of the REGICOR risk function were significantly improved by both indexes, but SIS overrode the effect of CAC.

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses.

Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimized codons show high expression levels at the first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time, allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimization of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.

Stem endophytes increase root development, photosynthesis, and survival of elm plantlets (Ulmus minor Mill.).

Long-lived trees benefit from fungal symbiotic interactions in the adaptation to constantly changing environments. Previous studies revealed a core fungal endobiome in Ulmus minor which has been suggested to play a critical role in plant functioning. Here, we hypothesized that these core endophytes are involved in abiotic stress tolerance. To test this hypothesis, two core endophytes (Cystobasidiales and Chaetothyriales) were inoculated into in vitro U. minor plantlets, which were further subjected to drought. Given that elm genotypes resistant to Dutch elm disease (DED) tend to show higher abiotic stress tolerance than susceptible ones, we tested the endophyte effect on two DED-resistant and two DED-susceptible genotypes. Drought stress was moderate; endophyte presence attenuated stomata closure in response to drought in one genotype but this stress did not affect plant survival. In comparison, long-term in-vitro culture proved stressful to mock-inoculated plants, especially in DED-susceptible genotypes. Interestingly, no endophyte-inoculated plant died during the experiment, as compared to high mortality in mock-inoculated plants. In surviving plants, endophyte presence stimulated root and shoot growth, photosynthetic rates, antioxidant activity and molecular changes involving auxin-signaling. These changes and the observed endophyte stability in elm tissues throughout the experiment suggest endophytes are potential tools to improve survival and stress tolerance of DED-resistant elms in elm restoration programs.

The influence of surgeons and technicians on the learning curve of femtosecond-laser cataract surgery.

PURPOSE: To demonstrate the influence of the surgeon's and the operating room (OR) technicians' experience upon the outcome of femtosecond laser-assisted cataract surgery (FLACS). MATERIALS AND METHODS: Our study included 250 eyes from 156 patients who had undergone either cataract surgery or clear-crystalline-lens extraction and where capsulorhexis and lens fragmentation had been performed using the CATALYS® Precision System femtosecond platform (Abbott Medical Optics Inc., Santa Ana, CA, USA).The patients were operated either by an experienced surgeon in the use of femtosecond laser or by an inexperienced surgeon in that field and two technicians. The quantitative outcome measures were: Suction loss rate, vacuum time, number of consumables used by the patient and intraoperative complication rate. RESULTS: Both for the experienced and the inexperienced surgeons, suction loss rates as well as vacuum time decreased progressively as time went by and more surgical procedures had been completed by that surgeon. For a given surgeon suction time decreased significantly, going from 137 to 99s, as the assisting technician gradually gained experience. The number of consumables used in each procedure by the experienced surgeon ranged from 1.10 (for the first 50 cases) to 1.02 from those initial cases onwards. Regarding intraoperative complications, they also decreased progressively as the number of procedures completed by the surgeon increased. CONCLUSIONS: The experience of each team member involved in such procedures-be it surgeons or technicians-have an impact, to a greater or lesser extent, upon the surgery's outcome, as quantified by the outcome variables of choice.

An Exceptional Cause of Acute Right Heart Failure: Isolated Right Ventricular Takotsubo Syndrome.

We describe a patient with of acute right ventricular dysfunction secondary to right ventricular isolated Takotsubo syndrome (TTS). The importance of appropriate differential diagnosis for acute right ventricular dysfunction differential diagnosis of acute right ventricular dysfunction and the differences in diagnosis and management of right ventricular TTS and typical left ventricular TTS are highlighted. (Level of Difficulty: Intermediate.).

Growth resilience and oxidative burst control as tolerance factors to Ophiostoma novo-ulmi in Ulmus minor.

The Dutch elm disease (DED) pathogens, Ophiostoma ulmi (Buisman) Nannf. and the more aggressive Ophiostoma novo-ulmi Brasier, have decimated European elm populations in the last 100 years. Today, the number of tolerant elm varieties available on the market is limited, partly due to the long breeding cycles and expensive facilities they require. Developing a low-cost technique to allow early screening of elm tolerance based on simple morphological and/or biochemical traits would considerably boost elm breeding and research. Within this general aim, we developed an in vitro plant culture system to (i) characterize stress responses to O. novo-ulmi-root inoculation in two Ulmus minor Mill. clones of contrasting susceptibility level to DED (termed 'tolerant' and 'susceptible') and (ii) compare the upward dispersal rate of the pathogen in the two clones. Constitutive xylem anatomy was similar in both clones, indicating that differences in plant responses to the pathogen are not attributable to anatomical factors (e.g., conduit size). Susceptible plantlets suffered a significant delay in apical growth and a decrease in chlorophyll content at 21 days post-inoculation (dpi). The rate of pathogen dispersal from roots to aerial tissues was similar in both clones. However, the tolerant clone showed a marked increase in lipid peroxidation at 1 dpi, while the susceptible clone showed enhanced values of lipid peroxidation during most of the experimental period (1-21 dpi). Despite wide stem colonization by the pathogen, the tolerant clone effectively regulated the oxidative stress levels and showed remarkable resilience to inoculation. These results extend current knowledge on elm defense mechanisms, and the proposed in vitro plant culture system emerges as a promising early screening method for tolerance to improve elm breeding.

Subtraction CT angiography improves evaluation of significant coronary artery disease in patients with severe calcifications or stents-the C-Sub 320 multicenter trial.

OBJECTIVES: Diagnostic accuracy of conventional coronary CT angiography (CCTAconv) may be compromised by blooming artifacts from calcifications or stents. Blooming artifacts may be reduced by subtraction coronary CT angiography (CCTAsub) in which non-contrast and contrast CT data sets are subtracted digitally. We tested whether CCTAsub in patients with severe coronary calcification or stents reduces the number of false-positive stenosis evaluations compared with CCTAconv. METHODS: In this study, 180 symptomatic patients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and CT scanned (2013-2016) at three international centers. CCTAconv, and CCTAsub data sets were reconstructed. Target segments were defined as motion-free coronary segments with a suspected stenosis (> 50% of lumen) potentially due to blooming of either calcium or stents. Target segments were evaluated with respect to misregistration artifacts from the CCTAsub reconstruction process, in which case evaluation was omitted. CCTAsub and CCTAconv were compared with ICA. Primary outcome measure was the frequency of false positives by CCTAconv versus CCTAsub to identify > 50% coronary stenosis by ICA on a per-segment level. RESULTS: After exclusion of 76 patients, 104 (14% females) with mean age 67 years and median Agatston score 852 were included. There were 136 target segments with misregistration and 121 target segments without. Accuracy calculations in target segments without misregistration showed a reduction of the false positives from 72% [95% confidence interval (CI): 63-80%] in CCTAconv to 33% (CI:25-42%) in CCTAsub, at the expense of 7% (CI:3-14%) false negatives in CCTAsub. CONCLUSIONS: In severely calcified coronary arteries or stents, CCTAsub reduces the false-positive rate in well-aligned, calcified or stent segments suspected of significant stenosis on CCTAconv. Nevertheless, misregistration artifacts are frequent in CCTAsub. KEY POINTS: • A high calcium-score reduces the diagnostic accuracy in patients scanned with cardiac CT. • These patients would normally need an invasive angiogram for diagnosis. • In this prospective, multicenter study, subtraction CT, when evaluable, reduces false-positive stenosis evaluations. • Subtraction coronary CT angiography may, when evaluable, reduce excessive downstream testing.

Further insights into the components of resistance to Ophiostoma novo-ulmi in Ulmus minor: hydraulic conductance, stomatal sensitivity and bark dehydration.

Dutch elm disease (DED) is a vascular disease that has killed over 1 billion elm trees. The pathogen spreads throughout the xylem network triggering vessel blockage, which results in water stress, tissue dehydration and extensive leaf wilting in susceptible genotypes. We investigated the differences between four Ulmus minor Mill. clones of contrasting susceptibility to Ophiostoma novo-ulmi Brasier regarding morphological, anatomical and physiological traits affecting water transport, in order to gain a better understanding of the mechanisms underlying DED susceptibility. We analyzed the differential response to water shortage and increased air vapor pressure deficit (VPD) to investigate whether resistance to water stress might be related to DED tolerance. Sixteen plants per clone, aged 2 years, were grown inside a greenhouse under differential watering. Stomatal conductance was measured under ambient and increased VPD. Growth, bark water content and stem hydraulic and anatomical parameters were measured 22 days after starting differential watering. Vessel lumen area, lumen fraction and hydraulic conductance were highest in susceptible clones. Stomatal conductance was lowest under low VPD and decreased faster under increased VPD in resistant clones. We found a negative relationship between the decrease in stomatal conductance at increased VPD and specific hydraulic conductance, revealing a narrower hydraulic margin for sustaining transpiration in resistant clones. The effect of water shortage was greater on radial stem growth than on leaf area, which could be explained through an extensive use of capacitance water to buffer xylem water potential. Water shortage reduced stomatal conductance and vessel lumen area. Bark water content under conditions of water shortage only decreased in susceptible clones. Higher hydraulic constraints to sap flow in resistant clones may determine higher stomatal sensitivity to VPD and so contribute to DED resistance by limiting pathogen expansion and reducing water loss and metabolic impairment in cells involved in fighting against infection.

Reliability of a new method for coronary artery calcium or metal subtraction by 320-row cardiac CT.

PURPOSE: To investigate the feasibility and diagnostic accuracy of subtraction CTA on patients with highly calcified coronary artery disease (CAD) or previous implanted stents, in comparison with invasive coronary angiography (ICA). MATERIALS AND METHODS: Twenty-three patients were recruited. All conventional and subtraction CTA exams were performed using a 320-row CT. Subjective image quality score was assessed for each segment using a 4-point scale: 1-uninterpretable to 4-good image quality. RESULTS: A total of 129 calcified or stented coronary segments were studied. Mean coronary image quality with conventional CTA was 2.73 ± 0.97 and in subtracted CTA 3.3 ± 0.92 (p < 0.01). After metal subtraction, image quality in stented coronary segments with >3 mm of diameter improved from 2.69 ± 0.97 to 3.34 ± 0.89 (p = 0.01) and in those with <3 mm of diameter from 2.11 ± 0.78 to 2.67 ± 0.87 (p = 0.17). There was an improvement in diagnostic accuracy to detect ICA stenosis >50 % by subtraction CTA compared with conventional CTA (AUC 0.93 to 0.87; p = 0.02). CONCLUSION: Subtraction CTA is promising in overcoming limitations of conventional CTA due to calcium or metal artefacts, especially if no motion artefact is present or when stents > 3 mm are studied. KEY POINTS: • Calcium and metal artefacts are still a limitation for conventional coronary CTA • Diagnostic accuracy is improved by subtraction as compared with conventional CTA • Subtraction CTA is a promising tool to overcome limitations of conventional CTA.

Coronary computed tomographic angiographic findings in asymptomatic patients with heterozygous familial hypercholesterolemia and null allele low-density lipoprotein receptor mutations.

Heterozygous familial hypercholesterolemia (HeFH) can be associated with early coronary artery disease (CAD) in asymptomatic patients. The objectives of the present study were to assess the prevalence and magnitude of subclinical CAD in patients with HeFH using coronary computed tomographic angiography (CCTA) and to determine the clinical and genetic profile of those at the greatest risk of CAD. The study included 50 consecutive patients with HeFH diagnosed according to the Dutch Lipid Clinic Network criteria and a control group of 70 healthy subjects. The findings from CCTA for the patients with HeFH were compared with those from the control group, who had been referred for CCTA as a part of a preventive medical examination. In 82% of the patients with HeFH, genetic DNA was screened for low-density lipoprotein receptor (LDLR) gene mutations using a microarray. CCTA revealed a significantly greater Agatston calcium score in the study group than in the control group (260 vs 46; p = 0.002). The prevalence of CAD in the patients with HeFH was 48%. It was significant in 26%, involving mainly the proximal segments of the coronary arteries. In the control group, the prevalence of CAD was 33% and was significant in 5% (p <0.05 for prevalence and severity of CAD compared to patients with HeFH). In those with HeFH, increased age, null allele LDLR mutations, and low high-density lipoprotein blood levels at diagnosis showed a statistically significant association with CAD (p <0.05). In conclusion, patients with HeFH present with a greater prevalence, extension, and severity of subclinical CAD than the general population. Increased age, low high-density lipoprotein levels, and LDLR null allele mutations are related to the occurrence of CAD. CCTA has emerged as a useful technique for the screening of subclinical CAD in patients with HeFH.