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Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis ( p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.

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., (© 2024 Barbara Adamik et al., published by Sciendo.)

One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50% male) was divided into a group of 274 patients receiving any AP prior to COVID-19 infection (AP group), and after propensity score matching, a group of 274 patients without previous AP (non-AP group). Patients from the AP group were less frequently hospitalized in the intensive care unit: 9% vs. 15%, 0.55 (0.33-0.94), developed less often shock: 9% vs. 15%, 0.56 (0.33-0.96), and required less aggressive forms of therapy. The AP group had more coronary revascularizations: 5% vs. 1%, 3.48 (2.19-5.55) and strokes/TIA: 5% vs. 1%, 3.63 (1.18-11.2). The bleeding rate was comparable: 7% vs. 7%, 1.06 (0.54-2.06). The patients from the AP group had lower 3-month mortality: 31% vs. 39%, 0.69 (0.51-0.93) and didn't differ significantly in 6-month mortality: 34% vs. 41%, 0.79 (0.60-1.04). When analyzing the subgroup with a history of myocardial infarction and/or coronary revascularization and/or previous stroke/transient ischemic attack and/or peripheral artery disease, AP had a beneficial effect on both 3-month: 37% vs. 56%, 0.58 (0.40-0.86) and 6-month mortality: 42% vs. 57%, 0.63 (0.44-0.92). Moreover, the favourable effect was highly noticeable in this subgroup where acetylsalicylic acid was continued during hospitalization with reduction of in-hospital: 19% vs. 43%, 0.31 (0.15-0.67), 3-month: 30% vs. 54%, 044 (0.26-0.75) and 6-month mortality: 33% vs. 54%, 0.49 (0.29-0.82) when confronted with the subgroup who had acetylsalicylic acid suspension during hospitalization. The AP may have a beneficial impact on hospital course and mortality in COVID-19 and shouldn't be discontinued, especially in high-risk patients., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2023. The Author(s).)

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) (r S = 0.62; p = 0.040). Additionally, we identified a significant correlation between CSF neuron-specific enolase (NSE) with cardiac troponin I (r S = 0.57; p = 0.025) and BNP (r S = 0.66; p = 0.029), as well as between CSF tau protein and BNP (r S = 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 (r S = 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 (r S = -0.83; p = 0.004) and S100B (r S = -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.

Advanced age is known to be a predictor with COVID-19 severity. Understanding of other disease progression factors may shorten the time from patient admission to applied treatment. The Veterans Health Administration COVID-19 (VACO index) was assumed to additionally anticipate clinical results of patients hospitalized with a proven infection caused by the SARS-CoV-2 virus., Methods: The medical records of 2183 hospitalized patients were retrospectively analyzed. Patients were divided into four risk-of-death categories: low risk, medium risk, high-risk, and extreme risk depending on their VACO index calculation., Results: Significant differences in the mortality at the hospital after three months of discharge and six months after discharge were noticed. For the patients in the extreme-risk group, mortality reached 37.42%, 62.81%, and 78.44% for in-hospital, three months of discharge, and six months of discharge, respectively. The mortality marked as high risk reached 20.38%, 37.19%, and 58.77%. Moreover, the secondary outcomes analysis acknowledged that patients classified as extreme risk were more likely to suffer from cardiogenic shock, myocardial infarction, myocardial injury, stroke, pneumonia, acute kidney injury, and acute liver dysfunction. Patients at moderate risk were more often admitted to ICU when compared to other patients., Conclusions: The usage of the VACO index, combined with an appropriate well-defined medical interview and past medical history, tends to be a helpful instrument in order to predict short-term mortality and disease progression based on previous medical records.

Background: Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19)., Methods: This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed., Results: We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m 2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097)., Conclusions: The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Konikowska, Kiliś-Pstrusińska, Matera-Witkiewicz, Kujawa, Adamik, Doroszko, Kaliszewski, Pomorski, Protasiewicz, Sokołowski, Madziarska and Jankowska.)

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-1β 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-1β. 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-1β 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-1β processing., (© 2023. The Author(s).)

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.

Background: Sodium imbalance is one of the most common electrolyte disturbances encountered in the medical practice, and it may present with either hyponatremia or hypernatremia. Both sodium abnormalities are related with unfavorable outcomes., Objective: Elucidation of the prevalence of dysnatremia among COVID-19 patients and its impact on 30- and 90-day mortality and need for ICU admission was the goal., Design and Participants: A single-center, retrospective, observational study was conducted. A total of 2026 adult, SARS-CoV-2 positive patients, admitted to Wroclaw University Hospital between 02.2020 and 06.2021, were included. On admission, patients were divided into groups: normonatremic (N), hyponatremic (L), and hypernatremic (H). Acquired data was processed, and Cox hazards regression and logistic regression were implemented., Key Results: Hyponatremia on admission occurred in 17.47% ( n = 354) of patients and hypernatremia occurred in 5.03% ( n = 102). Dysnatremic patients presented with more comorbidities, used more drugs, and were statistically more often admitted to the ICU. Level of consciousness was the strongest predictor of ICU admission (OR = 1.21, CI: 1.16-1.27, p < 0.001). Thirty-day mortality was significantly higher in both the L and H groups (28.52%, p = 0.0001 and 47.95%, p < 0.0001, respectively), in comparison to 17.67% in the N group. Ninety-day mortality showed a similar trend in all study groups: 34.37% in the L group ( p = 0.0001), 60.27% ( p < 0.0001) in the H group, and 23.32% in the N group. In multivariable analyses, hypo- and hypernatremia were found to be independent predictors of 30- and 90-day mortality., Conclusions: Both hypo- and hypernatremia are strong predictors of mortality and disease severity in COVID-19 patients. Extraordinary care should be taken when dealing with hypernatremic, COVID-positive patients, as this group exhibits the highest mortality rates.

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.

Background: Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital and the risk of later death in cancer patients with COVID-19., Methods: The study included patients with a reported history of malignant tumor ( n = 151) and a control group with no history of cancer ( n = 151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models., Results: Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients' admission were linked to significantly increased risk of death. They are: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophils., Conclusion: Early identification of the indicators of a poorer prognosis may serve clinicians in better tailoring surveillance or treatment among cancer patients with COVID-19.

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.

Background: The COVID-GRAM is a clinical risk rating score for predicting the prognosis of hospitalized COVID-19 infected patients., Aim: Our study aimed to evaluate the use of the COVID-GRAM score in patients with COVID-19 based on the data from the COronavirus in the LOwer Silesia (COLOS) registry., Material and Methods: The study group (834 patients of Caucasian patients) was retrospectively divided into three arms according to the risk achieved on the COVID-GRAM score calculated at the time of hospital admission (between February 2020 and July 2021): low, medium, and high risk. The Omnibus chi-square test, Fisher test, and Welch ANOVA were used in the statistical analysis. Post-hoc analysis for continuous variables was performed using Tukey's correction with the Games-Howell test. Additionally, the ROC analysis was performed over time using inverse probability of censorship (IPCW) estimation. The GRAM-COVID score was estimated from the time-dependent area under the curve (AUC)., Results: Most patients (65%) had a low risk of complications on the COVID-GRAM scale. There were 113 patients in the high-risk group (13%). In the medium- and high-risk groups, comorbidities occurred statistically significantly more often, e.g., hypertension, diabetes, atrial fibrillation and flutter, heart failure, valvular disease, chronic kidney disease, and obstructive pulmonary disease (COPD), compared to low-risk tier subjects. These individuals were also patients with a higher incidence of neurological and cardiac complications in the past. Low saturation of oxygen values on admission, changes in C-reactive protein, leukocytosis, hyperglycemia, and procalcitonin level were associated with an increased risk of death during hospitalization. The troponin level was an independent mortality factor. A change from low to medium category reduced the overall survival probability by more than 8 times and from low to high by 25 times. The factor with the strongest impact on survival was the absence of other diseases. The medium-risk patient group was more likely to require dialysis during hospitalization. The need for antibiotics was more significant in the high-risk group on the GRAM score., Conclusion: The COVID-GRAM score corresponds well with total mortality. The factor with the strongest impact on survival was the absence of other diseases. The worst prognosis was for patients who were unconscious during admission. Patients with higher COVID-GRAM score were significantly less likely to return to full health during follow-up. There is a continuing need to develop reliable, easy-to-adopt tools for stratifying the course of SARS-CoV-2 infection.

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases ( n = 2), whereas 92% of cases were negative ( n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted ( n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.

Background: Even though coronary artery disease (CAD) is considered an independent risk factor of an unfavorable outcome of SARS-CoV-2-infection, the clinical course of COVID-19 in subjects with CAD is heterogeneous, ranging from clinically asymptomatic to fatal cases. Since the individual C 2 HEST components are similar to the COVID-19 risk factors, we evaluated its predictive value in CAD subjects., Materials and Methods: In total, 2183 patients hospitalized due to confirmed COVID-19 were enrolled onto this study consecutively. Based on past medical history, subjects were assigned to one of two of the study arms ( CAD vs. non-CAD ) and allocated to different risk strata, based on the C 2 HEST score., Results: The CAD cohort included 228 subjects, while the non-CAD cohort consisted of 1956 patients. In-hospital , 3-month and 6-month mortality was highest in the high-risk C 2 HEST stratum in the CAD cohort, reaching 43.06%, 56.25% and 65.89%, respectively, whereas in the non-CAD cohort in the high-risk stratum, it reached: 26.92%, 50.77% and 64.55%. Significant differences in mortality between the C 2 HEST stratum in the CAD arm were observed in post hoc analysis only for medium- vs. high-risk strata. The C 2 HEST score in the CAD cohort could predict hypovolemic shock, pneumonia and acute heart failure during hospitalization, whereas in the non-CAD cohort, it could predict cardiovascular events (myocardial injury, acute heart failure, myocardial infract, carcinogenic shock), pneumonia, acute liver dysfunction and renal injury as well as bleedings., Conclusions: The C 2 HEST score is a simple, easy-to-apply tool which might be useful in risk stratification, preferably in non-CAD subjects admitted to hospital due to COVID-19.

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.

Deviations in laboratory tests assessing liver function in patients with COVID-19 are frequently observed. Their importance and pathogenesis are still debated. In our retrospective study, we analyzed liver-related parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), albumin, comorbidities and other selected potential risk factors in patients admitted with SARS-CoV-2 infection to assess their prognostic value for intensive care unit admission, mechanical ventilation necessity and mortality. We compared the prognostic effectiveness of these parameters separately and in pairs to the neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of in-hospital mortality, using the Akaike Information Criterion (AIC). Data were collected from 2109 included patients. We created models using a sample with complete laboratory tests n = 401 and then applied them to the whole studied group excluding patients with missing singular variables. We estimated that albumin may be a better predictor of the COVID-19-severity course compared to NLR, irrespective of comorbidities (p < 0.001). Additionally, we determined that hypoalbuminemia in combination with AST (OR 1.003, p = 0.008) or TBIL (OR 1.657, p = 0.001) creates excellent prediction models for in-hospital mortality. In conclusion, the early evaluation of albumin levels and liver-related parameters may be indispensable tools for the early assessment of the clinical course of patients with COVID-19.

Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968−1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518−1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury.

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.

The SARS-CoV-2 virus alters the expression of genes for extracellular matrix proteins, including fibronectin. The aim of the study was to establish the relationship between different forms of fibronectin, such as plasma (pFN), cellular (EDA-FN), and proteolytic FN-fragments, and disease severity and mortality of critically ill patients treated in the intensive care unit. The levels of pFN, EDA-FN, and FN-fragments were measured in patients with a viral (N = 43, COVID-19) or bacterial (N = 41, sepsis) infection, using immunoblotting and ELISA. The level of EDA-FN, but not pFN, was related to the treatment outcome and was significantly higher in COVID-19 Non-survivors than in Survivors. Furthermore, EDA-FN levels correlated with APACHE II and SOFA scores. FN-fragments were detected in 95% of COVID-19 samples and the amount was significantly higher in Non-survivors than in Survivors. Interestingly, FN-fragments were present in only 56% of samples from patients with bacterial sepsis, with no significant differences between Non-survivors and Survivors. The new knowledge gained from our research will help to understand the differences in immune response depending on the etiology of the infection. Fibronectin is a potential biomarker that can be used in clinical settings to monitor the condition of COVID-19 patients and predict treatment outcomes.

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-1β, 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 β 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Gastrointestinal manifestations may accompany the respiratory symptoms of COVID-19. Abdominal pain (AP) without nausea and vomiting is one of the most common. To date, its role and prognostic value in patients with COVID-19 is still debated. Therefore, we performed a retrospective analysis of 2184 individuals admitted to hospital due to COVID-19. We divided the patients into four groups according to presented symptoms: dyspnea, n = 871 (39.9%); AP, n = 97 (4.4%); AP with dyspnea together, n = 50 (2.3%); and patients without dyspnea and AP, n = 1166 (53.4%). The patients with AP showed tendency to be younger than these with dyspnea, but without AP (63.0 [38.0−70.0] vs. 65.0 [52.0−74.0] years, p = 0.061), and they were more often females as compared to patients with dyspnea (57.7% vs. 44.6%, p = 0.013, for females). Patients with AP as a separate sign of COVID-19 significantly less often developed pneumonia as compared to individuals with dyspnea or with dyspnea and AP together (p < 0.0001). Patients with AP or AP with dyspnea were significantly less frequently intubated or transferred to the intensive care unit (p = 0.003 and p = 0.031, respectively). Individuals with AP alone or with dyspnea had significantly lower rate of mortality as compared to patients with dyspnea (p = 0.003). AP as a separate symptom and also as a coexisting sign with dyspnea does not predispose the patients with COVID-19 to the worse clinical course and higher mortality.

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.

Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C 2 HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C 2 HEST score result. The measured outcomes included: in-hospital -mortality, three-month- and six-month- all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C 2 HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C 2 HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C 2 HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C 2 HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.

Senility has been identified among the strongest risk predictors for unfavorable COVID-19-outcome. However, even in the elderly population, the clinical course of infection in individual patients remains unpredictable. Hence, there is an urgent need for developing a simple tool predicting adverse COVID-19-outcomes. We assumed that the C2HEST-score could predict unfavorable clinical outcomes in the elderly subjects with COVID-19-subjects., Methods: We retrospectively analyzed 1047 medical records of patients at age > 65 years, hospitalized at the medical university center due to COVID-19. Subsequently, patients were divided into three categories depending on their C2HEST-score result., Results: We noticed significant differences in the in-hospital and 3- month and 6- month mortality-which was the highest in high - risk -C2HEST-stratum reaching 35.7%, 54.4%, and 65.9%, respectively. The medium-risk -stratum mortalities reached 24.1% 43.4%, and 57.6% and for low-risk -stratum 14.4%, 25.8%, and 39.2% respectively. In the C2HEST-score model, a change from the low to the medium category increased the probability of death intensity approximately two-times. Subsequently, transfer from the low-risk to the high-risk -stratum raised all-cause-death-intensity 2.7-times. Analysis of the secondary outcomes revealed that the C2HEST-score has predictive value for acute kidney injury, acute heart failure, and cardiogenic shock., Conclusions: C2HEST-score analysis on admission to the hospital may predict the mortality, acute kidney injury, and acute heart failure in elderly subjects with COVID-19.

Background: Diabetes mellitus is among the most frequent comorbidities worsening COVID-19 outcome. Nevertheless, there are no data regarding the optimal risk stratification of patients with diabetes and COVID-19. Since individual C 2 HEST components reflect the comorbidities, we assumed that the score could predict COVID-19 outcomes., Material and Methods: A total of 2184 medical records of patients hospitalized for COVID-19 at the medical university center were analyzed, including 473 diabetic patients and 1666 patients without any glucose or metabolic abnormalities. The variables of patients' baseline characteristics were retrieved to calculate the C 2 HEST score and subsequently the diabetic and non-diabetic subjects were assigned to the following categories: low-, medium- or high-risk. The measured outcomes included: in-hospital mortality; 3-month and 6-month all-cause mortality; non-fatal end of hospitalization (discharged home/sudden-deterioration/rehabilitation) and adverse in-hospital clinical events., Results: A total of 194 deaths (41%) were reported in the diabetic cohort, including 115 in-hospital deaths (24.3%). The 3-month and 6-month in-hospital mortality was highest in the high-risk C 2 HEST stratum. The C 2 HEST score revealed to be more sensitive in non-diabetic-group. The estimated six-month survival probability for high-risk subjects reached 0.4 in both cohorts whereas for the low-risk group, the six-month survival probability was 0.7 in the diabetic vs. 0.85 in the non-diabetic group-levels which were maintained during whole observation period. In both cohorts, receiver operating characteristics revealed that C 2 HEST predicts the following: cardiogenic shock; acute heart failure; myocardial injury; and in-hospital acute kidney injury., Conclusions: We demonstrated the usefulness and performance of the C 2 HEST score in predicting the adverse COVID-19 outcomes in hospitalized diabetic subjects.

The coronavirus disease 2019 (COVID-19) shows high incidence of thromboembolic events in humans. In the present study, we aimed to evaluate if anticoagulation prior to COVID-19 infection may impact clinical profile, as well as mortality rate among patients hospitalized with COVID-19. The study was based on retrospective analysis of medical records of patients with laboratory confirmed SARS-CoV-2 infection. After propensity score matching (PSM), a group of 236 patients receiving any anticoagulant treatment prior to COVID-19 infection (AT group) was compared to 236 patients without previous anticoagulation (no AT group). In 180 days, the observation we noted comparable mortality rate in AT and no AT groups (38.5% vs. 41.1%, p = 0.51). Similarly, we did not observe any statistically significant differences in admission in the intensive care unit (14.1% vs. 9.6%, p = 0.20), intubation and mechanical ventilation (15.0% vs. 11.6%, p = 0.38), catecholamines usage (14.3% vs. 13.8%, p = 0.86), and bleeding rate (6.3% vs. 8.9%, p = 0.37) in both groups. Our results suggest that antithrombotic treatment prior to COVID-19 infection is unlikely to be protective for morbidity and mortality in patients hospitalized with COVID-19.

Background: Patients with heart failure (HF) are at high risk of unfavorable courses of COVID-19. The aim of this study was to evaluate characteristics and outcomes of COVID-19 patients with HF., Methods: Data of patients hospitalized in a tertiary hospital in Poland between March 2020 and May 2021 with laboratory-confirmed COVID-19 were analyzed. The study population was divided into a HF group (patients with a history of HF) and a non-HF group., Results: Out of 2184 patients (65 ± 13 years old, 50% male), 12% had a history of HF. Patients from the HF group were older, more often males, had more comorbidities, more often dyspnea, pulmonary and peripheral congestion, inflammation, and end-organ damage biomarkers. HF patients had longer and more complicated hospital stay, with more frequent acute HF development as compared with non-HF. They had significantly higher mortality assessed in hospital (35% vs. 12%) at three (53% vs. 22%) and six months (72% vs. 47%). Of 76 (4%) patients who developed acute HF, 71% died during hospitalization, 79% at three, and 87% at six months., Conclusions: The history of HF identifies patients with COVID-19 who are at high risk of in-hospital complications and mortality up to six months of follow-up.

The disease caused by coronavirus SARS-CoV-2 (COVID-19) can affect almost all organs of the human body, including kidneys. We conducted a one-center study to comprehensively analyze the effects of kidney involvement on the course and outcomes in patients hospitalized with COVID-19, depending on the estimated glomerular filtration rate (eGFR) at admission. Out of the 1958 patients, 1342 (68.54%) had eGFR ≥ 60 mL/min/1.73 m 2 (group A) and 616 (31.46%) had eGFR < 60 mL/min/1.73 m 2 (group B). Group B was additionally divided into subgroups B1, B2, and B3 based on eGFR. We found that mortality rates during hospitalization, as well as after 90 and 180 days, were much higher in group B than group A. The highest mortality was observed in the B2 subgroup with eGFR of 15-29. The mortality of B patients was associated with comorbidities, respiratory dysfunction, immunological impairment, and more frequent development of AKI. AKI had a negative impact on patients' survival, regardless of the initial renal function. At discharge, 7.4% of patients had serum creatinine levels 30% higher, or more, as compared to admission. The disease course and outcomes in COVID-19 patients are associated with baseline eGFR; however, AKI during hospitalization is a more significant predictor of poor prognosis regardless of the initial renal function.

Background: In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support., Methods: This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn-winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated., Results: Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO 2 R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU., Conclusion: A substantial number of influenza infections occurred in the autumn-winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure., (© 2021. The Author(s).)

Background: Subarachnoid bleeding is associated with brain injuries and ranges from almost negligible to acute and life threatening. The main objectives were to study changes in brain-specific biomarker levels in patients after an aneurysmal subarachnoid hemorrhage (aSAH) in relation to early clinical findings, severity scores, and intensive care unit (ICU) outcome. Analysis was done to identify specific biomarkers as predictors of a bad outcome in the acute treatment phase., Methods: Analysis was performed for the proteins of neurofilament, neuron-specific enolase (NSE), microtubule-associated protein tau (MAPT), and for the proteins of glial cells, S100B, and glial fibrillary acidic protein (GFAP). Outcomes were assessed at discharge from the ICU and analyzed based on the grade in the Glasgow Outcome Scale (GOS). Patients were classified into two groups: with a good outcome (Group 1: GOS IV-V, n = 24) and with a bad outcome (Group 2: GOS I-III, n = 31). Blood samples were taken upon admission to the ICU and afterward daily for up to 6 days., Results: In Group 1, the level of S100B (1.0, 0.9, 0.7, 2.0, 1.0, 0.3 ng/mL) and NSE (1.5, 2.0, 1.6, 1.2, 16.6, 2.2 ng/mL) was significantly lower than in Group 2 (S100B: 4.7, 4.8, 4.4, 4.5, 6.6, 6.8 ng/mL; NSE: 4.0, 4.1, 4.3, 3.8, 4.4, 2.5 1.1 ng/mL) on day 1-6, respectively. MAPT was significantly lower only on the first and second day (83.2 ± 25.1, 132.7 ± 88.1 pg/mL in Group 1 vs. 625.0 ± 250.7, 616.4 ± 391.6 pg/mL in Group 2). GFAP was elevated in both groups from day 1 to 6. In the ROC analysis, S100B showed the highest ability to predict bad ICU outcome of the four biomarkers measured on admission [area under the curve (AUC) 0.81; 95% CI 0.67-0.94, p < 0.001]. NSE and MAPT also had significant predictive value (AUC 0.71; 95% CI 0.54-0.87, p = 0.01; AUC 0.74; 95% CI 0.55-0.92, p = 0.01, respectively). A strong negative correlation between the GOS and S100B and the GOS and NSE was recorded on days 1-5, and between the GOS and MAPT on day 1., Conclusion: Our findings provide evidence that brain biomarkers such as S100B, NSE, GFAP, and MAPT increase significantly in patients following aSAH. There is a direct relationship between the neurological outcome in the acute treatment phase and the levels of S100B, NSE, and MAPT. The detection of brain-specific biomarkers in conjunction with clinical data may constitute a valuable diagnostic and prognostic tool in the early phase of aSAH treatment.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

Blood coagulation disorders in patients with intracranial bleeding as a result of head injuries or ruptured aneurysms are a diagnostic and therapeutic problem and appropriate assessments are needed to limit CNS damage and to implement preventive measures. The aim of the study was to monitor changes in platelet aggregation and to assess the importance of platelet dysfunction for predicting survival. Platelet receptor function analysis was performed using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating protein (TRAP), ristocetin (RISTO) upon admission to the ICU and on days 2, 3, and 5. On admission, the ASPI, ADP, COL, TRAP, and RISTO tests indicated there was reduced platelet aggregation, despite there being a normal platelet count. In 'Non-survivors', the platelet response to all agonists was suppressed throughout the study period, while in 'Survivors' it improved. Measuring platelet function in ICU patients with intracranial bleeding is a strong predictor related to outcome: patients with impaired platelet aggregation had a lower 28-day survival rate compared to patients with normal platelet aggregation (log-rank test p = 0.014). The results indicated that measuring platelet aggregation can be helpful in the early detection, diagnosis, and treatment of bleeding disorders.

Background: Identifying patients at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) remains challenging. This study aimed to evaluate the concentration of serum biomarkers along with cerebral autoregulation impairment on DCI., Methods: 55 patients suffering from aSAH were enrolled in the study. Serum S100protein B (S100B) was tested both on the day of admission and over three consecutive days following the occurrence of aSAH. Cerebral autoregulation was assessed using a tissue oxygenation index (TOxa) based on near-infrared spectroscopy., Results: Changes in serum S100B levels interacted with DCI status (presence vs. absence): F = 3.84, p = 0.016. Patients with DCI had higher S100B concentration level on day 3 than those without DCI (3.54 ± 0.50 ng/ml vs. 0.58 ± 0.43 ng/ml, p = 0.001). S100B concentration on day 3 following aSAH predicted DCI (AUC = 0.77, p = 0.006). Raised level of serum S100B on day 3 was related with higher TOxa, thus with impaired cerebral autoregulation (r S  = 0.52,p = 0.031). Multivariate logistic regression analysis showed thatimpaired cerebral autoregulation andelevatedS100B concentration on day 3 increasethe likelihood of DCI., Conclusions: Tracking changes in the serum biomarkers concentration along with monitoring of cerebral autoregulation, may play a role in early detection of patients at risk of DCI after aSAH. These results need to be validated in larger prospective cohorts., Competing Interests: Conflict of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported., Approach and Results: The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p < 0.001). Endotoxin had no significant effect on changes in the response of the receptor after ristocetin stimulation. After stopping endotoxin infusion, a significant restoration of receptor activity was observed for collagen and TRAP, while ASPI and ADP remained partially depressed. Inhaled nitric oxide did not cause additional inhibition of platelet aggregation, either during or after endotoxin challenge., Conclusions: A profound reduction in platelet aggregation was observed during endotoxic shock. After stopping endotoxin infusion a restoration of platelet receptor activity was seen. The inhibition of platelet aggregation induced by endotoxin infusion was not intensified by nitric oxide, indicating there was no harmful effect of inhaled nitric oxide on platelet aggregation., (Copyright © 2020. Published by Elsevier Inc.)

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality predictors after aSAH. In patients with an external ventricular drain, enolase, S100B, and GFAP levels were measured in the blood and cerebrospinal fluid (CSF) on days 1, 2, and 3 after aSAH. Compared to survivors, non-survivors showed a significantly higher peak of S100B and enolase levels in the blood (S100B: 5.7 vs. 1.5 ng/mL, p = 0.031; enolase: 6.1 vs. 1.4 ng/mL, p = 0.011) and the CSF (S100B: 18.3 vs. 0.9 ng/mL, p = 0.042; enolase: 109.2 vs. 6.1 ng/mL, p = 0.015). Enolase showed the highest level of predictability at 1.8 ng/mL in the blood (AUC of 0.873) and 80.0 ng/mL in the CSF (AUC of 0.889). The predictive ability of S100B was also very good with a threshold of 5.7 ng/mL in the blood (AUC 0.825) and 4.5 ng/mL in the CSF (AUC 0.810). In conclusion, enolase and S100B, but not GFAP, might be suitable as biomarkers for the early prediction of in-hospital mortality after aSAH.

Introduction: There are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock., Aim: To assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment., Material and Methods: We enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 × 75 mg; ticagrelor, 2 × 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists., Results: Response to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one., Conclusions: Some patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia Sp. z o. o.)

One of the most common complications after cardiac surgery with cardiopulmonary bypass (CBP) is delirium. The purpose of this study was to prospectively investigate the risk of developing postoperative delirium in a group of elderly patients using a multivariate assessment of preoperative and intraoperative risk factors. A total of 149 elderly patients were included. Thirty patients (20%) developed post-operative delirium. Preoperative procalcitonin (PCT) above the reference range (>0.05 ng/mL) was recorded more often in patients who postoperatively developed delirium than in the non-delirium group (50% vs. 27%, p = 0.019). After surgery, PCT was significantly higher in the delirium than the non-delirium group: ICU admission after surgery: 0.08 ng/mL vs. 0.05 ng/mL p = 0.011), and for consecutive days (day 1: 0.59 ng/mL vs. 0.25 ng/mL, p = 0.003; day 2: 1.21 ng/mL vs. 0.36 ng/mL, p = 0.006; day 3: 0.76 ng/mL vs. 0.34 ng/mL, p = 0.001). Patients with delirium were older (74 vs. 69 years, p = 0.038), more often had impaired daily functioning (47% vs. 28%, p = 0.041), depressive symptoms (40% vs. 17%, p = 0.005), and anemia (43% vs. 19%, p = 0.006). In a multivariable logistic regression model, preoperative procalcitonin (odds ratio (OR) = 3.05), depressive symptoms (OR = 5.02), age (OR = 1.14), impaired daily functioning (OR = 0.76) along with CPB time (OR = 1.04) were significant predictors of postoperative delirium.