The role of Toll-like receptor 4 gene polymorphism in the development of organ dysfunction in patients with severe pneumonia associated with A/H1N1 influenza

The aim of the study. To identify the frequency of occurrence of TLR4 Asp299Gly (rs4986790) gene polymorphism and to establish its contribution to the development of organ dysfunction in patients with severe pneumonia associated with A/H1N1 influenza.Materials and methods. The study included 55 patients with severe pneumonia associated with A/H1N1 influenza. Inclusion criteria: severe pneumonia; consolidation/ground-glass syndrome according to chest X-ray/CT. Exclusion criteria: unstable hemodynamics; body mass index > 30; diabetes mellitus; HIV; tuberculosis, oncopathology. Verification of the pathogen in the respiratory swab was carried out using PCR method: A/H1N1  influenza virus RNA was identified. The age of  the  patients was 47 [38; 62] years. Among all the patients the proportion of men was 47.8 %, of women – 52.2 %. Patients were divided into 2 groups: group 1 included patients with SOFA scale (Sequential Organ Failure Assessment) score ≥ 2 points; group 2 – patients with SOFA scale score ˂ 2 points. Gene SNPs were determined by PCR method using standard kits developed by Research and Production Company “Litekh” (Moscow). Amplification of the TLR4 gene fragments was carried out in a thermocycler Bis-M111 (Bis-N LLC, Novosibirsk). Genomic DNA isolated from whole blood leukocytes using the “DNA Express Blood” reagent was analyzed followed by an amplification reaction. The amplification product was detected in a 3% agarose gel.Results. Multiple organ dysfunction (SOFA scale score ≥ 2 points) in patients with severe pneumonia associated with A/H1N1 influenza was registered in 24 (43.6 %) cases. When analyzing the frequency of occurrence of the minor Gly allele, according to genetic models, the differences were established between patients of the groups 1 and 2 in codominant (p = 0.023; odds ratio (OR) – 8.82 (0.95–81.89)) and dominant (p = 0.005; OR = 12.35 (1.40–109.07)) models.Conclusion. Severe pneumonia associated with A/H1N1 influenza is accompanied by a high incidence of  organ dysfunction. The risk of organ failure development is  2.1  times increased in patients with severe pneumonia with identified TLR4 Asp299Gly gene polymorphism, which probably requires further study

Role of proteins MRP8 (S100A8) and MRP14 (S100A9) in the development of critical condition in patients with pneumonia with A/H1N1 influenza

Background. Today, the critical care medicine is actively developing, and rapid progress is closely related to the achievements of molecular biology, immunology, and pathological physiology. The study of the role of individual molecular structures in the realization of the reactions of innate and adaptive immunity, which underlie the pathogenesis of critical conditions, is an urgent scientific direction and is of interest.Aims. To assess the contribution of the protein complex MRP-8/14 to thedevelopment of systemic inflammation by determining its plasma  concentration in patients with pneumonia with influenza A/H1N1.Materials and methods. 85 patients with pneumonia associated with influenza A/H1N1 were examined. Of these, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The plasma concentration of the S100A8/A9 protein complex (MRP-8/14) was determined by flow cytometry on an analyzer (Beckman Coulter, USA).Results. It was found that in patients with severe pneumonia with influenza A/H1N1, the concentration of MRP-8/14 increased in 1.9 times compared  with healthy. At the same time, in patients with severe pneumonia with influenza A/H1N1 with a fatal outcome, the concentration of MRP-8/14 increased in 2.1 times.Conclusion. An increase in the level of MRP-8/14 in patients with severe pneumonia associated with influenza A/H1N1, on the one hand, reflects the severity of the course of systemic inflammation, on the other hand, the molecules MRP-8 and MRP-14, acting as damage-associated molecular patterns (DAMPs) stimulate a pro-inflammatory response and contribute to the development of critical state. Thereby, the protein complex MRP-8/14 can be considered as a potential point of application of pharmacological action in the intensive care of critical conditions

Acute kidney injury in patients with pneumonia with A/H1N1 influenza

Background. A critical condition of any genesis may be accompanied by the development of multiple organ failure, one of the manifestations of which is acute renal injury. Often, the process is subclinical in nature and the «classical» approaches to diagnose renal damage by creatinine concentration, urea level and assessment of glomerular filtration rate may not fully reflect the degree of impaired renal function, while acute kidney injury is a well-known predictor of high hospital mortality among critically ill patients.Aims. The purpose of this study was to assess functional state of the kidneysby determining the serum concentration of the markers of kidney injury  NGAL and Cystatin C in patients with pneumonia associated with influenza A/H1N1.Materials and methods. 85 patients with pneumonia associated with influenza A/H1N1 were examined, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The control group was formed by 15 healthy donors. The serum concentration of NGAL and Cystatin C molecules was determined by flow cytometry on a Beckman Coulter analyzer (USA), using a Human Immune Checkpoint Panel 1 multiplex assay kit (Biolegend, USA). The glomerular filtration rate was calculated using the CKD-EPI formula.Results. It was found that in patients with severe pneumonia with the influenza A/H1N1, the concentration of NGAL increased 3.8 times compared with the control group, the concentration of Cystatin C increased 1.4 times, the glomerular filtration rate did not change.Conclusion. Timely diagnosis of subclinical kidney injury makes it possible to  objectify the severity of the condition, make adjustments to therapy, which can help to an increase in the survival rate of critically ill patients

Активность системы негативной регуляции Т-клеточного ответа PD-1/PD-L1/PD-L2 у больных пневмониями на фоне гриппа A/H1N1

Systemic inflammation is an integral pathophysiological component of many critical illnesses. The systemic inflammatory response is based on a cascade of interactions leading to hypercytokinemia and, as a consequence, multiple organ failure, which is one of the main causes of mortality in intensive care units.Aim of the study. To evaluate the activity of the negative regulation system of T-cell response by determining the plasma levels of PD-1, PD-L1 and PD-L2 molecules in pneumonia patients with influenza A (H1N1).Materials and methods. 85 patients with pneumonia and underlying influenza A (H1N1) were examined. Among them there were 30 patients with severe pneumonia, and 55 patients with non-severe pneumonia. Plasma levels of PD-1, PD-L1, PD-L2 molecules was determined by flow cytofluorometry method.Results. In patients with severe pneumonia and underlying influenza A (H1N1), the plasma level of PD-1 receptor increased 4.6-fold, while the concentration of its ligands PD-L1 and PD-L2 increased 10.6 and 2.2-fold, respectively.Conclusion. Significant increase in levels of PD-1 and its ligands PD-L1 and PD-L2 in patients with pneumonia and underlying influenza A (H1N1) indicates the involvement of negative regulation system of T-cell response in the cascade of immunological reactions and is associated with the severe disease. Possible correction of immune reactions realized through PD-1/PD-L1/PD-L2 complex in critically ill patients is a promising research avenue.Системное воспаление является неотъемлемой патофизиологической составляющей многих критических состояний. В основе системного воспалительного ответа лежит каскад взаимодействий, приводящий к гиперцитокинемии, и, как следствие, к полиорганной недостаточности, которая является одной из основных причин летальности в отделениях интенсивной терапии.Цель работы. Оценить активность системы негативной регуляции Т-клеточного ответа, определив плазменную концентрацию молекул PD-1, PD-L1 и PD-L2 у больных пневмониями на фоне гриппа A/H1N1.Материалы и методы. Обследовали 85 больных пневмонией на фоне гриппа A/H1N1. Из них 30 пациентов с тяжелой пневмонией, 55 — с нетяжелой пневмонией. Методом проточной цитофлуометрии определяли плазменную концентрацию молекул PD-1, PD-L1, PD-L2.Результаты. Установили, что у больных тяжелой пневмонией на фоне гриппа A/H1N1 плазменная концентрация рецептора PD-1 повышалась в 4,6 раза, при этом концентрация его лигандов PD-L1 и PD-L2 увеличивалась в 10,6 и в 2,2 раза, соответственно.Заключение. Статистически значимое увеличение концентрации PD-1 и его лигандов PD-L1 и PD-L2 у больных пневмонией на фоне гриппа A/H1N1 свидетельствует о вовлечении в каскад иммунологических реакций системы негативной регуляции Т-клеточного ответа и ассоциировано с тяжестью состояния. Возможная коррекция иммунных реакций, реализуемых через комплекс PD-1/PD-L1/PD-L2 у пациентов в критическом состоянии — это перспективное научное направление

Организация медицинской помощи больным с тяжелыми пневмониями на фоне гриппа А/H1N1

The paper describes the way medical and intensive cares are organized to patients with complicated forms of A/H1N1 and seasonal influenzas in the Trans-Baikal Territory in the fall of 2009.В статье приведены особенности организации медицинской помощи и интенсивной терапии больным с осложненными формами гриппа A/H1N1/09 и сезонного гриппа в Забайкальском крае осенью 2009 года

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

Background Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates