Objectives: To propose the optimal timing to consider tracheostomy insertion for weaning of mechanically ventilated patients recovering from coronavirus disease 2019 pneumonia. We investigated the relationship between duration of mechanical ventilation prior to tracheostomy insertion and in-hospital mortality. In addition, we present a machine learning approach to facilitate decision-making. Design: Prospective cohort study. Setting: Guy’s & St Thomas’ Hospital, London, United Kingdom. Patients: Consecutive patients admitted with acute respiratory failure secondary to coronavirus disease 2019 requiring mechanical ventilation between March 3, 2020, and May 5, 2020. Interventions: Baseline characteristics and temporal trends in markers of disease severity were prospectively recorded. Tracheostomy was performed for anticipated prolonged ventilatory wean when levels of respiratory support were favorable. Decision tree was constructed using C4.5 algorithm, and its classification performance has been evaluated by a leave-one-out cross-validation technique. Measurements and Main Results: One-hundred seventy-six patients required mechanical ventilation for acute respiratory failure, of which 87 patients (49.4%) underwent tracheostomy. We identified that optimal timing for tracheostomy insertion is between day 13 and day 17. Presence of fibrosis on CT scan (odds ratio, 13.26; 95% CI [3.61–48.91]; p ≤ 0.0001) and Pao 2:Fio 2 ratio (odds ratio, 0.98; 95% CI [0.95–0.99]; p = 0.008) were independently associated with tracheostomy insertion. Cox multiple regression analysis showed that chronic obstructive pulmonary disease (hazard ratio, 6.56; 95% CI [1.04–41.59]; p = 0.046), ischemic heart disease (hazard ratio, 4.62; 95% CI [1.19–17.87]; p = 0.027), positive end-expiratory pressure (hazard ratio, 1.26; 95% CI [1.02–1.57]; p = 0.034), Pao 2:Fio 2 ratio (hazard ratio, 0.98; 95% CI [0.97–0.99]; p = 0.003), and C-reactive protein (hazard ratio, 1.01; 95% CI [1–1.01]; p = 0.005) were independent late predictors of in-hospital mortality. Conclusions: We propose that the optimal window for consideration of tracheostomy for ventilatory weaning is between day 13 and 17. Late predictors of mortality may serve as adverse factors when considering tracheostomy, and our decision tree provides a degree of decision support for clinicians.

The prevalence of some chronic diseases, such as cancer or neurodegenerative disorders, differs between sexes. Animal models provide an important tool to adopt potential therapies from preclinical studies to humans. Laboratory rats are the most popular animals in toxicology, neurobehavioral, or cancer research. Our study aimed to reveal the basic differences in blood metabolome (amino acids, biogenic amines, and acylcarnitines) of the adult male (n = 10) and female (n = 10) Wistar rats. Partial least square-discrimination analysis (PLS-DA) and a variance im portance in projection (VIP) score was used to identify the key sex-specific metabolites. All groups of metabolites, as the main markers of energy metabolism, showed a significant sex-dependent pattern. The most important features calculated in PLS-DA according to VIP score were free carnitine (C0), tyrosine (Tyr), and acylcarnitine C5-OH. While aromatic amino acids, such as Tyr and phenylalanine (Phe), were significantly elevated in the blood plasma of males, tryptophan (Trp) was found in higher levels in the blood plasma of females. Besides, significant sex-related changes in urea cycle were found. Our study provides an important insight into sex-specific differences in energy metabolism in rats and indicates that further studies should consider sex as the main aspect in design and data interpretation.

Lipid peroxidation (LPX) can play an important role in the development of pathological changes of foetal and neonatal tissues. We investigated LPX and biochemical parameters in plasma from mixed umbilical cord (m.u.c.) blood and acid-base balance (ABB) parameters in m.u.c. blood of well-adapted full-term newborns. LPX products were estimated as thiobarbituric acid reacting substances (TBARS) and were expressed by using of malondialdehyde (MDA) as a standard solution. Intensity of LPX was estimated in vitro in m.u.c. blood plasma without and with added LPX activator (125 µM L-ascorbate plus 5 µM FeSO4) and in the incubated plasma (30 min, 37• C) under both conditions. Actual TBARS (3.51 ± 0.49 nmol/mL) were determined in the non-incubated plasma without the added LPX activator. Approximately twice higher TBARS were found in the incubated plasma without the LPX activator (7.29 ± 2.17 nmol/mL) or with it (8.57 ± 2.20 nmol/mL), as well as in the non-incubated plasma after its addition (7.38 ± 1.98 nmol/mL). All analysed biochemical parameters (Fe, total iron-binding capacity, uric acid, proteins, Mg, Ca, phosphate, glucose, K, Na, Cl, ALT, AST, GMT, CK, LD, HBD, AMS, ALP, ACP) and ABB parameters were within their reference ranges. The actual TBARS levels were found being positively correlated with α-hydroxybutyrate dehydrogenase (HBD) activity and negatively with pO2. These results suggest that LPX in m.u.c. blood plasma might be activated. This activation could probably depend on extent of hypoxia. TBARS and their formation in vitro could be suitable parameters of LPX in m.u.c. blood.

Lipid peroxidation (LPX) can play an important role in development of functional and pathological changes of maternal tissues in the course of pregnancy and delivery. LPX products were measured as thiobarbituric acid reacting substances (TBARS), using malondialdehyde as the standard solution. Actual TBARS determined in maternal post-delivery plasma (2.71 ± 0.602 nmol/mL) were not statistically different from those determined in pre-delivery plasma (3.45 ± 0.530 nmol/mL). TBARS production was measured in vitro in the both incubated plasma (30 min, 37• C) with and without the added LPX activator (125 µM L-ascorbate plus 5 µM FeSO4). A difference in the TBARS formation was found only in the post-delivery plasma, as a result of approximately twice higher (marginally significant) TBARS formation in the incubated plasma without the added LPX activator comparing with the actual TBARS levels in this plasma. These results suggest that changes in maternal tissues in the process of labour could create suitable conditions for activation of LPX in maternal plasma. On the other hand, all other analysed biochemical parameters (iron, total iron-binding capacity, uric acid, proteins, magnesium, calcium, phosphate, glucose, potassium, sodium, chlorides, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, creatine kinase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, α-amylase, alkaline phosphatase, acid phosphatase in the post-delivery plasma were not different from those analysed in the pre-delivery plasma.

A new method in decision-making of timing of tracheostomy in COVID-19 patients is developed and discussed in this paper. Tracheostomy is performed in critically ill coronavirus disease (COVID-19) patients. The timing of tracheostomy is important for anticipated prolonged ventilatory wean when levels of respiratory support were favorable. The analysis of this timing has been implemented based on classification method. One of principal conditions for the developed classifiers in decision-making of timing of tracheostomy in COVID-19 patients was a good interpretation of result. Therefore, the proposed classifiers have been developed as decision tree based because these classifiers have very good interpretability of result. The possible uncertainty of initial data has been considered by the application of fuzzy classifiers. Two fuzzy classifiers as Fuzzy Decision Tree (FDT) and Fuzzy Random Forest (FRF) have been developed for the decision-making in tracheostomy timing. The evaluation of proposed classifiers and their comparison with other show the efficiency of the proposed classifiers. FDT has best characteristics in comparison with other classifiers.

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