Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular ...cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS.
This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS.
In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001).
COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19.
To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 ...patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile.
This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay.
Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference,
< 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels.
The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention.
ClinicalTrials.gov identifier NCT04343053.
The aim of this study (NCT04343053) is to investigate the relationship between platelet activation, myocardial injury, and mortality in patients affected by Coronavirus disease 2019 (COVID-19). ...Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion T1, after 7 ± 2 days T2 and 14 ± 2 days T3). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). In COVID-19 patients, P-selectin and sCD40L levels decreased from T1 to T3 and were higher in cases requiring admission to intensive care unit (p = .004 and p = .008, respectively). Patients with myocardial injury (37%), as well as those who died (30%), had higher values of all biomarkers of platelet activation (p < .05 for all). Myocardial injury was an independent predictor of mortality. In COVID-19 patients admitted to hospital for respiratory failure, heightened platelet activation is associated with severity of illness, myocardial injury, and mortality.
ClinicalTrials.gov number: NCT04343053.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and ...cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL.
Patients admitted to the intensive care unit (ICU) with an expected length of mechanical ventilation of 72 h were enrolled in this prospective, observational study. Patients were evaluated, within 24 h from ICU admission and for at least 72 h, in terms of respiratory mechanics, presence of EFL through the PEEP test, daily fluid balance and followed for outcome measurements.
Among the 121 patients enrolled, 37 (31%) exhibited EFL upon admission. Flow-limited patients had higher BMI, history of pulmonary or heart disease, worse respiratory dyspnoea score, higher intrinsic positive end-expiratory pressure, flow and additional resistance. Over the course of the initial 72 h of mechanical ventilation, additional 21 patients (17%) developed EFL. New onset EFL was associated with a more positive cumulative fluid balance at day 3 (103.3 ml/kg) compared to that of patients without EFL (65.8 ml/kg). Flow-limited patients had longer duration of mechanical ventilation, longer ICU length of stay and higher in-ICU mortality.
EFL is common among ICU patients and correlates with adverse outcomes. The major determinant for developing EFL in patients during the first 3 days of their ICU stay is a positive fluid balance. Further studies are needed to assess if a restrictive fluid therapy might be associated with a lower incidence of EFL.
Mechanically ventilated patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow ...could be more compromised in SARS-CoV-2 patients than in patients with “classical” ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Prospective, observational pilot study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Mechanical ventilation settings included constant-flow controlled ventilation, a tidal volume of 6 ml/kg of ideal body weight and the PEEP level titrated to the lowest driving pressure. Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.710.67–0.78 vs 0.640.60–0.74,
p
= 0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (
p
= 0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r
2
= 0.31;
p
= 0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (
p
= 0.46). We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with “classical” ARDS.
Guidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference ...(A-V O
), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion.
A prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0-10.0 g/dL within 72 h after ICU admission. The A-V O
, central venous oxygen saturation (ScvO
), and oxygen extraction ratio (O
ER) were noted when a patient's Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O
value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as "appropriate" (patient transfused when the A-V O
> 3.7 mL or not transfused when the A-V O
≤ 3.7 mL) or "inappropriate" (patient transfused when the A-V O
≤ 3.7 mL or not transfused when the A-V O
> 3.7 mL). The primary outcome was 90-day mortality.
Patients managed with an "appropriate" strategy had lower mortality rates (23/96 24% vs. 36/81 44%; p = 0.004), and an "appropriate" strategy was independently associated with reduced mortality (hazard ratio HR 0.51 95% CI 0.30-0.89, p = 0.01). There was a trend to less acute kidney injury with the "appropriate" than with the "inappropriate" strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O
, but not the ScvO
, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O
cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients.
In anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O
.
ClinicalTrials.gov, NCT03767127. Retrospectively registered on 6 December 2018.
During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is ...unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEP
INCREMENTAL
) or by stepwise decrease after a lung recruiting manoeuvre (PEEP
DECREMENTAL
). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEP
INCREMENTAL
or PEEP
DECREMENTAL
strategy to match the lowest ∆P. In the PEEP
INCREMENTAL
group, PEEP was stepwise titrated from ZEEP up to 16 cm H
2
O, whereas in the PEEP
DECREMENTAL
group PEEP was decrementally titrated, starting from 16 cm H
2
O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 39–55% to 35 28–42% in the PEEP
INCREMENTAL
and from 45 37–58% to 33 25–45% in the PEEP
DECREMENTAL
group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEP
DECREMENTAL
than in the PEEP
INCREMENTAL
group (8 7–11 vs 10 9–11 cm H
2
O; p = 0.03). In the PEEP
DECREMENTAL
group the PaO
2
/ FIO
2
ratio increased significantly after intervention (from 140 99–176 to 186 152–243, p < 0.001). Both the PEEP
INCREMENTAL
and the PEEP
DECREMENTAL
strategies were able to decrease intraoperative shunt, but only PEEP
DECREMENTAL
improved oxygenation and lowered intraoperative ΔP.
Clinical trial number
NCT03635281; August 2018; “retrospectively registered”
Electrical impedance tomography (EIT) is a non-invasive radiation-free monitoring technique that provides images based on tissue electrical conductivity of the chest. Several investigations applied ...EIT in the context of perioperative medicine, which is not confined to the intraoperative period but begins with the preoperative assessment and extends to postoperative follow-up.
EIT could provide careful respiratory monitoring in the preoperative assessment to improve preparation for surgery, during anaesthesia to guide optimal ventilation strategies and to monitor the hemodynamic status and in the postoperative period for early detection of respiratory complications. Moreover, EIT could further enhance care of patients undergoing perioperative diagnostic procedures. This narrative review summarizes the latest evidence on the application of this technique to the surgical patient, focusing also on possible future perspectives.
EIT is a promising technique for the perioperative assessment of surgical patients, providing tailored adaptive respiratory and haemodynamic monitoring. Further studies are needed to address the current technological limitations, confirm the findings and evaluate which patients can benefit more from this technology.
Beyond their role in hemostasis, platelets have emerged as key contributors in the immune response; accordingly, the occurrence of thrombocytopenia during sepsis/septic shock is a well-known risk ...factor of mortality and a marker of disease severity. Recently, some studies elucidated that the response of platelets to infections goes beyond a simple fall in platelets count; indeed, sepsis-induced thrombocytopenia can be associated with-or even anticipated by-several changes, including an altered morphological pattern, receptor expression and aggregation. Of note, alterations in platelet function and morphology can occur even with a normal platelet count and can modify, depending on the nature of the pathogen, the pattern of host response and the severity of the infection. The purpose of this review is to give an overview on the pathophysiological interaction between platelets and pathogens, as well as the clinical consequences of platelet dysregulation. Furthermore, we try to clarify how understanding the nature of platelet dysregulation may help to optimize the therapeutic approach.
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