Platelet dysfunction in a large-animal model of endotoxic shock; effects of inhaled nitric oxide and low-dose steroid.

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.

Influenza in patients with respiratory failure admitted to intensive care units in Poland and the use of extracorporeal respiratory support: a survey-based multicenter study.

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 (ECCO2R) 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.

Biomarkers of Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage as Early Predictors at Discharge from an Intensive Care Unit.

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.

Plasma and Cellular Forms of Fibronectin as Prognostic Markers in Sepsis.

BACKGROUND: There is a pressing need for specific prognostic markers that could be used to monitor the severity of sepsis. The aims of our study were to investigate changes in the expression of different molecular forms of fibronectin in sepsis and to assess their relationship to the clinical severity and mortality of patients. Material and Methods. Forms of fibronectin: plasma (pFN), cellular (EDA-FN), FN-fibrin complexes, and fibronectin fragments were analyzed in 71 sepsis patients (survivors and nonsurvivors) and in the control by ELISA and immunoblotting. RESULTS: The baseline pFN concentration of patients with sepsis was significantly lower than in the control (133.0 mg/L vs. 231.2 mg/L) (P < 0.001), and in nonsurvivors, it was lower than in survivors (106.0 mg/L vs. 152.8 mg/L) (P = 0.004). The baseline EDA-FN was significantly elevated in both sepsis groups (survivors: 6.7 mg/L; nonsurvivors: 9.4 mg/L) compared to the control (1.4 mg/L) (P < 0.001). It should be noted that among patients with more severe sepsis, the EDA-FN level was higher in nonsurvivors than in survivors. Furthermore, molecular FN-fibrin complexes as well as FN fragments occurred much more frequently in nonsurvivors than in survivors. CONCLUSION: The study showed that in sepsis, changes in plasmatic and cellular form of fibronectin were associated with the severity of sepsis and may be useful predictors of outcome.

Interleukin-18 serum levels in sepsis: Correlation with disease severity and inflammatory markers.

PURPOSE: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and a syndrome shaped by pathogen and host factors with characteristic that evolve over time. The study was conducted to evaluate the prognostic and discriminative value of IL-18 assessment in comparison to PCT, CRP, WBC in early stage of sepsis and septic shock. METHODS: An observational and prospective study was conducted in the group of 40 ICU patients with diagnosis of sepsis or septic shock, serum PCT, IL-18, CRP and WBC measurements were performed on admission, and on the 2nd, 3rd and 5th therapy day. The level of IL-18 was determined with commercially available test according to manufacturer's protocol. RESULTS: There were no statistically significant differences in IL-18 levels in survivors vs non-survivors and in sepsis vs septic shock subgroups the IL-18 levels were statistically significant in the course of the study except for the 5th day. CONCLUSION: The PCT, CRP and WBC levels revealed no significant differences between any analyzed subgroups in all time points during study. According to our results the IL-18 is a biomarker better differentiating sepsis and septic shock status than PCT, CRP and WBC but with no prognostic impact.

Prolonged Cardiopulmonary Bypass is a Risk Factor for Intestinal Ischaemic Damage and Endotoxaemia.

BACKGROUND: Intestinal ischaemia-reperfusion, a frequent occurrence during cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. We hypothesised that ischaemia-reperfusion following prolonged CPB could increase intestinal permeability and thus, lead to endotoxin translocation from the intestine to the bloodstream. MATERIAL AND METHODS: Patients subjected to coronary artery bypass grafting with CPB were included: Group 1 (CPB ≥90minutes) or Group 2 (CPB <90minutes). Intestinal Fatty Acid Binding Protein (I-FABP), TNF alpha, IL6, IL8, and endotoxin levels were measured before the induction of general anaesthesia (T1), at 6 (T2), and 24hours (T3) after surgery. RESULTS: The low level of I-FABP at T1 increased for every patient in Group 1 at T2 (from 1015.5pg/mL to 2608.5pg/mL, p=0.02) and in Group 2 (from 1123.5pg/ml to 2284.0pg/ml, p<0.001). Furthermore, at T3, the I-FABP level was over three times higher in Group 1 than in Group 2 (2178pg/mL vs 615pg/mL; p<0.001). I-FABP correlated with CPB time (R=0.6, p<0.001) at T3. After surgery, endotoxins were elevated in 73% of patients in Group 1 and in 32% in Group 2 and correlated with CPB time (at T2, R=0.5, p=0.002; at T3, R=0.4, p=0.016). CONCLUSIONS: The duration of CPB is linked to the release of biomarkers that indicate ischaemic-reperfusion damage to the gastrointestinal mucosa and endotoxaemia. I-FABP assay may help to identify patients presenting with intestinal damage, who are at risk of bacterial translocation.

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study.

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.

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.

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.

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.

Mechanical ventilation in ICUs in Poland: a multi-center point-prevalence study.

BACKGROUND: Mechanical ventilation is the primary method of supporting organ function in patients treated in intensive care units (ICUs). Lung damage from mechanical ventilation can be avoided by using the correct ventilation modes. This study was designed to assess the epidemiology and treatment strategies of patients receiving mechanical ventilation in ICUs in Poland. MATERIAL AND METHODS: This study was done using a point-prevalence methodology. Questionnaires requesting demographic data, indications for ventilation, variables involved in ventilation, airway access, methods of sedation, and mode of weaning were sent to 148 ICUs. RESULTS: Eighty-three ICUs took part in the study. The rate of ventilated patients was 73.6%. The indications for mechanical ventilation were: acute respiratory failure (40%), coma (40%), chronic obstructive pulmonary disease (COPD) exacerbation (14%), and neuromuscular diseases (5%). Patients were ventilated by orotracheal tube (58%), tracheostomy tube (41%), and mask/helmet (1%). The mean tidal volume was 8 ml/kg and positive end-expiratory pressure was commonly used. The mean oxygen concentration was 40%. Synchronized intermittent mandatory ventilation with pressure support was the most frequently used ventilatory mode. Benzodiazepine and opioids were used for sedation in 91% of centers. A systematic testing of the depth of sedation was performed at 48% surveyed ICUs. Ventilation monitoring with biomechanical methods was used at 53% of centers. CONCLUSIONS: Mechanical ventilation is commonly used in ICUs in Poland. Almost half of the ventilated patients had extrapulmonary indications. Patients were ventilated with low concentrations of oxygen, and positive end-expiratory pressure (PEEP) was commonly employed.

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.

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.

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.

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.

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.

Dysnatremia in COVID-19 Patients-An Analysis of the COLOS Study.

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.

Association of serum vitamin D concentration with the final course of hospitalization in patients with COVID-19.

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 m2 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.

Assessment of Clinical Indicators Registered on Admission to the Hospital Related to Mortality Risk in Cancer Patients with COVID-19.

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.

Usefulness of the Veterans Health Administration COVID-19 (VACO) Index for Predicting Short-Term Mortality among Patients of the COLOS Study.

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.