Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often ...deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.
7,8 In addition, machine learning has been applied to the ever so challenging (1) heart failure patients with preserved ejection fraction and helped to set up a new phenotypic risk assessment system ...for heart failure9 and also (2) patients with either hypertrophic cardiomyopathy or athletes LV hypertrophy based on expert-annotated, speckle-tracking of echocardiograms. 15 A machine learning in the form of support vector machine devised an effective risk calculator that was shown to be superior (less-recommended drug therapy with less adverse events) to the existing accepted American College of Cardiology (ACC)/ American Heart Association (AHA) cardiovascular disease risk calculator. 20 In addition, four AI-based algorithms were employed to facilitate a clinical decision support system for estimating risk in congenital heart surgery. 21 One innovative report described using machine learning and system modeling to facilitate a multicentric collaborative learning project for rapid structured fact-finding and dissemination of expertise; this forward-thinking approach can provide a complement (and perhaps render less necessary to) the traditional multi-center, randomized clinical trials that are sometimes challenging to execute.
The COVID-19 pandemic has lead to catastrophic number of deaths and revealed that much work still remains with data and artificial intelligence. To fully comprehend the dynamics of a pandemic with ...relevance to artificial intelligence, a primer on global health concepts is first presented. Following this, various aspects of diagnosis and therapy and the relationship to artificial intelligence are presented along with a future projection of an ideal deployment of artificial intelligence in a pandemic. Final thoughts are made about lessons learned and what lies ahead.
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•The COVID-1 pandemic has reminded us the dire need for public health interventions as well as data and artificial intelligence.•Artificial intelligence has many potential applications in pandemic situations, from diagnosis to therapy.•Advances in artificial intelligence can lead to better disease modeling as well as protein structure prediction, drug repurposing, and vaccine designs.•The pandemic is a clarion call for clinicians and policymakers to accelerate the adoption of artificial intelligence.
Persistently elevated posttreatment plasma EBV DNA is a robust predictor of relapse in nasopharyngeal carcinoma (NPC). However, assay standardization is necessary for use in biomarker-driven trials. ...We conducted a study to harmonize the method between four centers with expertise in EBV DNA quantitation.
Plasma samples of 40 patients with NPC were distributed to four centers. DNA was extracted and EBV DNA copy number was determined by real-time quantitative PCR (BamHI-W primer/probe). Centers used the same protocol but generated their own calibrators. A harmonization study was then conducted using the same calibrators and PCR master mix and validated with ten pooled samples.
The initial intraclass correlations (ICC) for the first 40 samples between each center and the index center were 0.62 95% confidence interval (CI): 0.39-0.78, 0.70 (0.50-0.83), and 0.59 (0.35-0.76). The largest variability was the use of different PCR master mixes and calibrators. Standardization improved ICC to 0.83 (0.5-0.95), 0.95 (0.83-0.99) and 0.96 (0.86-0.99), respectively, for ten archival frozen samples. For fresh plasma with spiked-in EBV DNA, correlations were more than 0.99 between the centers. At 5 EBV DNA copies per reaction or above, the coefficient of variance (CV) was less than 10% for the cycle threshold (Ct) among all centers, suggesting this concentration can be reliably used as a cutoff for defining the presence of detectable EBV DNA.
Quantitative PCR assays, even when conducted in experienced clinical labs, can yield large variability in plasma EBV DNA copy numbers without harmonization. The use of common calibrators and PCR master mix can help to reduce variability.
Personality traits and affective states are associated with biases in facial emotion perception. However, the precise personality impairments and affective states that underlie these biases remain ...largely unknown. To investigate how relevant factors influence facial emotion perception and recollection, Experiment 1 employed an image reconstruction approach in which community-dwelling adults (N = 89) rated the similarity of pairs of facial expressions, including those recalled from memory. Subsequently, perception- and memory-based expression representations derived from such ratings were assessed across participants and related to measures of personality impairment, state affect, and visual recognition abilities. Impairment in self-direction and level of positive affect accounted for the largest components of individual variability in perception and memory representations, respectively. Additionally, individual differences in these representations were impacted by face recognition ability. In Experiment 2, adult participants (N = 81) rated facial image reconstructions derived in Experiment 1, revealing that individual variability was associated with specific visual face properties, such as expressiveness, representation accuracy, and positivity/negativity. These findings highlight and clarify the influence of personality, affective state, and recognition abilities on individual differences in the perception and recollection of facial expressions.
•Multiple factors systematically impact perception and memory for facial expressions.•Personality functioning and affective states modulate expression representations.•General face recognition abilities also impact representations.•These factors introduce considerable pictorial changes in face representations.
To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE).
Prospective observational study.
Nineteen children between the ...ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included.
All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality.
Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE.
Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%-100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%-70%) of misinterpretation of PE as PPE.
The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.
Migraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence ...tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).
We recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.
On macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.
Migraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.
Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy ...and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS.
The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25- microg/kg bolus over 60 minutes followed by a 0.25- microg/kg per min infusion for 35 hours; high dose, 75- microg/kg bolus followed by a 0.75- microg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P=0.023) in 238 treated patients and 64% (P=0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049).
The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.
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