Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone.

This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.

Predictors of outcomes of patients ≥ 80 years old admitted to intensive care units in Poland - a post-hoc analysis of the VIP2 prospective observational study.

INTRODUCTION: Elderly patients pose a significant challenge to intensive care unit (ICU) clinicians. In this study we attempted to characterise the population of patients over 80 years old admitted to ICUs in Poland and identify associations between clinical features and short-term outcomes. MATERIAL AND METHODS: The study is a post-hoc analysis of the Polish cohort of the VIP2 European prospective observational study enrolling patients > 80 years old admitted to ICUs over a 6-month period. Data including clinical features, clinical frailty scale (CFS), geriatric scales, interventions within the ICU, and outcomes (30-day and ICU mortality and length of stay) were gathered. Univariate analyses comparing frail (CFS > 4) to non-frail patients and survivors to non-survivors were performed. Multivariable models with CFS, activities of daily living score (ADL), and the cognitive decline questionnaire IQCODE as predictors and ICU or 30-day mortality as outcomes were formed. RESULTS: A total of 371 patients from 27 ICUs were enrolled. Frail patients had significantly higher ICU (58% vs. 44.45%, P = 0.03) and 30-day (65.61% vs. 54.14%, P = 0.01) mortality compared to non-frail counterparts. The survivors had significantly lower SOFA score, CFS, ADL, and IQCODE than non-survivors. In multivariable analysis CFS (OR 1.15, 95% CI: 1.00-1.34) and SOFA score (OR 1.29, 95% CI: 1.19-1.41) were identified as significant predictors for ICU mortality; however, CFS was not a predictor for 30-day mortality ( P = 0.07). No statistical significance was found for ADL, IQCODE, polypharmacy, or comorbidities. CONCLUSIONS: We found a positive correlation between CFS and ICU mortality, which might point to the value of assessing the score for every patient admitted to the ICU. The older Polish ICU patients were characterised by higher mortality compared to the other European countries.

Prevalence of life-sustaining treatment limitations in Polish very old intensive care patients (VIPs). A post-hoc analysis of two prospective observational studies.

PURPOSE: Several initiatives have recently focused on raising awareness about limitations of treatment in Poland. We aimed to assess if the propensity to limit LST among elderly patients in 2018-2019 increased compared to 2016-2017. METHODS: We analysed Polish cohorts from studies VIP1 (October 2016 - May 2017) and VIP2 (May 2018 - May 2019) that enrolled critical patients aged >80. We collected data on demographics, clinical features limitations of LST. Primary analysis assessed factors associated with prevalence of limitations of LST, A secondary analysis explored differences between patients with and without limitations of LST. RESULTS: 601 patients were enrolled. Prevalence of LST limitations was 16.1% in 2016-2017 and 20.5% in 2018-2019. No difference was found in univariate analysis (p = 0.22), multivariable model showed higher propensity towards limiting LST in the 2018-2019 cohort compared to 2016-2017 cohort (OR 1.07;95%CI, 1.01-1.14). There was higher mortality and a longer length of stay of patients with limitations of LST compared to the patients without limitations of LST. (11 vs. 6 days, p = 0.001). CONCLUSIONS: The clinicians in Poland have become more proactive in limiting LST in critically ill patients ≥80 years old over the studied period, however the prevalence of limitations of LST in Poland remains low.

Changes in plasma endocan level are related to circulatory but not respiratory failure in critically ill patients with COVID-19.

The aim of this prospective, observational study was to assess whether changes in the level of endocan, a marker of endothelial damage, may be an indicator of clinical deterioration and mortality in critically ill COVID-19 patients. Endocan and clinical parameters were evaluated in 40 patients with acute respiratory failure on days 1-5 after admission to the intensive care unit. Endocan levels were not related to the degree of respiratory failure, but to the presence of cardiovascular failure. In patients with cardiovascular failure, the level of endocan increased over the first 5 days (1.63, 2.50, 2.68, 2.77, 3.31 ng/mL, p = 0.016), while in patients without failure it decreased (1.51, 1.50, 1.56, 1.42, 1.13 ng/mL, p = 0.046). In addition, mortality was more than twice as high in patients with acute cardiovascular failure compared to those without failure (68% vs. 32%, p = 0.035). Baseline endocan levels were lower in viral than in bacterial infections (1.57 ng/mL vs. 5.25 ng/mL, p < 0.001), with a good discrimination between infections of different etiologies (AUC of 0.914, p < 0.001). In conclusion, endocan levels are associated with the occurrence of cardiovascular failure in COVID-19 and depend on the etiology of the infection, with higher values for bacterial than for viral sepsis.

Intraoperative intravenous infusion of lidocaine increases total and small vessel densities of sublingual microcirculation: a randomized prospective pilot study.

OBJECTIVE: Multiple organ failure can occur as a result of postoperative complications. Research has indicated that the underlying mechanism of organ dysfunction is a microcirculation disorder. Because of its antioxidant and anti-inflammatory properties, lidocaine has the potential to improve microvascular blood flow. This study was performed to assess the effect of intraoperative intravenous lidocaine infusion on the microcirculation and determine the incidence of postoperative complications. METHODS: In this prospective randomized double-blind pilot study, 12 patients scheduled for abdominal surgery were randomly allocated to receive an intraoperative infusion of either 1% lidocaine or the same volume of 0.9% sodium chloride solution. The microcirculation was monitored using sidestream dark-field imaging and the vascular occlusion test combined with near-infrared spectroscopy. RESULTS: Lidocaine significantly increased the total vascular density and small vessel density after 2 hours of infusion, with preservation of 99% to 100% of the capillary perfusion in both groups. No patients developed organ failure. CONCLUSIONS: An increase in vessel density may be beneficial in major abdominal surgeries because it is associated with better tissue perfusion and oxygen delivery. However, this finding requires further investigation in patients with increased surgical risk. Overall, this study indicates that lidocaine has potential to improve microvascular perfusion.Research Registry number: 9549 (https://www.researchregistry.com/browse-the-registry#home/registrationdetails/650ffd27b3f547002bd7635f/).

Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain-Heart Interrelationship for Improved Patient Outcomes.

The pathophysiological mechanisms underlying severe cardiac dysfunction after aneurysmal subarachnoid haemorrhage (aSAH) remain poorly understood. In the present study, we focused on two categories of contributing factors describing the brain-heart relationship. The first group includes brain-specific cerebrospinal fluid (CSF) and serum biomarkers, as well as cardiac-specific biomarkers. The secondary category encompasses parameters associated with cerebral autoregulation and the autonomic nervous system. A group of 15 aSAH patients were included in the analysis. Severe cardiac complications were diagnosed in seven (47%) of patients. In the whole population, a significant correlation was observed between CSF S100 calcium-binding protein B (S100B) and brain natriuretic peptide (BNP) (rS = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (rS = 0.57; p = 0.025) and BNP (rS = 0.66; p = 0.029), as well as between CSF tau protein and BNP (rS = 0.78; p = 0.039). Patients experiencing severe cardiac complications exhibited notably higher levels of serum tau protein at day 1 (0.21 ± 0.23 [ng/mL]) compared to those without severe cardiac complications (0.03 ± 0.04 [ng/mL]); p = 0.009. Impaired cerebral autoregulation was noted in patients both with and without severe cardiac complications. Elevated serum NSE at day 1 was related to impaired cerebral autoregulation (rS = 0.90; p = 0.037). On the first day, a substantial, reciprocal correlation between heart rate variability low-to-high frequency ratio (HRV LF/HF) and both GFAP (rS = -0.83; p = 0.004) and S100B (rS = -0.83; p = 0.004) was observed. Cardiac and brain-specific biomarkers hold the potential to assist clinicians in providing timely insights into cardiac complications, and therefore they contribute to the prognosis of outcomes.

The Role of Early Serum Biomarkers and Clinical Rating Scales in the Prediction of Delayed Cerebral Ischaemia and Short-Term Outcome after Aneurysmal Subarachnoid Haemorrhage: Single Centre Experience.

Considering the variety of complications that arise after aneurysmal subarachnoid haemorrhage (aSAH) and the complex pathomechanism of delayed cerebral ischaemia (DCI), the task of predicting the outcome assumes a profound complexity. Therefore, there is a need to develop early predictive and decision-making models. This study explores the effect of serum biomarkers and clinical scales on patients' outcomes and their interrelationship with DCI and systemic complications in aSAH. This was a retrospective analysis including aSAH patients admitted to the Wroclaw University Hospital (Wroclaw, Poland) from 2011 to 2020. A good outcome was defined as a modified Rankin Scale (mRS) score of 0-2. The prediction of the development of DCI and poor outcome was conducted using logistic regression as a standard model (SM) and random forest as a machine learning method (ML). A cohort of 174 aSAH patients were included in the analysis. DCI was diagnosed in 79 (45%) patients. Significant differences between patients with poor vs. good outcome were determined from their levels of albumin (31 ± 7 vs. 35 ± 5 (g/L); p < 0.001), D-dimer (3.0 ± 4.5 vs. 1.5 ± 2.8 (ng/mL); p < 0.001), procalcitonin (0.2 ± 0.4 vs. 0.1 ± 0.1 (ng/mL); p < 0.001), and glucose (169 ± 69 vs. 137 ± 48 (nmol/L); p < 0.001). SM for DCI prediction included the Apache II scale (odds ratio [OD] 1.05; 95% confidence interval [CI] 1.00-1.09) and albumin level (OD 0.88; CI 0.82-0.95). ML demonstrated that low albumin level, high Apache II scale, increased D-dimer and procalcitonin levels had the highest predictive values for DCI. The integration of clinical parameters and scales with a panel of biomarkers may effectively facilitate the stratification of aSAH patients, identifying those at high risk of secondary complications and poor outcome.

Citrulline, Intestinal Fatty Acid-Binding Protein and the Acute Gastrointestinal Injury Score as Predictors of Gastrointestinal Failure in Patients with Sepsis and Septic Shock.

Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.

Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets.

Hospital mortality in sepsis varies between 30-45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1ß maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1ß. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1ß form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1ß processing.

The NUTRIC Score as a Tool to Predict Mortality and Increased Resource Utilization in Intensive Care Patients with Sepsis.

The Nutrition Risk in Critically Ill score (NUTRIC) is an important nutritional risk assessment instrument for patients in the intensive care unit (ICU). The purpose of this study was to evaluate the power of the score to predict mortality in patients treated for sepsis and to forecast increased resource utilization and nursing workload in the ICU. The NUTRIC score predicted mortality (AUC 0.833, p < 0.001) with the optimal cut-off value of 6 points. Among patients with a score ≥ 6 on ICU admission, the 28-day mortality was 61%, and 10% with a score < 6 (p < 0.001). In addition, a NUTRIC score of ≥6 was associated with a more intense use of ICU resources, as evidenced by a higher proportion of patients requiring vasopressor infusion (98 vs. 82%), mechanical ventilation (99 vs. 87%), renal replacement therapy (54 vs. 26%), steroids (68 vs. 31%), and blood products (60 vs. 43%); the nursing workload was also significantly higher in this group. In conclusion, the NUTRIC score obtained at admission to the ICU provided a good discriminative value for mortality and makes it possible to identify patients who will ultimately require intense use of ICU resources and an associated increase in the nursing workload during treatment.

Cerebral Autoregulation, Cerebral Hemodynamics, and Injury Biomarkers, in Patients with COVID-19 Treated with Veno-Venous Extracorporeal Membrane Oxygenation.

BACKGROUND: This study aimed to describe the cerebrovascular dynamics, in particular cerebral autoregulation (CA), and cerebral biomarkers as neuron-specific enolase (NSE) in patients with a diagnosis of coronavirus disease 2019 and acute respiratory distress syndrome as well as undergoing veno-venous extracorporeal membrane treatment. METHODS: This was a single center, observational study conducted in the intensive care unit of the University Hospital in Wroclaw from October 2020 to February 2022. Transcranial Doppler recordings of the middle cerebral artery conducted for at least 20 min were performed. Cerebral autoregulation (CA) was estimated by using the mean velocity index (Mxa), calculated as the moving correlation coefficient between slow-wave oscillations in cerebral blood flow velocity and arterial blood pressure. Altered CA was defined as a positive Mxa. Blood samples for the measurement of NSE were obtained at the same time as transcranial Doppler measurements. RESULTS: A total of 16 patients fulfilled the inclusion criteria and were enrolled in the study. The median age was 39 (34-56) years. Altered CA was found in 12 patients, and six out of seven patients who died had altered CA. A positive Mxa was a significant predictor of mortality, with a sensitivity of 85.7%. We found that three out of five patients with pathological changes in brain computed tomography and six out of ten patients with neurological complications had altered CA. NSE was a significant predictor of mortality (cutoff value: 28.9 µg/L); area under the curve = 0.83, p = 0.006), with a strong relationship between increased level of NSE and altered CA, χ2 = 6.24; p = 0.035; φ = 0.69. CONCLUSIONS: Patients with coronavirus disease 2019-related acute respiratory distress syndrome, requiring veno-venous extracorporeal membrane treatment, are likely to have elevated NSE levels and altered CA. The CA was associated with NSE values in this group. This preliminary analysis suggests that advanced neuromonitoring and evaluation of biomarkers should be considered in this population.

Fluid resuscitation, but not inhaled nitric oxide, improves microcirculation in septic pigs.

BACKGROUND: Prolonged deterioration of microvascular flow during sepsis leads to organ dysfunction. Capillary flow restoration may prevent this complication. OBJECTIVES: The main aim of this study was to investigate the microcirculatory effects of inhaled nitric oxide (iNO) combined with intravenous hydrocortisone in a porcine model of sepsis. The 2nd aim was to evaluate the influence of hemodynamic resuscitation with noradrenaline and crystalloids on capillary flow. MATERIAL AND METHODS: Eleven piglets of Polish breed underwent surgical colon perforation to develop sepsis. They were randomly allocated to one of 3 treatment groups. Group 1 received iNO and hydrocortisone, whereas group 2 did not. Both groups were resuscitated with crystalloids and noradrenaline if hypotensive. Group 3 received no treatment at all. During a 30-hour observation, we assessed the microcirculation using sidestream dark field imaging (SDF). RESULTS: We found no effect of iNO with hydrocortisone on the microcirculation. Fluid and vasopressor treatment led to a higher microcirculatory flow index after 20 h of observation (3 and 2.75 in groups 1 and 2 compared to 1.9 in group 3), a greater proportion of perfused vessels (94% and 87% compared to 63% in groups 1, 2 and 3, respectively) and a greater perfused vessel density (15.2 mm/mm2, 15.09 mm/mm2 and 10.1 mm/mm2 in groups 1, 2 and 3, respectively). CONCLUSIONS: Crystalloid and vasopressor treatment postponed microvascular flow derangements, whereas iNO combined with intravenous hydrocortisone did not improve microvascular perfusion.

Intestinal Fatty Acid Binding Protein (I-FABP) as a Prognostic Marker in Critically Ill COVID-19 Patients.

Gastrointestinal symptoms are common in critically ill COVID-19 patients. There is currently no generally recognized method of assessing gastrointestinal injury in unconscious or sedated intensive care unit (ICU) patients. I-FABP (intestinal fatty acid binding protein) and citrulline have previously been studied as potential biomarkers of enterocyte damage in various gastrointestinal tract diseases, and changes in the levels of these markers may reflect intestinal wall damage in COVID-19. Patients with critical COVID-19, with diagnosed sepsis, or septic shock requiring ICU treatment were included in the study. Blood samples for citrulline and I-FABP were taken daily from day 1 to 5. I-FABP levels were significantly higher in patients who eventually died from COVID-19 than in survivors, and the optimal I-FABP cut-off point for predicting 28-day mortality was 668.57 pg/mL (sensitivity 0.739, specificity 0.765). Plasma levels of I-FABP, but not citrulline, were associated with significantly higher mortality and appeared to be a predictor of poor outcome in multivariate logistic regression analysis. In conclusion, I-FABP seems to be an effective prognostic marker in critically ill COVID-19 patients. Assessing mortality risk based on intestinal markers may be helpful in making clinical decisions regarding the management of intestinal injury, imaging diagnostics, and potential surgical interventions.

Transcutaneous electrical acupoint stimulation to reduce opioid consumption in patients undergoing inguinal hernia repair: protocol for a randomized controlled trial.

BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) in the postoperative treatment of patients undergoing inguinal hernia repair compared with sham and no treatment group. METHODS: This study is a protocol for a three-armed, single-blinded, placebo-controlled randomized controlled trial. Ninety participants scheduled for inguinal hernia repair will be randomly assigned to the TEAS group (n = 30), sham group (n = 30), and control group (n = 30). The TEAS group will receive treatment using four portable coin-sized electro-stimulators at both local and distal acupuncture points. The sham group will receive sham treatment with mock electrostimulation. The treatment groups will receive mixed frequency stimulation (alternating at 2 and 100 Hz every 3 s) in continuous mode for 30 min at intervals of 2 h for 24 h postoperatively. The control group will receive postoperative pain control using patient-controlled analgesia (PCA) device. The primary outcome is the total morphine dose received in the postoperative period (mg) using PCA 24 h after surgery. The number of PCA demands (i.e., times the button will be pressed) and delivered bolus doses, score on the Visual Analogue Scale, opioid-related side effects, the requirement for supplemental medications, score on the Hospital Anxiety and Depression Scale (HADS), and blood levels of stress hormones cortisol and prolactin. DISCUSSION: The results of this trial will determine whether TEAS with intensified stimulation protocol is a safe and effective option for reducing analgesic consumption and postoperative pain. TRIAL REGISTRATION: ISRCTN76428396. Registered on 05 October 2020. https://www.isrctn.com/ISRCTN76428396.

Explainable Artificial Intelligence Helps in Understanding the Effect of Fibronectin on Survival of Sepsis.

Fibronectin (FN) plays an essential role in the host's response to infection. In previous studies, a significant decrease in the FN level was observed in sepsis; however, it has not been clearly elucidated how this parameter affects the patient's survival. To better understand the relationship between FN and survival, we utilized innovative approaches from the field of explainable machine learning, including local explanations (Break Down, Shapley Additive Values, Ceteris Paribus), to understand the contribution of FN to predicting individual patient survival. The methodology provides new opportunities to personalize informative predictions for patients. The results showed that the most important indicators for predicting survival in sepsis were INR, FN, age, and the APACHE II score. ROC curve analysis showed that the model's successful classification rate was 0.92, its sensitivity was 0.92, its positive predictive value was 0.76, and its accuracy was 0.79. To illustrate these possibilities, we have developed and shared a web-based risk calculator for exploring individual patient risk. The web application can be continuously updated with new data in order to further improve the model.

Compartment-Specific Differences in the Activation of Monocyte Subpopulations Are Not Affected by Nitric Oxide and Glucocorticoid Treatment in a Model of Resuscitated Porcine Endotoxemic Shock.

Inhaled nitric oxide (iNO) remains one of the treatment modalities in shock, and in addition to its vasoactive properties, iNO exerts immunomodulatory effects. We used a porcine model of endotoxemia with shock resuscitation (control) and additional treatment with iNO and a steroid (treatment group). After 20 h, bone marrow (BM), peripheral blood (PB), and bronchoalveolar lavage fluid (BALF) were collected to analyze the immunophenotype and mitochondrial membrane potential (Δφ) in three subsets of monocytes. In both groups, SLA-DR expression decreased twofold on the circulating CD14+CD163+ and CD14−CD163+ monocytes, while it did not change on the CD14+CD163+. Δφ increased only in the CD14−CD163+ subpopulation (0.8 vs. 2.0, p < 0.001). The analysis of compartment-specific alterations showed that nearly 100% of BALF CD14+CD163+ and CD14−CD163+ monocytes expressed SLA-DR, and it was higher compared to PB (32% and 20%, p < 0.0001) and BM (93% and 67%, p < 0.001, respectively) counterparts. BALF CD14+CD163+ had a threefold higher Δφ than PB and BM monocytes, while the Δφ of the other subsets was highest in PB monocytes. We confirmed the compartmentalization of the monocyte response during endotoxemic shock, which highlights the importance of studying tissue-resident cells in addition to their circulating counterparts. The iNO/steroid treatment did not further impair monocyte fitness.

Inflammasome-related Markers upon ICU Admission do not Correlate with Outcome in Critically Ill COVID-19 Patients.

PURPOSE: The development of targeted biological therapies for coronavirus disease 2019 (COVID-19) requires reliable biomarkers that could help indicate how patients are responding. The hyperactivation of inflammasomes by the SARS-CoV2 virus is hypothesized to contribute to a more severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins upon admission to the intensive care unit (ICU). PATIENTS AND METHODS: We performed a prospective cohort study. Plasma samples were obtained from 45 critically ill COVID-19 patients and 10 patients without any signs of infection (traumatic brain injury [TBI]) on admission to the ICU. Concentrations of IL-1a, IL-1ß, IL-18, IL-1RA, galectin-1, apoptosis-associated speck-like proteins, LDH, ferritin, and gasdermin D were analyzed. A cell-free caspase-1 plasma assay was done by inhibitor-based immunoprecipitation followed by a Western Blot. Demographic and clinical characteristics were recorded. RESULTS: Inhospital mortality in COVID-19 patients was 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 pg/mL vs. 30764.20 pg/mL, P = 0.007), but other inflammasome-related biomarkers had similar concentrations. Patients with a Sequential Organ Failure Assessment (SOFA) score of > 9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison with low-risk patients (25551.3 pg/mL vs. 16302.7 pg/mL, P = 0.014; 14.5 pg/mL vs. 39.4pg/mL, P = 0.04, respectively). Statistically significant correlations were observed between: IL-1a and platelets (r = -0.37), IL-1 ß and platelets (r = -0.36), ferritin and INR (r = 0.39). Activated caspase-1 p35, whose presence was related to higher fibrinogen and lower D-dimers, was detected in 12 out of 22 COVID-19 patients and in none of the TBI patients. Moreover, densitometric analysis showed a significantly higher amount of p35 in patients with a SOFA score > 9. CONCLUSION: We found that the systemic markers of activation of inflammasomes in critically ill COVID-19 patients were not directly related to outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

Extracorporeal membrane oxygenation for severe COVID-19-associated acute respiratory distress syndrome in Poland: a multicenter cohort study.

BACKGROUND: In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. METHODS: This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. RESULTS: There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). CONCLUSIONS: The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.

Changes in autonomic nervous system during cerebral desaturation episodes in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Little evidence is available on the effect of regional cerebral desaturation (rCD) episodes that occur in the first days after aneurysm subarachnoid haemorrhage (aSAH) on the autonomic nervous system activity and on cardiovascular hemodynamics. In this study, we aimed to determine the impact of rCD episodes, developed within 5 days of aSAH, on the autonomic nervous system based on the assessment of baroreflex sensitivity (BRS) and on cardiac output (CO) and cardiac index (CI), and on cerebral autoregulation (CA). MATERIALS AND METHODS: Of 96 patients with aSAH, 36 patients (aged 57 (48-69)) met the inclusion criteria and were included in the study. Regional cerebral oxygen saturation and rCD episodes were evaluated using near-infrared spectroscopy. CA was quantified by the correlation coefficient (TOxa). Cardiac output (CO) and cardiac index (CI) were monitored using the FloTrack®/EV1000. Baroreflex sensitivity (BRS) was assessed using the cross-correlation method. Scores of 1 to 3 in Glasgow Outcome Scale were classified as a poor outcome. RESULTS: During episodes of rCD, BRS decreased significantly compared to baseline (p = 0.027) in patients who had a total duration of rCD episodes of more than 10 hours. During rCD episodes, CA improved slightly in comparison to baseline (p = 0.027). The threshold associated with poor outcome was: rSO2 < 62% (p = 0.002). CONCLUSIONS: BRS decreased in patients who had a total duration rCD episodes of more than 10 hours within the 5 days of aSAH. These results might partly explain the relationship between lower BRS and worse prognosis.

Soluble Urokinase-Type Plasminogen Activator Receptor Levels as a Predictor of Kidney Replacement Therapy in Septic Patients with Acute Kidney Injury: An Observational Study.

The soluble urokinase-type plasminogen activator receptor (suPAR) is involved in the pathogenesis of acute kidney injury (AKI). Our goal was to establish the optimal suPAR cut-off point for predicting the need for kidney replacement therapy (KRT) use in sepsis patients and to analyze survival rates based on the suPAR level, AKI diagnosis, and the requirement for KRT. In total, 51 septic patients were included (82% septic shock; 96% mechanically ventilated, 35% KRT). Patients were stratified according to the AKI diagnosis and the need for KRT into three groups: AKI(+)/KRT(+), AKI(+)/KRT(−), and AKI(−)/KRT(−). A control group (N = 20) without sepsis and kidney failure was included. Sepsis patients had higher levels of the suPAR than control (13.01 vs. 4.05 ng/mL, p < 0.001). On ICU admission, the suPAR level was significantly higher in the AKI(+)/KRT(+) group than in the AKI(+)/KRT(−) and AKI(−)/KRT(−) groups (18.5 vs. 10.6 and 9.5 ng/mL, respectively; p = 0.001). The optimal suPAR cut-off point for predicting the need for KRT was established at 10.422 ng/mL (area under the curve 0.801, sensitivity 0.889, specificity 0.636). Moreover, patients AKI(+)/KRT(+) had the lowest probability of survival compared to patients AKI(+)/KRT(−) and AKI(−)/KRT(−) (p = 0.0003). The results indicate that the suPAR measurements may constitute an important element in the diagnosis of a patient with sepsis.