Artificial Intelligence Interpretation of the Electrocardiogram: A State-of-the-Art Review.

PURPOSE OF REVIEW: Artificial intelligence (AI) is transforming electrocardiography (ECG) interpretation. AI diagnostics can reach beyond human capabilities, facilitate automated access to nuanced ECG interpretation, and expand the scope of cardiovascular screening in the population. AI can be applied to the standard 12-lead resting ECG and single-lead ECGs in external monitors, implantable devices, and direct-to-consumer smart devices. We summarize the current state of the literature on AI-ECG. RECENT FINDINGS: Rhythm classification was the first application of AI-ECG. Subsequently, AI-ECG models have been developed for screening structural heart disease including hypertrophic cardiomyopathy, cardiac amyloidosis, aortic stenosis, pulmonary hypertension, and left ventricular systolic dysfunction. Further, AI models can predict future events like development of systolic heart failure and atrial fibrillation. AI-ECG exhibits potential in acute cardiac events and non-cardiac applications, including acute pulmonary embolism, electrolyte abnormalities, monitoring drugs therapy, sleep apnea, and predicting all-cause mortality. Many AI models in the domain of cardiac monitors and smart watches have received Food and Drug Administration (FDA) clearance for rhythm classification, while others for identification of cardiac amyloidosis, pulmonary hypertension and left ventricular dysfunction have received breakthrough device designation. As AI-ECG models continue to be developed, in addition to regulatory oversight and monetization challenges, thoughtful clinical implementation to streamline workflows, avoiding information overload and overwhelming of healthcare systems with false positive results is necessary. Research to demonstrate and validate improvement in healthcare efficiency and improved patient outcomes would be required before widespread adoption of any AI-ECG model.

Extracorporeal membrane oxygenation in paediatric cardiac surgery: 5-year single centre experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has become an integral part of paediatric cardiac surgery. We report the experience of a well-established ECMO service over 5 years. METHODS: This retrospective study analysed all paediatric patients who required ECMO support following cardiac surgery from April 2015 to March 2020. Inclusion criteria were age less than 18 years and post-operative ECMO support. Patients were analysed dividing into groups according to the urgency for ECMO support (extracorporeal cardiopulmonary resuscitation (ECPR) and cardiac ECMO) and according to age (neonatal and paediatric ECMO groups). They were followed for 30-day, 6-month mortality, long-term survival, postoperative morbidity and the need for reintervention. RESULTS: Forty-six patients were included who had a total of venoarterial (VA) 8 ECMO runs. The 5-year incidence of the need for VA ECMO after cardiac surgery was 3.3% (48 of the overall 1441 cases recorded). The median follow-up period was 3.5 (interquartile ranges, 0.8-4.7) years. Thirty-day, 6-month and follow-up survival rate was 85%, 65% and 52% respectively. At the 6-month follow-up, the ECPR group showed a trend towards worse survival compared with the cardiac ECMO group (47% vs. 55%) but with no statistical significance (p = 0.35). Furthermore, the survival rates between paediatric (60%) and neonatal (46%) ECMO groups were similar, with no statistical significance (p = 0.45). The rate of acute neurological events was 27% (13/48). CONCLUSION: ECPR and neonatal ECMO groups had higher mortality. VA ECMO 30-day and 6-month survival rates were 85% and 65% respectively. Major neurological injury resulting in ECMO termination occurred in 3 patients. Accumulated experiences and protocols in ECMO management can improve mortality and morbidity.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Development of and Gathering Validity Evidence for a Theoretical Test in Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is an imaging modality applied in a broad field of medical specialties for diagnostic uses, guidance during biopsy procedures and ablation therapies and sonoporation therapy. Appropriate training and assessment of theoretical and practical competencies are recommended before practicing CEUS, but no validated assessment tools exist. This study was aimed at developing a theoretical multiple-choice question-based test for core CEUS competencies and gathering validity evidence for the test. An expert team developed the test via a Delphi process. The test was administered to medical doctors with varying CEUS experience, and the results were used to evaluate test items, internal-consistency reliability, ability to distinguish between different proficiency levels and to establish a pass/fail score. Validity evidence was gathered according to Messick's framework. The final test with 47 test items could distinguish between operators with and without CEUS experience with acceptable reliability. The pass/fail score led to considerable risk of false positives and negatives. The test may be used as an entry test before learning practical CEUS competencies but is not recommended for certification purposes because of the risk of false positives and negatives.

Extra-Corporeal Membrane Oxygenation for Neonatal Respiratory Support.

To review our experience with Extra-Corporeal Membrane Oxygenation (ECMO) for respiratory support in neonates. From 1989 to 2018 2114 patients underwent respiratory ECMO support, with 764 (36%) neonates. Veno-Venous (V-V) cannulation was used in 428 (56%) neonates and Veno-Arterial (V-A) in 336 (44%). Historically V-V ECMO was our preferred modality, but due to lack of suitable cannula in the last 7 years V-A was used in 209/228 (92%) neonates. Mean and inter-quartile range of ECMO duration was 117 hours (inter-quartile range 90 to 164 hours). Overall 724 (95%) neonates survived to ECMO decannulation, with 640 (84%) hospital discharge. Survival varied with underlying diagnosis: meconium aspiration 98% (354/362), persistent pulmonary hypertension 80% (120/151), congenital diaphragmatic hernia 66% (82/124), sepsis 59% (35/59), pneumonia 86% (6/7), other 71% (43/61). Survival was 86% with V-V and 80% with V-A cannulation, better than ELSO Registry with 77% V-V and 63% V-A. Major complications: cerebral infarction/hemorrhage in 4.7% (31.1% survival to discharge), renal replacement therapy in 17.6% (58.1% survival to discharge), new infection in 2.9%, with negative impact on survival (30%). Following a circuit design modification and subsequent reduction in heparin requirement, intracerebral hemorrhage decreased to 9/299 (3.0%) radiologically proven cerebral infarction/hemorrhage. We concluded (1) outcomes from neonatal ECMO in our large case series were excellent, with better survival and lower complication rate than reported in ELSO registry. (2) These results highlight the benefits of ECMO service in high volume units. (3) The similar survival rate seen in neonates with V-A and V-V cannulation differs from the ELSO register; this may reflect the change in cannulation enforced by lack of suitable V-V cannula and all neonates undergoing V-A cannulation.

The use of extracorporeal membrane oxygenation in neonates with severe congenital diaphragmatic hernia: a 26-year experience from a tertiary centre.

OBJECTIVES: Neonates with severe congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation (ECMO) have a high rate of mortality. There is controversy regarding optimal time of surgical intervention. We present our data over a 26-year period. METHODS: We analysed data from our Extracorporeal Life Support Organization registry forms between 1989 and 2015, in order to determine the factors affecting survival outcome for repair of congenital diaphragmatic hernia with ECMO as a bridge to surgery and/or recovery. RESULTS: Ninety-eight neonates with congenital diaphragmatic hernia requiring ECMO were identified. In-hospital mortality was 32%. The overall mortality (47.9%) in our study was seen up to 7 months, after this point there was no mortality. There was no difference in survival in patients repaired using pre-, intra- or postoperative ECMO (P = 0.65). Requiring haemofiltration at any point was significantly associated with reduced survival [hazard ratio 2.7 (95% confidence interval 1.5-4.9); P = 0.01] as was the presence of neurological complications [hazard ratio 3.7 (95% confidence interval 1.6-8.5); P = 0.003]. Age, Apgar score, mode of delivery, side, associated cardiac comorbidities, pH, partial pressure of carbon dioxide, partial pressure of oxygen, oxygen saturations, bicarbonate, high-frequency oscillatory ventilation, mode of ECMO, inhaled nitric oxide, pulmonary complications and bleeding were not associated with any survival difference. CONCLUSIONS: We believe that all neonates with severe diaphragmatic hernia should be given the option of ECMO if clinically indicated. Provided these patients survive the initial postoperative period, they go on to have a sustained survival benefit. Long-term cost analysis and morbidity need to be taken into account to determine the true effect of ECMO on congenital diaphragmatic hernia.

Quantum Radiation Reaction: From Interference to Incoherence.

We investigate quantum radiation reaction in laser-electron interactions across different energy and intensity regimes. Using a fully quantum approach which also accounts exactly for the effect of the strong laser pulse on the electron motion, we identify in particular a regime in which radiation reaction is dominated by quantum interference. We find signatures of quantum radiation reaction in the electron spectra which have no classical analogue and which cannot be captured by the incoherent approximations typically used in the high-intensity regime. These signatures are measurable with presently available laser and accelerator technology.

Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys.

Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts.

Fiber-based solid phase microextraction using fused silica lined bottles to collect, store, and stabilize a multianalyte headspace gas sample for offline analyses.

We have developed a solid phase microextraction (SPME) sampling method using fused silica lined bottles (400 ml) to collect, store, and stabilize a headspace subsample from the source for subsequent offline, repetitive analyses of the gas using fiber-based SPME. The method enables long-term stability for repeated offline analysis of the organic species collected from the source headspace and retains all the advantages of fiber SPME sampling (e.g. rapid extraction, solvent free, simple and inexpensive) while providing additional advantages. Typically, the analytes collected on the SPME fiber must be desorbed and analyzed immediately to mitigate analyte loss or contamination. The new SPME sampling method, conducted offline using carboxen/polydimethylsiloxane (carboxen/PDMS - 85 µm) coated fibers, has been shown to be identical to in situ SPME sampling of a headspace acquired from an 80 component organic matrix with reproducibility demonstrated to be less than %RSD=7.0% for replicate samples measured over a 30-day period. In addition, repetitive samplings from one headspace aliquot are possible using one or more fibers and fiber types as well as quantitative options such as internal standard addition as demonstrated in a feasibility study using a benzene/toluene/xylene (BTX; 1 ppmv) certified gas standard, in which the SPME measurement precision (%RSD) was improved by a factor of 1.5-1.9 compared to the use of an external standard.

Detecting radiation reaction at moderate laser intensities.

We propose a new method of detecting radiation reaction effects in the motion of particles subjected to laser pulses of moderate intensity and long duration. The effect becomes sizable for particles that gain almost no energy through the interaction with the laser pulse. Hence, there are regions of parameter space in which radiation reaction is actually the dominant influence on charged particle motion.

Characterizing malignant liver lesions with contrast-enhanced ultrasound.

Microbubbles as an ultrasound contrast agent allow characterization of focal liver lesions. This article summarizes the ultrasound appearances and enhancement characteristics of malignant liver lesions, and also discusses its potential use for ultrasound-guided intervention and ablation of liver lesions.

Characterizing benign liver lesions and trauma with contrast-enhanced ultrasound.

Microbubbles as an ultrasound contrast agent allow characterization of focal liver lesions. This article summarizes the ultrasound appearances and enhancement characteristics of benign liver lesions, focal fatty sparing and focal fatty change, and blunt liver trauma.

Malate dehydrogenase 2 confers docetaxel resistance via regulations of JNK signaling and oxidative metabolism.

BACKGROUND: Resistance to chemotherapy represents a significant obstacle in prostate cancer therapeutics. Novel mechanistic understandings in cancer cell chemotherapeutic sensitivity and resistance can optimize treatment and improve patient outcome. Molecular alterations in the metabolic pathways are associated with cancer development; however, the role of these alterations in chemotherapy efficacy is largely unknown. METHODS: In a bed-side to bench-side reverse translational approach, we used cDNA microarray and qRT-PCR to identify genes that are associated with biochemical relapse after chemotherapy. Further, we tested the function of these genes in cell proliferation, metabolism, and chemosensitivity in prostate cancer cell lines. RESULTS: We report that the gene encoding mitochondrial malate dehydrogenase 2 (MDH2) is overexpressed in clinical prostate cancer specimens. Patients with MDH2 overexpression had a significantly shorter period of relapse-free survival (RFS) after undergoing neoadjuvant chemotherapy. To understand the molecular mechanism underlying this clinical observation, we observed that MDH2 expression was elevated in prostate cancer cell lines compared to benign prostate epithelial cells. Stable knockdown of MDH2 via shRNA in prostate cancer cell lines decreased cell proliferation and increased docetaxel sensitivity. Further, MDH2 shRNA enhanced docetaxel-induced activations of JNK signaling and induced metabolic inefficiency. CONCLUSION: Taken together, these data suggest a novel function for MDH2 in prostate cancer development and chemotherapy resistance, in which MDH2 regulates chemotherapy-induced signal transduction and oxidative metabolism.

Multiparametric ultrasonography of the testicles.

Ultrasonography is the standard modality to image the scrotum because it can provide information about volume, echo texture, tissue stiffness and functional information that includes macrovascularization and microvascularization. Indeed, ultrasound imaging is indicated in the presentation of acute scrotal pain and swelling to differentiate between testicular torsion, infarction and inflammation, as well as being the modality of choice when an intrascrotal mass is suspected. Advances in ultrasonography technology have produced new innovative techniques for imaging the scrotum, including grey-scale ultrasound, Doppler ultrasonography, contrast-enhanced ultrasonography and real-time sonoelastography. Each of these techniques provides information that can be useful when diagnosing diseases and disorders of the testicles. Consequently, the standard approach to accurate diagnosis should rely on multiparametric ultrasonography techniques, rather than just one or two techniques in isolation.

HDAC4 protein regulates HIF1α protein lysine acetylation and cancer cell response to hypoxia.

Hypoxia-inducible factor 1 α (HIF1α) is an essential part of the HIF-1 transcriptional complex that regulates angiogenesis, cellular metabolism, and cancer development. In von Hippel-Lindau (VHL)-null kidney cancer cell lines, we reported previously that HIF1α proteins can be acetylated and inhibited by histone deacetylase (HDAC) inhibitors or specific siRNA against HDAC4. To investigate the mechanism and biological consequence of the inhibition, we have generated stable HDAC4 knockdown via shRNA in VHL-positive normal and cancer cell lines. We report that HDAC4 regulates HIF1α protein acetylation and stability. Specifically, the HIF1α protein acetylation can be increased by HDAC4 shRNA and decreased by HDAC4 overexpression. HDAC4 shRNA inhibits HIF1α protein stability. In contrast, HDAC1 or HDAC3 shRNA has no such inhibitory effect. Mutations of the first five lysine residues (lysine 10, 11, 12, 19, and 21) to arginine within the HIF1α N terminus reduce protein acetylation but render the mutant HIF1α protein resistant to HDAC4 and HDACi-mediated inhibition. Functionally, in VHL-positive cancer cell lines, stable inhibition of HDAC4 decreases both the HIF-1 transcriptional activity and a subset of HIF-1 hypoxia target gene expression. On the cellular level, HDAC4 inhibition reduces the hypoxia-related increase of glycolysis and resistance to docetaxel chemotherapy. Taken together, the novel biological relationship between HDAC4 and HIF1α presented here suggests a potential role for the deacetylase enzyme in regulating HIF-1 cancer cell response to hypoxia and presents a more specific molecular target of inhibition.

Contrast enhanced ultrasound in the detection of liver metastases: a prospective multi-centre dose testing study using a perfluorobutane microbubble contrast agent (NC100100).

OBJECTIVE: To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy. METHODS: 157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 µL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the "Standard Of Reference" (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test. RESULTS: 165 metastases were present in 92 patients who each had 1-7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p = 0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p < 0.05). CONCLUSION: The diagnostic performance of CEUS is dose dependent with the 0.12 µL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases.

Contrast-enhanced ultrasound and prostate cancer; a multicentre European research coordination project.

CONTEXT: Contrast-enhanced ultrasound is a real-time imaging technique with the capability of visualizing perfusion patterns. Since tumour growth is associated with changes in vascularisation, this modality is under research for imaging of various tumour types. Studies have shown promising results for the diagnosis of prostate cancer for various imaging techniques; however, the exact value of each technique is still unclear. OBJECTIVE: To determine the value of contrast-enhanced ultrasound (CEUS) in the detection, localisation, and follow-up of treatment for prostate cancer. EVIDENCE ACQUISITION: In the period 2002-2006, research in four European centres regarding CEUS of the prostate was coordinated in a combined program. This paper describes and combines the results of these studies. EVIDENCE SYNTHESIS: Various techniques were developed and researched during the period of this program. Studies showed that prostate cancer could be visualized and localized in up to 78%. Visualization of the tumour enabled better detection; targeted biopsies lead to fewer biopsies per session without loss of detection rate. A combined approach offered the highest detection rate. CEUS could be used to visualize the effects of high-intensity focussed ultrasound and hormonal therapy for prostate cancer with success, and identified patients with an early relapse. Unfortunately, pretreatment evaluation could not identify the nonresponders beforehand. CONCLUSIONS: This research project was a first step towards routine use of CEUS in the clinical detection and follow-up of prostate cancer; and new combined studies are initiated.