Objective
To describe and analyze the characteristics and the early risk factors for mortality of noninvasive ventilation (NIV) in critically ill children.
Study design
A multicenter, prospective, ...observational 2‐year study carried out with critically ill patients (1 month – 18 years of age) who needed NIV. Clinical data and NIV parameters during the first 12 h of admission were collected. A multilevel mixed‐effects logistic regression was performed to identify mortality risk factors.
Results
A total of 781 patients (44.2 ± 57.7 months) were studied (57.8% male). Of them, 53.7% had an underlying condition, and 47.1% needed NIV for lower airway respiratory pathologies. Bi‐level NIV was the initial support in 78.2% of the patients. Continuous positive airway pressure (CPAP) was used more in younger patients (33.7%) than in older ones (9.7%; p < .001). About 16.7% had to be intubated and 6.2% died. The risk factors for mortality were immunodeficiency (odds ratio OR = 11.79; 95% confidence interval CI = 2.95–47.13); cerebral palsy (OR = 5.86; 95% CI = 1.94–17.65); presence of apneas on admission (OR = 5.57; 95% CI = 2.13–14.58); tachypnea 6 h after NIV onset (OR = 2.59; 95% CI = 1.30–6.94); and NIV failure (OR = 6.54; 95% CI = 2.79–15.34).
Conclusion
NIV is used with great variability in types of support. Younger children receive CPAP more frequently than older children. Immunodeficiency, cerebral palsy, apneas on admission, tachypnea 6 h after NIV onset, and NIV failure are the early factors associated with mortality.
Chemotherapy protocols for childhood cancers are still problematic due to the high toxicity associated with chemotherapeutic agents and incorrect dosing regimens extrapolated from adults. ...Nanotechnology has demonstrated significant ability to reduce toxicity of anticancer compounds. Improvement in the therapeutic index of cytostatic drugs makes this strategy an alternative to common chemotherapy in adults. However, the lack of nanomedicines specifically for pediatric cancer care raises a medical conundrum. This review highlights the current state and progress of nanomedicine in pediatric cancer and discusses the real clinical challenges and opportunities.
Transforming growth factor beta (TGF-β1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-β1 has been linked to cardiovascular disease in the general ...population. The immunosuppressive effect of TGF-β1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-β1 with subclinical carotid atherosclerosis in patients with SLE.
The study included 284 patients with SLE. Serum levels of TGF-β1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-β1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance.
Circulating TGF-β1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-β1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-β1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-β1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 95% confidence interval 1.003-1.30, p = 0.045).
TGF-β1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.
To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We ...aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.
New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.
Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.
Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects ...of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence.
What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?
We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators meeting in spring 2022 for open discussion. Feedback was incorporated, and final evaluation of research gaps are summarized herein. Although randomized controlled trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs also may be appropriate, given challenges with conducting large multicenter RCTs in children.
Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multicenter RCTs to provide definitive results, whereas other gaps can be addressed with multicenter observational studies or quality improvement initiatives. Furthermore, a need for some physiologic studies in several areas remains, particularly regarding newer diagnostic methods to improve identification of patients at high risk of extubation failure.
Although pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and multiple research gaps exist that should be filled through high-quality RCTs, multicenter observational studies, and quality improvement initiatives.
Transforming growth factor beta (TGF-β) is a highly pleiotropic cytokine that has broad anti-inflammatory and immunosuppressive effects. In patients with systemic lupus erythematosus (SLE), the ...immunosuppressive effect of TGF-β1 is thought to be dysfunctional. In the present work, we aimed to study the relationship between the serum levels of TGF-β1 with the characteristics of the disease as well as with the patterns of activity, damage, or severity of the disease. Two hundred and eighty-four patients with well-characterized SLE were recruited. The serum levels of TGF-β1 were assessed. A multivariable linear regression analysis was performed to analyze the relation of disease characteristics to TGF-β1. The Katz severity index (beta coefficient 179 95% confidence interval 7-350 pg/mL,
= 0.041) and SLEDAI activity index (beta coefficient 96 95% CI 20-171 pg/mL,
= 0.014) were associated with higher serum levels of TGF-β1 after the multivariable analysis. When the disease-specific features were studied, ocular and cardiovascular manifestations were positively associated with serum TGF-β1 levels. In contrast, gastrointestinal and musculoskeletal involvements were associated with lower levels of circulating TGF-β1. Among patients with SLE, the serum levels of TGF-β1 were highly associated with disease-related manifestations.
Abstract Despite the great advances that have been made in osteosarcoma therapy during recent decades, recurrence and metastases are still the most common outcome of the primary disease. Current ...treatments include drugs such as doxorubicin (DOX) that produce an effective response during the initial exposure of tumor cells but sometimes induce drug resistance within a few cycles of chemotherapy. New therapeutic strategies are therefore needed to overcome this resistance. To this end, DOX was loaded into lipid nanoparticles (LN) and its efficacy was evaluated in commercial and patient-derived metastatic osteosarcoma cell lines. DOX efficacy was heavily influenced by passage number in metastatic cells, in which an overexpression of P-gp was observed. Notably, DOX-LN overcame the resistance associated with cell passage and improved DOX efficacy fivefold. Moreover, when DOX was co-administered with either free or encapsulated edelfosine (ET), a synergistic effect was observed. This higher efficacy of the combined treatment was found to be at least partially due to an increase in caspase-dependent cell death. The combination of DOX and ET is thus likely to be effective against osteosarcoma.
Osteosarcoma (OS) is the most frequent paediatric bone cancer, responsible for 9% of all cancer-related deaths in children. In this paper, a new strategy based on delivering edelfosine (ET) in lipid ...nanoparticles (LN) was explored in order to target the primary tumour and eliminate metastases. The in vitro and in vivo efficacy of the free drug, drug loaded into lipid nanoparticles (ET-LN) and doxorubicin (DOX) against osteosarcoma (OS) cells was analysed. ET and ET-LN decreased the growth of OS cells in vitro in a time- and dose-dependent manner. Interestingly, the uptake of ET and ET-LN was lower when OS cells were pre-treated with DOX. In vivo studies revealed that ET and ET-LN slowed down the primary tumour growth in two OS models. However, the combination of both drugs showed no additional anti-tumour effect. Importantly, ET-LN successfully prevented the metastatic spread of OS cells from the primary tumour to the lungs. On the whole, ET-LN are a promising candidate for OS chemotherapy.
•Edelfosine and edelfosine loaded lipid nanoparticles inhibit osteosarcoma cell proliferation in vitro.•The uptake of ET and ET-LN is decreased when osteosarcoma cells are pre-treated with doxorubicin.•Orally administered ET-LN have an outstanding effect against primary OS tumours.•ET-LN successfully prevented the metastatic spread of OS cells from the primary tumour to the lungs.
Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus ...(SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.
Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with ...disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 95% confidence interval, -1.1 to -0.3) fL,
< 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.
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