Using machine learning to improve the diagnostic accuracy of the modified Duke/ESC 2015 criteria in patients with suspected prosthetic valve endocarditis - a proof of concept study.

INTRODUCTION: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [18F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms. METHODS: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard. RESULTS: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively. DISCUSSION: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [18F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE.

Increased volumes of mildly elevated capillary transit time heterogeneity positively predict favorable outcome and negatively predict intracranial hemorrhage in acute ischemic stroke with large vessel occlusion.

OBJECTIVES: In patients with acute ischemic stroke, we aimed to investigate whether microvascular changes, as indexed by capillary transit time heterogeneity (CTH), contribute to the decline of the chance for favorable outcome over time and whether they are a predictor of an intracranial hemorrhage (ICH). METHODS: We retrospectively calculated CTH maps for 131 consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation who had a relevant MRI PWI-DWI mismatch and were treated with endovascular thrombectomy (ET). Multivariable logistic regressions were conducted with favorable outcome (mRS ≤ 2 after 3 months) and occurrence of an ICH as dependent variables and the volume of mildly elevated CTH as independent variable adjusted for age, successful recanalization, hypertension, diabetes, atrial fibrillation, NIHSS score on admission, DWI lesion volume, and symptom-onset-to-treatment time (OTT). RESULTS: A larger volume of mildly elevated CTH was a positive predictor of favorable outcome (OR 1.17; 1.03-1.33; p = 0.019) and a negative predictor of ICH (OR 0.83; 0.73-0.96; p = 0.009). As expected, successful recanalization (OR 5.54; 1.8-17; p = 0.003), low NIHSS on admission (OR 0.9; 0.82-1.00; p = 0.045), short OTT (OR 0.96; 0.94-0.99; p = 0.006), and low DWI volume (OR 0.68; 0.49-0.94; p = 0.021) were also predictors of favorable outcome, whereas other negative predictors of ICH were atrial fibrillation (OR 2.69; 1.10-6.57; p = 0.030), high NIHSS score on admission (OR 1.10 (1.01-1.19); p = 0.030), and large DWI volume (OR 1.51; 1.17-1.19; p = 0.002). CONCLUSION: An increased volume of mildly elevated CTH is a positive predictor of favorable outcome and a negative predictor for ICH in patients with acute ischemic stroke and mismatch undergoing ET. KEY POINTS: • The classification of potentially salvageable tissue and infarct core based on traditional net perfusion parameters (as Tmax or CBF) does not account for the microvascular distribution of blood. • However, the microvascular distribution of blood, as indexed by the capillary transit time heterogeneity (CTH), directly affects the availability of oxygen within the hypoperfused tissue and should therefore be respected in acute ischemic stroke imaging. • In our study, mildly elevated CTH is found to be a positive predictor for a favorable clinical outcome and a negative predictor for the occurrence of an intracranial hemorrhage in patients with acute ischemic stroke and homogenous mismatch who underwent ET.

Olfactory function in Parkinson's Disease - effects of training.

BACKGROUND: Up to 90% of patients with Parkinson's disease (PD) exhibit olfactory dysfunction, but little is known about the effects of olfactory training. The study aim was to investigate whether the ability to identify olfactory stimuli can be improved by means of a brief training session. Furthermore, the impact of hyposmia on quality of life in PD was investigated by means of a questionnaire. METHODS: Olfactory function was rated in 34 patients with PD and in 26 controls before and after a training session. An additional 20 patients with PD served as a control group and were tested twice without an intervening training session. Long-term effects were evaluated in a small subset of patients. Cognitive tests and DaT SPECT scans were performed. RESULTS: We demonstrated significant same-day and long-term training effects in trained PD patients compared with non-trained PD patients. A slightly significant correlation was seen between the training effect and DaT putamen values, but not with cognitive test scores. Furthermore, patients with PD reported that hyposmia significantly decreased their quality of life. CONCLUSIONS: Patients with PD improved the number of correctly identified odors in an olfactory test through a brief training session. Olfactory training may have potential in rehabilitation of patients with PD.

Microcirculatory dysfunction and tissue oxygenation in critical illness.

Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high. The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen. We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

Remote ischemic perconditioning in thrombolysed stroke patients: randomized study of activating endogenous neuroprotection - design and MRI measurements.

BACKGROUND: Intravenous administration of alteplase is the only approved treatment for acute ischemic stroke. Despite the effectiveness of this treatment, 50% of patients suffer chronic neurological disability, which may in part be caused by ischemia-reperfusion injury. Remote ischemic perconditioning, performed as a transient ischemic stimulus by blood-pressure cuff inflation to an extremity, has proven effective in attenuating ischemia-reperfusion injury in animal models of stroke. Remote ischemic perconditioning increases myocardial salvage in patients undergoing acute revascularization for acute myocardial infarction. To clarify whether a similar benefit can be obtained in patients undergoing thrombolysis for acute stroke, we included patients from June 2009 to January 2011. AIM AND DESIGN: The aims of the study are: to estimate the effect of remote ischemic perconditioning as adjunctive therapy to intravenous alteplase of acute ischemic stroke within the 4-h time window and to investigate the feasibility of remote ischemic perconditioning performed during transport to hospital in patients displaying symptoms of acute stroke. Patients are randomized to remote ischemic perconditioning in a single-blinded fashion during transportation to hospital. Only patients with magnetic resonance imaging-proven ischemic stroke, who subsequently are treated with intravenous alteplase, and in selected cases additional endovascular treatment, are finally included in the study. STUDY OUTCOMES: Primary end-point is penumbral salvage. Penumbra is defined as hypoperfused yet viable tissue identified as the mismatch between perfusion-weighted imaging and diffusion-weighted imaging lesion on magnetic resonance imaging scans. Primary outcome is a mismatch volume not progressing to infarction on one-month follow-up T2 fluid attenuated inversion recovery. Secondary end-points include: infarct growth (expansion of the diffusion-weighted imaging lesion) from baseline to the 24-h and one-month follow-up examination. Infarct growth inside and outside the acute perfusion-weighted imaging-diffusion-weighted imaging mismatch zone is quantified by use of coregistration. Clinical outcome after three-months. The influence of physical activity (Physical Activity Scale for the Elderly score) on effect of remote ischemic perconditioning. Feasibility of remote ischemic perconditioning in acute stroke patients. SUMMARY: This phase 3 trial is the first study in patients with acute ischemic stroke to evaluate the effect size of remote ischemic perconditioning as a pretreatment to intravenous alteplase, measured as penumbral salvage on multimodal magnetic resonance imaging and clinical outcome after three-months follow-up.

It don't mean a thing... Keeping the rhythm during polyrhythmic tension, activates language areas (BA47).

Music is experienced and understood on the basis of foreground/background relationships created between actual music and the underlying meter. In contemporary styles of music so-called polyrhythmic, structures hence create tension between a counter pulse and the main pulse. This exerts a marked influence on the listener, particularly when the experience of the original meter is maintained during the counter pulse. We here demonstrate that Brodmann area 47, an area associated with higher processing of language, is activated bilaterally when musicians tap the main pulse in a polymetric context where the music emphasizes a counter meter. This suggests that the processing of metric elements of music relies on brain areas also involved in language comprehension. We propose that BA47 is involved in general neuronal processing of temporal coherence subserving both language and music.