Patterns of Circulating Cytokines and Vascular Markers' Response in the Presence of COVID-19 in Kidney Transplant Recipients Compared with Non-Transplanted Patients.

COVID-19's severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients' differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects.

OBJECTIVE: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. METHOD: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. RESULTS: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007.  Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. CONCLUSIONS: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic.

OBJECTIVE: The proportion of children with complex chronic conditions is increasing in PICUs around the world. We determined the prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic. METHODS: The authors conducted a point prevalence cross-sectional study among fifteen Brazilian PICUs during the COVID-19 pandemic. The authors enrolled all children admitted to the participating PICUs with complex chronic conditions on three different days, four weeks apart, starting on April 4th, 2020. The authors recorded the patient's characteristics and functional status at admission and discharge days. RESULTS: During the 3 study days from March to June 2020, the authors enrolled 248 patients admitted to the 15 PICUs; 148 had CCC (prevalence of 59.7%). Patients had a median of 1 acute diagnosis and 2 chronic diagnoses. The use of resources/devices was extensive. The main mode of respiratory support was conventional mechanical ventilation. Most patients had a peripherally inserted central catheter (63.1%), followed by a central venous line (52.5%), and 33.3% had gastrostomy or/and tracheostomy. The functional status score was significantly better at discharge compared to admission day due to the respiratory status improvement. CONCLUSIONS: The prevalence of children with CCC admitted to the Brazilian PICUs represented 59.7% of patients during the COVID-19 pandemic. The functional status of these children improved during hospitalization, mainly due to the respiratory component.

Tracheostomy practices in children on mechanical ventilation: a systematic review and meta-analysis.

OBJECTIVE: To evaluate current practices of tracheostomy in children regarding the ideal timing of tracheostomy placement, complications, indications, mortality, and success in decannulation. SOURCE OF DATA: The authors searched PubMed, Embase, Cochrane Library, Google Scholar, and complemented by manual search. The guidelines of PRISMA and MOOSE were applied. The quality of the included studies was evaluated with the Newcastle-Ottawa Scale. Information extracted included patients' characteristics, outcomes, time to tracheostomy, and associated complications. Odds ratios (ORs) with 95% CIs were computed using the Mantel-Haenszel method. SYNTHESIS OF DATA: Sixty-six articles were included in the qualitative analysis, and 8 were included in the meta-analysis about timing for tracheostomy placement. The risk ratio for "death in hospital outcome" did not show any benefit from performing a tracheostomy before or after 14 days of mechanical ventilation (p = 0.49). The early tracheostomy before 14 days had a great impact on the days of mechanical ventilation (-26 days in mean difference, p < 0.00001). The authors also found a great reduction in hospital length of stay (-31.4 days, p < 0.008). For the days in PICU, the mean reduction was of 14.7 days (p < 0.007). CONCLUSIONS: The meta-analysis suggests that tracheostomy performed in the first 14 days of ventilation can reduce the time spent on the ventilator, and the length of stay in the hospital, with no effect on mortality. The decision to perform a tracheostomy early or late may be more dependent on the baseline disease than on the time spent on ventilation .

Prolonged Mechanical Ventilation in Children: Review of the Definition.

OBJECTIVES: To review existing definitions of prolonged mechanical ventilation in children. DESIGN: Review of the literature. SETTING: Not applicable. PATIENTS: Pediatric patients under mechanical ventilation. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We searched the literature for original research on prolonged mechanical ventilation in children using the PubMed, Embase, and Cochrane Library databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and we extracted patient characteristics, duration of mechanical ventilation, outcomes, and associated complications. We identified 30 articles for qualitative analysis and found a wide variety of definitions, varying from 48 hours to 6 months. The most frequently used definitions of prolonged mechanical ventilation were greater than 7 days, greater than 14 days, and greater than 21 days. There was no high-quality evidence of a definition for prolonged mechanical ventilation in children. CONCLUSIONS: There is limited evidence to determine the definition of prolonged mechanical ventilation in children. The variety of definitions is a sign of the need for a consensus definition of pediatric prolonged mechanical ventilation.

A pharmacokinetic model for voriconazole in a highly diversified population of children and adolescents with cancer.

BACKGROUND: The wide pharmacokinetic variability of voriconazole leads to uncertainty regarding adequate exposure. OBJECTIVES: To create a pharmacokinetic model that could help to explain the variability. METHODS: Retrospective review of paediatric patients with cancer. Models were built using Pmetrics. RESULTS: We analysed 158 trough measurements in 55 patients; in 41.8%, the serum levels were between 1 and 6 mg/L on initial measurement. After the measurements, dosage adjustments were made in 42 (76.3%) patients, and the percentage of adequate levels rose to 54.5%. Fourteen deaths (25.4%) were attributed to invasive fungal diseases. The mean serum levels were higher in deceased patients (mean ± SD: 3.1 ± 3.2 mg/L vs 2.5 ± 3.6 mg/L in survivors; P = 0.018), but the median doses per kg were higher in survivors. Drug exposure was also higher in deceased patients (mean ± SD of AUC: 19.2 ± 8.1 vs 9.5 ± 19.1 in survivors; P = 0.005). No correlation was found between serum concentrations <1 mg/L and death attributable to fungal disease. Bioavailability was estimated in 50%. The maximum velocity of clearance was reduced in deceased patients. CONCLUSIONS: Extremely ill patients can be poor metabolizers of voriconazole. Therapeutic monitoring promotes only a limited improvement in drug management.

Cytokine Kinetics in Febrile Neutropenic Children: Insights on the Usefulness as Sepsis Biomarkers, Influence of Filgrastim, and Behavior of the IL-23/IL-17 Pathway.

BACKGROUND: The study aimed to describe the kinetics of various cytokines from day 1 to day 14 of the onset of fever in neutropenic children and to evaluate their performances as discriminators of sepsis in the first 24 hours of fever, the possible influence of filgrastim, and the functioning of the IL-23/IL-17 axis. METHODS: IL-1ß, TNF-α, IL-10, IL-12/23p40, IL-21, IL-6, IL-8, IL-17, G-CSF, and GM-CSF were measured in plasma on days 1, 2, 3, 5, and 14 from the onset of fever in 35 patients. RESULTS: Thirteen patients (37.1%) developed sepsis. In mixed models, IL-6, IL-8, IL-10, and G-CSF showed higher estimated means in septic patients (P < 0.005), and IL-12/23p40 and IL-17 in nonseptic patients (P < 0.05). On day 1, IL-6, IL-8, and IL-10 appeared upregulated in patients who received filgrastim. Only IL-6, IL-8, IL-10, and procalcitonin were useful as discriminators of sepsis. Associating the markers with each other or to a risk assessment model improved performance. CONCLUSIONS: Cytokines kinetics showed proinflammatory and anti-inflammatory responses similar to what is described in nonneutropenic patients. IL-8, IL-6, IL-10, and procalcitonin are useful as early biomarkers of sepsis. Filgrastim upregulates expression of these markers, and we observed deficiency in the IL-23-IL-17 axis accompanying sepsis.

Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit.

Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU), would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396) comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004) and in Group 3 (n=250) when cefepime was reintroduced (January to September 2005). Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017) and Group 3 (p=0.003). There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.