REVIEWS & SHORT COMMUNICATIONS
Personalized medicine (PM) is a major trend in health care development in the 21st century. This area includes studying risk factors for disease development (prediction), interventions for preventing diseases (prophylaxis), individualization of diagnosis and treatment (personalization), informing the patient on disease prevention and treatment (participation). In the recent years, an intense research to introduce the personalized medicine principles into the management of critically ill patients, has been under way. This includes identification of patient groups based on genomic research, development of diagnostic tests using molecular markers, creation of novel classes of drugs based on individual patient characteristics.
The aim of the review is to summarize the available data on the implementation of the principles of PM in the routine practice of critical care institutions.
We analyzed more than 300 sources of literature from the Pubmed and Scopus databases, as well as the RSCI database. Eighty five most relevant sources were selected for the review. The paper reports data on the organization and results of implementation of PM principles and advanced technologies, such as Emergency Medicine Sample Bank (EMSB), in the daily activity of clinics providing emergency critical care. The formation of the novel PM concept focused on the treatment of critically ill patients has been discussed. The review contains detailed data on the patterns of development of specific critical illnesses such as acute cerebrovascular events, acute respiratory distress syndrome, traumatic brain injury, shock, myocardial infarction, cardiac rhythm and conduction disturbances. Medication efficacy in view of individual genetic patient characteristics has also been highlighted. No research limitations on the subject were identified.
Conclusion. The analysis of literature has demonstrated positive results of implementing PM principles in prevention, diagnosis and treatment of critically ill patients. Creation of Biobanks, development of training programs and regulatory documentation, advancing the scientific research, introduction of new methods of diagnosis and treatment will contribute to the implementation of PM principles in practical healthcare.
Paroxysmal sympathetic hyperactivity (PSH) is one of the complications of acute severe brain injuries (traumatic brain injury, intracranial hemorrhage, ischemia, and posthypoxic conditions) in both adults and children. Its high incidence and severe sequelae including organ dysfunction, infectious complications, impaired blood supply to organs and tissues associate with increased disability and mortality. The choice of effective therapy can be challenging because of multifaceted manifestations, diagnostic difficulties, and lack of a clear understanding of the pathophysiology of PSH. Currently, there are various local and international treatment strategies for PSH.
The aim of the review is to summarize clinical and scientific research data on diagnosis and treatment of PSH to aid in the selection of an effective therapy.
Material and methods. Web of Science, Scopus and RSCI databases were employed to select 80 sources containing relevant clinical and research data on the subject of this review.
Results. The key principles of diagnosis and treatment of paroxysmal sympathetic hyperactivity have been reviewed. The current views on etiology and pathogenesis of paroxysmal sympathetic hyperactivity development were outlined. The clinical data concerning complications and sequelae of paroxysmal sympathetic hyperactivity were analyzed. We conclude the review with a discussion of current methods of the syndrome prevention.
Conclusion. Preventing PSH and its adequate and prompt treatment could help avoid the abnormal pathway development following a severe brain injury, reduce its negative consequences and rate of complications, along with the duration of mechanical lung ventilation, patient's stay in ICU, disability and mortality rates. Careful selection of pathogenetic, symptomatic and supportive therapy significantly improves the rehabilitation potential of patients.
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FOR PRACTIONER
Introduction and aim. Recent evidence suggests that inhalation anesthesia (IA) is associated with higher cancer mortality than total intravenous anesthesia (TIVA), possibly due to a modulation of the immune response.
The aim of this study was to determine the impact of anesthesia techniques on selected parameters of patient immunity considering the evidence of relationship between the anesthesia methods and immune status and, consequently, the incidence of cancer recurrence.
Methods. We performed a meta-analysis of clinical studies published in PubMed, Google Scholar, and Cochrane databases, aimed at assessing the impact of anesthesia on the postoperative immune status of patients undergoing breast cancer (BC) surgery. Five randomized and three observational studies were included (a total of 637 patients, of which 320 (50.2%) in the TIVA group). Data on leukocyte counts, matrix metalloproteinases (MMP) 9 and 3, interleukins (IL) 6 and 10 levels, and neutrophil-lymphocyte index (NLI) values were retrieved.
Results. Patients after breast cancer surgery who underwent TIVA had significantly lower white blood cell counts (standardized mean difference (SMD)=–0.32; 95% CI: –0.58 to –0.06; I2=58%, P=0.020) and MMP-9 (SMD=–0.35; 95% CI: –0.67 to –0.03; P=0.030; I2=0%) in the postoperative period compared with patients receiving IA. No significant differences in the levels of MMP-3, IL-6, IL-10, and NLI values were found between the two groups.
Conclusion. The patients who underwent breast cancer surgery under TIVA had lower blood leukocyte counts and levels of MMP-9, which is involved in the remodeling of extracellular matrix, compared with those operated on under IA, suggesting that the anesthesia method may have an impact on the immunity of breast cancer patients.
The aim of the study was to evaluate the role of urapidil hydrochloride for the management of abnormal cardiovascular response in patients undergoing robot-assisted radical prostatectomy (RARP).
Material and methods. The total of 93 prostate cancer patients scheduled for elective RARP were included and randomized in two groups: urapidil (n=44) and standard anesthesia control group (n=49). Urapidil was used to control the elevated blood pressure intraoperatively. Central hemodynamic monitoring was performed at 5 steps of the surgery.
Results. In the control group, the step 2 of the procedure was associated with elevated mean blood pressure (by 24.3%, P=0.045) and increased total peripheral vascular resistance (by 46.6%, P=0.011) compared with step 1, while in the urapidil group no significant changes in these parameters were found. In the urapidil group, the blood pressure was lower by 20.2% (P=0.047), afterload by 36.9% (P=0.02) vs the control group values, whereas the cardiac output was higher by 22.2% (P=0.043). Placing patient in the steep Trendelenburg position (step 3) resulted in a 22.4% increase in stroke volume (P=0.38) in the control group and a 19.2% increase in stroke volume (P=0.049) in the urapidil group compared with the previous step. Cardiac output in the urapidil group was higher by 34% (P=0.002) and blood pressure and vascular resistance were lower by 24.4% (P=0.031) and 45.7% (P=0.001), respectively, vs the control group. At steps 4 and 5, gradual stabilization of the hemodynamic parameters and peripheral vascular tone with significantly smaller differences between the groups were revealed.
Conclusion. Urapidil was effective for maintaining central hemodynamic parameters in patients during robotic-assisted radical prostatectomy at step 2 of the procedure, avoiding blood pressure elevation at step 3 and significantly reducing the total peripheral vascular resistance compared with the control group.
EXPERIMENTAL STUDIES
Mitochondrially targeted antioxidants based on Skulachev ions (SkQ1) are extremely attractive for neutralizing reactive oxygen species directly in the mitochondrial matrix.
The aim was to examine the antioxidant and cardioprotective status of the SkQ1 mitochondrially targeted antioxidant in an isolated rat heart model of ischemia and reperfusion after cold cardioplegia.
Material and methods. The effects of different concentrations of SkQ1 (1200 ng/ml, 120 ng/ml, 12 ng/ml) were explored on isolated hearts of Wistar rats (n=50) during 240-min cold cardioplegia. The levels of oxidative stress, changes in myocardial damage markers (classical and highly specific) and cardiac function (coronary flow velocity, heart rate, systolic pressure) were assessed.
Results. The use of SkQ1 at 12 ng/ml resulted in a significant neutralization of oxidative stress manifestations (P<0.05). The minimum concentration of NO metabolites (nitrates and nitrites) (36.2 [30.8; 39.8] µmol/ml) was maintained at pre-ischemic level throughout the 30-minute reperfusion period, while the malonic dialdehyde concentration (49.5 [41.1; 58.9] µmol/g) was lower compared with SkQ1 use at 120 ng/ml dose. Due to the «mitigation» of oxidative stress, intracellular enzymes and highly specific markers of myocardial damage rose more slowly during reperfusion, while cardiac function recovery occurred at a higher rate and showed stability upon restoration of perfusion.
Conclusion. SkQ1 at 12 ng/ml concentration showed strong antioxidant and cardioprotective properties in an ex vivo study.
CLINICAL STUDIES
The aim of the study was to identify the risk factors of spontaneous pneumomediastinum and to determine its management strategy in patients with the novel coronavirus infection.
Material and methods. Eighteen patients with spontaneous pneumomediastinum (SPM) hospitalized in the Center for Novel Coronavirus Infection of the Mechnikov Northwestern State Medical University from 2020 to 2021 were examined. The control group consisted of 18 persons selected using matched sampling. We analyzed symptoms, medical and life history, comorbidities, physical examination results, laboratory and instrumental data, and disease management of patients in both groups
Results. The groups were comparable by age and sex. Among all patients hospitalized with the novel coronavirus infection, spontaneous pneumomediastinum was registered in 1.3% (n=18). Analysis of symptoms, medical and life history, comorbidities, physical examination results, laboratory and instrumental data and disease management did not reveal significant differences between the groups. At the same time, the proportion of obese patients in the main group was lower than in the control group. Estimation of HR showed that the risk of spontaneous pneumomediastinum development was significantly lower in obesity (HR=0.14; 95% CI: 0.033–0.63, P=0.010).
Conclusion. The risk of spontaneous pneumomediastinum is significantly lower in obese patients.
One of the main problems facing intensivists when treating patients with COVID-19 is severe and critical acute respiratory distress syndrome (ARDS) with the underlying viral pneumonia. The current guidelines of the Russian Ministry of Health (Version 15 of 22.02.22) do not include drugs with a lung protective effect. This issue could be solved by administration of a synthetic analogue of leu-enkephalin.
Aim. Study the efficacy of a synthetic analogue of leu-enkephalin in ARDS in patients with COVID-19.
Materials and methods. The study included 35 patients divided into 2 groups. Group 1 (main) patients (n=15) in addition to standard therapy received a continuous infusion of synthetic analogue of leu-enkephalin at a rate of 5 µg/kg/hour for 5 days. Patients from group 2 (control, n=20) were treated according to the Temporary Guidelines of the Ministry of Health (V.15), but without the synthetic analogue of leu-enkephalin. The radiological data, frequency, severity and evolution of respiratory complications, changes in P/F (PaO2/FiO2) ratio, as well as changes in the scores of prognostic APACHE II, SOFA, and NEWS scales were evaluated.
Results. In patients taking the studied drug, the percentage of lung damage did not change with the median (IQR) of 0 [–8; 0], while in the control group it increased by approximately 10% with the median (IQR) of +10,0 [+2; +20] (P=0.001). The proportion of patients in group 1 with positive disease evolution within 5–9 days after treatment initiation was significantly higher and reached 46.7 [24.8; 69.9]%, whereas in group 2 it was 15.0 [5.2; 36.0]% (P=0.04). Also, in group 1, starting from day 4, the median P/F ratio was significantly higher than in group 2 reaching 220 [185;245] versus 127 [111;158], respectively (P=0.014). The need for non-invasive lung ventilation in group 1 on day 7 averaged 7%, while in group 2 it was as high as 45.0%, which was significantly higher than in the main group (P=0.013).
Conclusions. The use of synthetic analogue of leu-enkephalin according to the specified regimen had a significant impact on the main parameters of the viral pneumonia severity. The results serve as a rationale for the development of a novel effective treatment strategy to supplement the current standard COVID-19 management.
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