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Background/Objectives: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. Methods: Fifty-two patients with COVID-19 admitted to two tertiary care centers were included. They were divided into a severe group (intubated + mechanical ventilation) (n = 10) and a moderate group (non-intubated + oxygen administration) (n = 42), and changes over time in plasma NP, plasma BPs, IFN-γ, lymphocyte count, CRP, and IL-6 were investigated. Four of the patients in the severe group (n = 10) developed secondary bacterial infections during treatment. Plasma NP and plasma BPs of patients with bacterial sepsis (no viral infection) (n = 25) were also examined. Results: The plasma NP, IL-6, CRP, and SOFA levels were significantly higher in the severe group, while the IFN-γ level and lymphocyte count were significantly lower. The higher plasma NP in the severe group persisted only up to 1 week after symptom onset. The plasma BPs were higher in complications of bacterial infection. Conclusions: The timing of sample collection is important for assessing severity through plasma NP, while plasma BPs may be a useful diagnostic tool for identifying the development of secondary bacterial infection in patients with COVID-19. Further investigation is needed to clarify the mechanism by which NP and BPs, which are involved in the same biosynthetic pathway, are differentially activated depending on the type of pathogen. [ABSTRACT FROM AUTHOR]

Background Congenital heart disease (CHD) is a structural deformity of the heart present at birth. Pulmonary hypertension (PH) may arise from increased blood flow to the lungs, persistent pulmonary arterial pressure elevation, or the use of cardiopulmonary bypass (CPB) during surgical repair. Inhaled nitric oxide (iNO) selectively reduces high blood pressure in the pulmonary vessels without lowering systemic blood pressure, making it useful for treating children with postoperative PH due to heart disease. However, reducing or stopping iNO can exacerbate postoperative PH and hypoxemia, necessitating long-term administration and careful tapering. This study aimed to evaluate, using machine learning (ML), factors that predict the need for long-term iNO administration after open heart surgery in CHD patients in the postoperative ICU, primarily for PH management. Methods We used an ML approach to establish an algorithm to predict 'patients with long-term use of iNO' and validate its accuracy in 34 pediatric postoperative open heart surgery patients who survived and were discharged from the ICU at Kagoshima University Hospital between April 2016 and March 2019. All patients were started on iNO therapy upon ICU admission. Overall, 16 features reflecting patient and surgical characteristics were utilized to predict the patients who needed iNO for over 168 hours using ML analysis with AutoGluon. The dataset was randomly classified into training and test cohorts, comprising 80% and 20% of the data, respectively. In the training cohort, the ML model was constructed using the important features selected by the decrease in Gini impurity and a synthetic oversampling technique. In the testing cohort, the prediction performance of the ML model was evaluated by calculating the area under the receiver operating characteristics curve (AUC) and accuracy. Results Among 28 patients in the training cohort, five needed iNO for over 168 hours; among six patients in the testing cohort, one needed iNO for over 168 hours. CPB, aortic clamp time, in-out balance, and lactate were the four most important features for predicting the need for iNO for over 168 hours. In the training cohorts, the ML model achieved perfect classification with an AUC of 1.00. In the testing cohort, the ML model also achieved perfect classification with an AUC of 1.00 and an accuracy of 1.00. Conclusion The ML approach identified that four factors (CPB, in-out balance, aortic cross-clamp time, and lactate) are strongly associated with the need for long-term iNO administration after open heart surgery in CHD patients. By understanding the outcomes of this study, we can more effectively manage iNO administration in postoperative open heart surgery in CHD patients with PH, potentially preventing the recurrence of postoperative PH and hypoxemia, thereby contributing to safer patient management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Kagoshima University's Ethics Committee for Epidemiological Research issued approval 190250epi. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Niiyama et al.)

A 25-years-old man experienced fever and diarrhea. Ten days later he noticed difficulty walking (day 1). On admission neurological examination revealed lethargy, dysarthria and weakness of limbs. Oculocephalic response was not be elicited and extensor toe signs were positive. In spite of treatment with aciclovir and methylprednisolone, he continued to show progressive deterioration developing to coma with decorticate posture. Autonomic symptoms (hyperhidrosis, hypersalivation and fever) and groaning were observed. Brain magnetic resonance image and brainstem evoked potential presented no abnormality, but electroencephalographic study showed a spindle pattern indicating spindle coma. Laboratory tests including cerebrospinal fluids showed no specific results. High-dose immunoglobulin was administered from day 6, and his consciousness level improved. External ophthalomoplegia and ataxic gait were observed after he became more alert. Because he had IgG type anti-GQ1b antibodies in the serum, a diagnosis was made of Bickerstaff's brainstem encephalitis (BBE). Six months after discharge he had complete resolution of his symptoms. This is the first report of spindle coma observed in a case of serologically confirmed BBE.