Effect of Convalescent Plasma Therapy on Mortality and Viral Load in Severely Ill Patients with COVID-19.

The use of convalescent plasma (CP) appeared to be a promising, easily available and safe way of treatment of severe COVID-19 at the onset of the pandemic in early 2020. Conducted in 2020 and 2021, our study of 52 severely to critically ill COVID-19 patients who received CP plasma as a treatment and of 97 controls found no difference in 30-day or 90-day mortality rates. A significant viral load drop in most patients (4.7 log10 [p<0.001] copies/ml) was observed following CP administration. Retrospective analysis of selected inflammatory markers and immunoglobulins showed higher C-reactive protein levels among the study group, and their decrease on Day 7.

Bacteremia in Patients with Sepsis in the ICU: Does It Make a Difference?

Sepsis (and septic shock) is on of the most common causes of death worldwide. Bacteremia often, but not necessarily, occurs in septic patients, but the impact of true bacteremia on a patient's clinical characteristics and outcome remains unclear. The main aim of this study was to compare the characteristics and outcome of a well-defined cohort of 258 septic patients with and without bacteremia treated in the intensive care unit (ICU) of a tertiary center hospital in Prague, Czech Republic. As expected, more frequently, bacteremia was present in patients without previous antibiotic treatment. A higher proportion of bacteremia was observed in patients with infective endocarditis as well as catheter-related and soft tissue infections in contrast to respiratory sepsis. Multivariant analysis showed increased severity of clinical status and higher Charlson comorbidity index (CCI) as variables with significant influence on mortality. Bacteremia appears to be associated with higher mortality rates and length of ICU stay in comparison with nonbacteremic counterparts, but this difference did not reach statistical significance. The presence of bacteremia, apart from previous antibiotic treatment, may be related to the site of infection.

Myristic Acid Serum Levels and Their Significance for Diagnosis of Systemic Inflammatory Response, Sepsis, and Bacteraemia.

Myristic acid is identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Its significant decrease has been observed in patients with septic shock not responding to treatment. Another study has reported a close correlation of myristic acid levels with the outcome of severe trauma patients. Myristic acid concentrations were investigated in a cohort of septic patients and patients with Systemic Inflammatory Response Syndrome (SIRS) in 5 consecutive days following diagnosis and compared to healthy controls. The study population groups-Sepsis 34, SIRS 31, and Healthy Control 120 patients were included. Serum samples were analyzed using gas chromatography and mass spectrometry. The myristic acid levels in the Sepsis Group and SIRS Group were found to be significantly higher when compared to healthy controls. The serum concentration of myristic acid in septic patients with bacteraemia was higher than in septic patients without bacteraemia. Most patients with sepsis and SIRS had the highest levels of myristic acid within 24 h after an established diagnosis. Myristic acid should be considered as a new candidate marker of severe inflammation and sepsis. A simplified analysis and sufficient body of validated data are necessary steps towards the introduction of this metabolite into routine clinical practice.

Kinetics of Myristic Acid Following Accidentally Induced Septic Response.

Myristic acid was identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Subsequently, its significant decrease was observed in patients in septic shock not responding to treatment. In our study we have captured myristic acid serum level kinetics in 96 hours following accidental intravenous self-administration of eubiotic Hylak forte causing infection-like systemic inflammatory response syndrome (SIRS). To our knowledge, this is the first time the kinetics of myristic acid levels is presented in a septic patient. Myristic acid was evaluated in comparison with other inflammatory biomarkers and with its level in a control group of healthy subjects. Myristic acid levels during septic response were significantly elevated in comparison with the control group. The peak level was recorded almost immediately after the insult with a gradual decrease within 96 hours. Myristic acid appears to be a promising biomarker in sepsis diagnostics, further research by our group into this topic is ongoing.

Sepsis Diagnostics in the Era of "Omics" Technologies.

Sepsis is a multifactorial clinical syndrome with an extremely dynamic clinical course and with high diverse clinical phenotype. Early diagnosis is crucial for the final clinical outcome. Previous studies have not identified a biomarker for the diagnosis of sepsis which would have sufficient sensitivity and specificity. Identification of the infectious agents or the use of molecular biology, next gene sequencing, has not brought significant benefit for the patient in terms of early diagnosis. Therefore, we are currently searching for biomarkers, through "omics" technologies with sufficient diagnostic specificity and sensitivity, able to predict the clinical course of the disease and the patient response to therapy. Current progress in the use of systems biology technologies brings us hope that by using big data from clinical trials such biomarkers will be found.

Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment?

Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the early identification of septic patients and their treatment. These improvements in support and therapy mean that mortality is gradually decreasing, however, the rate of death from sepsis remains unacceptably high. Immunotherapy is not currently part of the routine treatment of sepsis. Despite experimental successes, the administration of agents to block the effect of sepsis mediators failed to show evidence for improved outcome in a multitude of clinical trials. The following survey summarizes the current knowledge and results of clinical trials on the immunotherapy of sepsis and describes the limitations of our knowledge of the pathogenesis of sepsis. Administration of immunomodulatory drugs should be linked to the current immune status assessed by both clinical and molecular patterns. Thus, a careful daily review of the patient's immune status needs to be introduced into routine clinical practice giving the opportunity for effective and tailored use of immunomodulatory therapy.

Epidemiology of hospital-acquired pneumonia: Results of a Central European multicenter, prospective, observational study compared with data from the European region.

BACKGROUND: Hospital-acquired pneumonia (HAP) is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of HAP. This project was aimed at collecting multicenter epidemiological data on patients with HAP in the Czech Republic and comparing them with supraregional data. METHODS: This prospective, multicenter, observational study processed data from a database supported by a Czech Ministry of Health grant project. Included were all consecutive patients aged 18 and over who were admitted to participating intensive care units (ICUs) between 1 May 2013 and 31 December 2014 and met the inclusion criterion of having HAP. The primary endpoint was to analyze the relationships between 30-day mortality (during the stay in or after discharge from ICUs) and the microbiological etiological agent and adequacy of initial empirical antibiotic therapy in HAP patients. RESULTS: The group dataset contained data on 330 enrolled patients. The final validated dataset involved 214 patients, 168 males (78.5%) and 46 females (21.5%), from whom 278 valid lower airway samples were obtained. The mean patient age was 59.9 years. The mean APACHE II score at admission was 21. Community-acquired pneumonia was identified in 13 patients and HAP in 201 patients, of whom 26 (12.1%) had early-onset and 175 (81.8%) had late-onset HAP. Twenty-two bacterial species were identified as etiologic agents but only six of them exceeded a frequency of detection of 5% (Klebsiella pneumoniae 20.4%, Pseudomonas aeruginosa 20.0%, Escherichia coli 10.8%, Enterobacter spp. 8.1%, Staphylococcus aureus 6.2% and Burkholderia cepacia complex 5.8%). Patients infected with Staphylococcus aureus had significantly higher rates of early-onset HAP than those with other etiologic agents. The overall 30-day mortality rate for HAP was 29.9%, with 19.2% mortality for early-onset HAP and 31.4% mortality for late-onset HAP. Patients with late-onset HAP receiving adequate initial empirical antibiotic therapy had statistically significantly lower 30-day mortality than those receiving inadequate initial antibiotic therapy (23.8% vs 42.9%). Patients with ventilator-associated pneumonia (VAP) had significantly higher mortality than those who developed HAP with no association with mechanical ventilation (34.6% vs 12.7%). Patients having VAP treated with adequate initial antibiotic therapy had lower 30-day mortality than those receiving inadequate therapy (27.2% vs 44.8%). CONCLUSIONS: The present study was the first to collect multicenter data on the epidemiology of HAP in the Central European Region, with respect to the incidence of etiologic agents causing HAP. It was concerned with relationships between 30-day patient mortality and the type of HAP, etiologic agent and adequacy of initial empirical antibiotic therapy.

Sepsis biomarkers.

Sepsis is the most frequent cause of death in non-coronary intensive care units (ICUs). In the past 10 years, progress has been made in the early identification of septic patients and in their treatment and these improvements in support and therapy mean that the mortality is gradually decreasing but it still remains unacceptably high. Leaving clinical diagnosis aside, the laboratory diagnostics represent a complex range of investigations that can place significant demands on the system given the speed of response required. There are hundreds of biomarkers which could be potentially used for diagnosis and prognosis in septic patients. The main attributes of successful markers would be high sensitivity, specificity, possibility of bed-side monitoring, and financial accessibility. Only a fraction is used in routine clinical practice because many lack sufficient sensitivity or specificity. The following review gives a short overview of the current epidemiology of sepsis, its pathogenesis and state-of-the-art knowledge on the use of specific biochemical, hematological and immunological parameters in its diagnostics. Prospective approaches towards discovery of new diagnostic biomarkers have been shortly mentioned.

Spontaneous breathing of heliox using a semi-closed circuit: a bench study.

INTRODUCTION: The use of helium-oxygen mixture (heliox) for ventilation has an advantage in patients with obstruction of the airways. The physical properties of helium enable an easier gas flow through the airways; this enables easier breathing for the patient when compared to standard ventilation of air. A high cost of heliox falls within the factors that limit the use of heliox in clinical practice. At present, heliox is administered by use of an open circuit. The aim of this study is to propose a way of heliox administration that reduces heliox consumption but does not affect the positive heliox effects upon the airway resistance. METHODS: To minimize consumption of heliox, a semi-closed circuit has been designed. The circuit is a modification of an anesthetic circuit composed of parts with the lowest possible resistances. As any circuit has its own resistance, the evaluation of its possible negative effect upon the work of breathing of patients with exacerbation of chronic obstructive pulmonary disease (COPD) has been conducted. RESULTS: A semi-closed circuit for heliox administration has been constructed and evaluated. The intrinsic resistance of both the inspiratory and expiratory limbs of the circuit is less than 140 Pa.s/l. This resistance does not represent a significant workload for a patient with COPD exacerbation whose airway resistance is 10 to 20 fold higher. CONCLUSIONS: The designed semi-closed circuit offers a potential benefit of heliox in patients with COPD exacerbation.

Induction of procalcitonin in liver transplant patients treated with anti-thymocyte globulin.

INTRODUCTION: The aim of this study was to compare the early postoperative kinetics of procalcitonin (PCT) and C-reactive protein (CRP) serum levels in patients undergoing orthotopic liver transplantation (OLTx) with different immunosuppressive regimens. METHODS: PCT and CRP serum concentrations were measured in a group of 28 OLTx recipients before induction of anesthesia, at 4 and 8 hours following graft reperfusion, and daily until postoperative day 4. The same parameters were determined in 12 patients undergoing liver resection without conjunctive immunosuppressive therapy. Summary data are expressed as medians and ranges. Two-tailed nonparametric tests were performed and considered significant at p values of less than 0.05. RESULTS: The highest serum levels of PCT (median 3.0 ng/mL, minimum 1.4 ng/mL, maximum 13.9 ng/mL) were found in patients after OLTx without ATG therapy, on postoperative day 1. In patients with ATG administration, PCT levels were highly increased on postoperative day 1 (median 53.0 ng/mL, minimum 7.9 ng/mL, maximum 249.1 ng/mL). Thereafter, PCT values continuously decreased independently of further ATG administration in both groups of patients. No evidence of infection was present in either group. In 12 patients undergoing liver resection, peak serum PCT levels did not exceed 3.6 ng/mL. CRP serum levels in a group of patients with and without ATG therapy increased significantly on postoperative day 1, followed by a decrease. The highest levels of CRP were found in patients after liver resection on postoperative day 2 and decreased thereafter. CONCLUSION: ATG administration to patients with OLTx is associated with an increase in serum PCT levels, with peak values on postoperative day 1, and this was in the absence of any evidence of infection. The results of this study indicate that ATG immunosuppressive therapy is a stimulus for the synthesis of PCT.

Expression profiling: toward an application in sepsis diagnostics.

Sepsis is a common and serious health problem whereby improvements in diagnosis are crucial in increasing survival rates. To test whether profiling transcription is applicable to sepsis diagnosis, we analyzed whole blood using a microarray containing probes for 340 genes relevant to inflammation. The patient's gene expression pattern was highly homogenous, resulting in 69% of differentially expressed genes. With a positive predictive value of 98%, a list of 50 differentially expressed genes was compiled, and randomly chosen transcripts were confirmed by PCR. Here, we present the first evidence that microarrays can identify typical gene expression profiles in the blood of patients with severe sepsis. Regardless of the heterogeneity of the patients, we observed a striking correlation between the conventional diagnostic classification and our approach. The unity of responses suggests that the principle of this multiparameter approach can be adapted to early stage sepsis diagnosis.

Significance of lipopolysaccharide-binding protein (an acute phase protein) in monitoring critically ill patients.

INTRODUCTION: The present study was conducted to assess the value of serum concentration of lipopolysaccharide-binding protein (LBP) in patients with systemic inflammatory response syndrome (SIRS), sepsis and septic shock with respect to its ability to differentiate between infectious and noninfectious etiologies in SIRS and to predict prognosis. METHODS: This prospective cohort study was conducted in a multidisciplinary intensive care unit. Sixty-eight patients, admitted consecutively to the intensive care unit and who met criteria for SIRS, sepsis or septic shock were included. Serum LBP was measured using an immunochemiluminiscence assay. RESULTS: Serum levels of LBP were significantly increased in patients with SIRS (n = 40; median 30.6 microg/ml, range 9.2-79.5 microg/ml), sepsis (n = 19; median 37.1 microg/ml, range 11.8-76.2 microg/ml) and septic shock (n = 9; median 59.7 microg/ml, range 31.1-105 microg/ml), as compared with levels in the healthy volunteers (5.1 +/- 2.2 microg/ml; P < 0.0001). Serum LBP at study entry was statistically significantly lower in patients with SIRS than in those with septic shock (P < 0.014); no statistically significant difference existed between patients with SIRS and those with sepsis (P = 0.61). Specificity and sensitivity of an LBP concentration of 29.8 microg/ml to distinguish between infectious and noninfectious etiologies for SIRS were 50% and 74.2%, respectively. There was no statistically significant difference in LBP concentration between survivors and nonsurvivors in both groups of patients. Furthermore, in septic patients the LBP response appeared to exhibit a decreased magnitude. CONCLUSION: LBP is a nonspecific marker of the acute phase response and cannot be used as a diagnostic tool for differentiating between infectious and noninfectious etiologies of SIRS.