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Objective: To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters. Design: Prospective study. Patients: Eighty-three male and 11... more
Objective: To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters. Design: Prospective study. Patients: Eighty-three male and 11 female multiple trauma patients. Measurements: Upon admission, severity of trauma was assessed with the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (SOFA) score and the Injury Severity Score (IS). Concurrently, blood was drawn to measure thyrotropin (TSH), free thyroxine (fT4), trioodothyronine (T3), corticotropin (ACTH), prolactin (PRL), cortisol and dehydroepiandrosterone sulphate (DHEAS). Adrenal reserve was assessed with the Synacthen test. Results: Seventy-five of the 83 men and 8 of the 11 women survived. APACHE II and SOFA scores were higher in non-survivors compared to survivors (with considerable overlap). From the baseline endocrine work-up, survivors had higher ACTH and DHEAS values compared to non-survivors (also with considerable overlap). No differences between survivors and non-survivors were noted in the Synacthen test or in thyroid function tests. Nevertheless, a multivariate logistic regression model that incorporated the APACHE II score and hormonal parameters (Cortisol post-Synacthen, DHEAS, TSH*age) was well-fitted to assess survival/non-survival as an endpoint and better than APACHE II, SOFA or IS scores alone to predict ICU survival or death. Conclusion: In critically ill multiple trauma patients, age, TSH, Cortisol post-Synacthen and DHEAS values upon admission to the ICU, combined with the APACHE II score, may predict outcome more accurately than the APACHE II score alone.an the APACHe II score alone.
The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as... more
The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 +/- 18 years; EF, 63% +/- 7%). The systolic (S) and early diastolic (E') velocity of the mitral annulus by TDI and the E/E' as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (P(O2)/Fi(O2)), sepsis, and ICU mortality were assessed. Systolic, E', and E/E' correlated with age, P(O2)/Fi(O2), lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E' (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.
Introduction: The aim of this study was to compare the differences between elderly and non-elderly patients with AECOPD due to a viral infection. Methods: Patients presenting with an AECOPD were recruited. They were classified as elderly... more
Introduction: The aim of this study was to compare the differences between elderly and non-elderly patients with AECOPD due to a viral infection. Methods: Patients presenting with an AECOPD were recruited. They were classified as elderly (>65 years) and non-elderly ( Results: During the study period 247 patients were recruited [median age 69.3±9.5 years] and categorized in two groups: group A, non elderly [n=81 (32.8%) median age 58±5.99)] and group B elderly patients [n=166 (67.2%) median age 74.8±4.8 years]. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from sputum or blood culture. In 18 (7.3%) patients a dual infection from both a bacterial and a viral pathogen was identified. In Group B influenza vaccination (57% vs 21%, p Conclusion: In this study in elderly patients with AECOPD were identified a higher vaccination rate against influenza, more comorbitities, more bacterial infections and longer hospitalization c...
Patient: Male, 73-year-old Final Diagnosis: Severe COVID-19 pneumonia complicated by right atrium thrombus Symptoms: Fever • dyspnea • cough Medication:— Clinical Procedure: — Specialty: Critical Care Medicine Objective: Educational... more
Patient: Male, 73-year-old Final Diagnosis: Severe COVID-19 pneumonia complicated by right atrium thrombus Symptoms: Fever • dyspnea • cough Medication:— Clinical Procedure: — Specialty: Critical Care Medicine Objective: Educational purpose Background: Recent studies demonstrated evidence of coagulation dysfunction in hospitalized patients with severe coronavirus disease 2019 (COVID-19) due to excessive inflammation, hypoxia, platelet activation, endothelial dysfunction, and stasis. Effective anticoagulation therapy may play a dominant role in the management of severe COVID-19 cases. Case Report: A 73-year-old man with a 6-day history of fever up to 38.5°C, dyspnea, cough, and fatigue was diagnosed with COVID-19. He had a past medical history significant for hypertension and coronary artery bypass grafting. Two days after hospital admission, the patient developed acute respiratory failure, requiring intubation, mechanical ventilation, and transfer to the intensive care unit (ICU). He received treatment including antibiotics, hydroxychloroquine, tocilizumab, vasopressors, prone positioning, and anticoagulation with enoxaparin at a prophylactic dose. After a 15-day ICU stay, the patient was hemodynamically stable but still hypoxemic; a transthoracic echocardiogram at that time, followed by a transesophageal echocardiogram for better evaluation, revealed the presence of a right atrium thrombus without signs of acute right ventricular dilatation and impaired systolic function. Since the patient was hemodynamically stable, we decided to treat him with conventional anticoagulation under close monitoring for signs of hemodynamic deterioration; thus, the prophylactic dose of enoxaparin was replaced by therapeutic dosing, which was a key component of the patient’s successful outcome. Over the next few days he showed significant clinical improvement. The follow-up transesophageal echo-cardiogram 3 weeks after effective therapeutic anticoagulation revealed no signs of right heart thrombus. Conclusions: The presented COVID-19 case, one of the first reported cases with evidence of right heart thrombus by transesophageal echocardiography, highlights the central role of diagnostic imaging strategies and the importance of adequate anticoagulation therapy in the management of severe COVID-19 cases in the ICU.
The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute... more
The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU. On admission, 56% of the patients had increased levels (>200 μmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r=0.260; P=.01), and norepinephrine's dose (r=0.230; P=.01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7±276.0 μmol/L vs 252.2±158.4 μmol/L; P=.03). Subcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.
Background and Aim: Feeding interruptions in critical care patients are often unjustified. We aimed to determine the causes, duration, and frequency of enteral nutrition interruptions (ENIs) and to assess macronutrients and antioxidant... more
Background and Aim: Feeding interruptions in critical care patients are often unjustified. We aimed to determine the causes, duration, and frequency of enteral nutrition interruptions (ENIs) and to assess macronutrients and antioxidant deficits according to European Society of Parenteral Enteral Nutrition (ESPEN) guidelines. Methods: We prospectively enrolled Intensive Care Unit (ICU) patients admitted for more than 48 h with an inability to orally eat from April to December 2019. The type of enteral nutrition, the number of calories administered, the time of feeding initiation, the reasons for delaying feeding, and the causes for ENI were recorded. Results: 81 patients were enrolled, with a median duration of ENIs of 5.2 (3.4–7.4) hours/day. Gastric residual volume (GRV) monitoring—a highly controversial practice—was the most common cause of ENI (median duration 3 (2.3–3) hours/day). The mean energy intake was 1037 ± 281 kcal/day, while 60.5% of patients covered less than 65% of th...
Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation... more
Acute respiratory distress syndrome (ARDS) is defined as a syndrome of acute onset, with bilateral opacities on chest imaging and respiratory failure not caused by cardiac failure, leading to mild, moderate, or severe oxygenation impairment. The syndrome is most commonly a manifestation of sepsis-induced organ dysfunction, characterized by disruption of endothelial barrier integrity and diffuse lung damage. Imbalance between coagulation and inflammation is a predominant characteristic of ARDS, leading to extreme inflammatory response and diffuse fibrin deposition in vascular capillary bed and alveoli. Activated platelets, neutrophils, endothelial cells, neutrophil extracellular traps, microparticles, and coagulation proteases, participate in the complex process of immunothrombosis, which is a key event in ARDS pathophysiology. The present review is focused on the elucidation of immunothrombosis in ARDS and the potential therapeutic implications.
To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters. Prospective study. Eighty-three male and 11 female multiple trauma patients.... more
To evaluate whether tentative prognostic models for intensive care unit survival of multiple trauma patients could be improved by including endocrine parameters. Prospective study. Eighty-three male and 11 female multiple trauma patients. Upon admission, severity of trauma was assessed with the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment (SOFA) score and the Injury Severity Score (IS). Concurrently, blood was drawn to measure thyrotropin (TSH), free thyroxine (fT4), trioodothyronine (T3), corticotropin (ACTH), prolactin (PRL), cortisol and dehydroepiandrosterone sulphate (DHEAS). Adrenal reserve was assessed with the Synacthen test. Seventy-five of the 83 men and 8 of the 11 women survived. APACHE II and SOFA scores were higher in non-survivors compared to survivors (with considerable overlap). From the baseline endocrine work-up, survivors had higher ACTH and DHEAS values compared to non-survivors (also with considerable ov...
Controversial findings of former clinical trials on the effect of low dose hydrocortisone in patients with septic shock led to investigate the effect of corticosteroids on the production of cytokines from endotoxin (LPS)-stimulated whole... more
Controversial findings of former clinical trials on the effect of low dose hydrocortisone in patients with septic shock led to investigate the effect of corticosteroids on the production of cytokines from endotoxin (LPS)-stimulated whole blood. Whole blood from 33 septic patients was sampled within 24h alter diagnosis. Hydrocortisone was not administered during follow-up. Whole blood was stimulated with 30 ng/ml of LPS in the presence of 0.01, 0.1, 1 and 10 microM of dexamethasone. Concentrations of cytokines and of sTREM-1 were estimated in supernatants after six hours of incubation. Dexamethasone inhibited LPS-stimulated release of TauNuFalpha, of IL-6, of IL-8 and of IL-10 in dose-dependent manner. A dual effect on the kinetics of release of IL-1beta and of sTREM-1 was shown. Release of IL-1beta was either decreased, what was connected with unfavorable outcome, or it was unaffected what was connected with a favorable outcome. Release of sTREM-1 was either increased, what was connected with unfavorable outcome, or it was decreased what was connected with a favorable outcome. Part of the beneficiary effect of corticosteroids in sepsis may be due to an effect on the release of IL-1beta and of sTREM-1. This effect does not seem to be homogeneous for all septic patients.
Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients... more
Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L,...
Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular... more
Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ven...
Background: Pulmonary arterial hypertension (PAH) is a disease characterized by vasoconstriction, remodeling and thrombotic pulmonary vascular lesions. Although alterations in hemostasis are consistently observed in PAH patients, their... more
Background: Pulmonary arterial hypertension (PAH) is a disease characterized by vasoconstriction, remodeling and thrombotic pulmonary vascular lesions. Although alterations in hemostasis are consistently observed in PAH patients, their extent and their role in the progression of the disease remain largely unclear. Aims: The aim of this study is to evaluate primary platelet- related hemostasis, using point- of care methods, like the Platelet- Function Analyzer (PFA-100) and Light Transmission Aggregometry (LTA). Methods: The study group consisted of 21 patients with PAH, diagnosed according to current ESC/ERS guidelines. Blood samples were obtained directly from the pulmonary artery. The PFA-100 testing was performed using collagen epinephrine (CEPI) - coated cartridges. Platelet activation in LTA was induced by ADP and epinephrine. Results: 53,4% of the patients presented prolonged CEPI closure times with PFA-100 testing [median (IQR), 161 (122–192)]. ADP- induced platelet aggregation was reduced [60 (45–70)] in 33,3% of the patients and disaggregation (not normally seen in healthy individuals) was present in another 57,14%. In addition, 53,4% of the population presented reduced EPI- induced aggregation. No significant correlation was found between the degree of platelet dysfunction and the mean pulmonary arterial pressure [mean 47.6 ± 12.9 mmHg] or the pulmonary vascular resistance [9.3±4.2 Wood Units]. Conclusions: These preliminary data provide evidence of significant impaired primary hemostasis and severe platelet dysfunction demonstrated in the vast majority (90%) of PAH patients.
ABSTRACT Computer assistance for medical decision-making has been of growing interest since the 1950s. Hemodynamic diagnosis is based on the multiparametric integration of several numeric data that may be easily computerized. The goal of... more
ABSTRACT Computer assistance for medical decision-making has been of growing interest since the 1950s. Hemodynamic diagnosis is based on the multiparametric integration of several numeric data that may be easily computerized. The goal of this study was to develop a diagnostic tool that is easy to use and available at the bedside. To achieve this goal, it was necessary to systematize each step of the hemodynamic diagnosis before programming a pocket computer. We first selected hemodynamic data necessary for diagnosis. We created theoretic values of hemodynamic variables for each individual patient according to age, sex, temperature, and metabolic status. Afterward, we compared theoretic and observed values using an algorithmic procedure, which led us to define several diagnostic words. We evaluated our system by comparing the diagnostic performance of the pocket computer with that of three physicians in the assessment of 214 hemodynamic profiles recorded in four intensive care units. The computer diagnosis was good in more than 90% of the cases, and acceptable in 99% of the cases for one physician. The chance-corrected Kappa coefficient showed a poor initial agreement when diagnoses were independently made by the computer and the physician, but there was a significant overall improvement when the physician made use of the computer in a reevaluation. In an instance of discordance between a physician and the computer, a neutral physician significantly agreed with the computer. We conclude that the use of a pocket computer for hemodynamic evaluation is convenient and reliable.
Hashish smoke has been proved to be active in the Sidman avoidance. Its activity is similar to that of hallucinogens.
Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of... more
Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the ...
Ventilator-associated tracheobronchitis (VAT) is an infection commonly affecting mechanically ventilated intubated patients. Several studies suggest that VAT is associated with increased duration of mechanical ventilation (MV) and length... more
Ventilator-associated tracheobronchitis (VAT) is an infection commonly affecting mechanically ventilated intubated patients. Several studies suggest that VAT is associated with increased duration of mechanical ventilation (MV) and length of intensive care unit (ICU) stay, and a presumptive increase in healthcare costs. Uncertainties remain, however, regarding the cost/benefit balance of VAT treatment. The aim of this narrative review is to discuss the two fundamental and inter-related dilemmas regarding VAT, i.e., (i) how to diagnose VAT? and (ii) should we treat VAT? If yes, should we treat all cases or only selected ones? How should we treat in terms of antibiotic choice, route, treatment duration?
On 18 August 2019, an article was published in Microorganisms presenting novel, approved anti-Gram-positive antibiotics. On 19 August 2019, the U.S. Food and Drug Administration announced the approval of lefamulin, a representative of a... more
On 18 August 2019, an article was published in Microorganisms presenting novel, approved anti-Gram-positive antibiotics. On 19 August 2019, the U.S. Food and Drug Administration announced the approval of lefamulin, a representative of a new class of antibiotics, the pleuromutilins, for the treatment of adult community-acquired bacterial pneumonia. We present a brief description of lefamulin.
Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was... more
Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-i...
Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this... more
Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propag...

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