CLINICAL STUDIES
Objective. To evaluate the relationship between immunological parameters and functional outcome in patients with varying severity of ischemic stroke based on statistical methodology.
Materials and methods. The prospective study included 78 patients diagnosed with ischemic stroke, who were distributed into two groups: group 1 — 38 mild stroke patients, NIHSS score < 5, group 2 — 40 moderate stroke patients, NIHSS score 5–15. Signs of stroke severity, degree of disability, cognitive decline, and activities of daily living were chosen as criteria to estimate the functional outcome by calculating the difference between the NIHSS, mRS, MoCA, and BI scales at the time of admission and on Day 12 of hospital stay. Lab tests included assessment of plasma concentrations of CXC and CC subfamilies of cytokines, interleukins and TNF-a on Day 2 of hospital stay. Machine learning algorithms, the Python programming language, the Pandas and SciPy libraries, and discriminant analysis were used for statistical processing.
Results. The following parameters were found as significant: concentrations of IL-1b and MPIF-1/CCL23 for — for group 1, and concentrations of IL-16, MPIF-1/CCL23, Eotaxin-2/CCL24, Gro-a/CXCL1 and IL-8/CXCL8 for group 2 patients. Positive correlation was established between NIHSS dynamics and concentrations of TNF-a (R=0.227, P=0.001), MPIF-1/CCL23 (R=0.380, P=0.00061) and Gro-a/CXCL1 (R=0.211, P=0.00001), and between changes in mRS and concentrations of MPIF-1/CCL23 (R=0.277, P=0.00006), Gro-a/CXCL1 (R=0.211, P=0.0075) and IL-16 (R=0, 211, P=0.00001). There was a significant negative correlation between cognitive dysfunction and concentrations of Eotaxin-2/CCL24 (R=–0.378, P=0.00075), Gro-a/CXCL1 (R=–0.313, P=0.0035), and IP-10/CXCL1 (R=–0.214, P=0.00023), and between limited activities of daily living (IB) and concentrations of MPIF-1/CCL23 (R=–0.345, P=0.0024) and Gro-a/CXCL1 (R=–0.210, P=0.00001).
Conclusion. Chemokines form the CC family — MPIF-1/CCL23 and Eotaxin-2/CCL24, and the CXC-Gro-a/CXCL1 and IL-16 clusters are the principal cytokines associated with the dynamics of patient’s motor and cognitive functions recovery in the acute period of ischemic stroke. Although obtained results demonstrate negative effect of increased MPIF-1/CCL23, Gro-a/CXCL1, IL-16 and Eotaxin-2/CCL24 concentrations on the improvement of motor and cognitive impairments, further studies are needed to verify the CXC and CC subfamilies chemokines as prognostic markers of patient’s functional outcome in the acute period of ischemic stroke.
Objective. To study the morphometric characteristics and splenic immune cell response in patients with COVID-19.
Material and methods. A prospective observational study included 70 patients. Of these, 45 patients admitted to the infectious diseases hospital with Coronavirus infection caused by the SARS-CoV-2 virus diagnosis were included in the COVID-19 group, and 25 patients were included in the acute respiratory viral infection (ARVI) comparison group. Spleen linear dimensions, including length, width, and thickness were assessed using ultrasound imaging, and calculations of the spleen weight and spleen weight coefficient (SWC) were obtained. Additionally leukocyte count and formula, erythrocyte sedimentation rate (ESR) were estimated, and the leukocyte index (LI) and neutrophil-to-lymphocyte ratio (NLR) were calculated.
Results. Microsplenia was common in the acute period of COVID-19 with mean SWC value 1.6±0.2. In 17 (37.8%) patients the SWC varied from 1.0 to 1.5, and in 9 (20%) microsplenia was critical with SWC <1.0. Leukocyte count was lower, and ESR — higher in patients with COVID-19, compared to ARVI group (5.4±2.1×10⁹/l and 10.8±4.8×109/l, respectively P<0.00001, and ESR — 36.1±13.8 mm/h and 23.0±5.1 mm/h, respectively P=0.03). The course of COVID-19 was characterized by a slight decrease in LI — from 0.29±0.02 to 0.22±0.01 (P=0.19), and significant increase in NLR from 3.7±0.1 to 4.3±0.12 (P=0.002). Opposite trends were documented in patients with ARVI. On Day 5 since initiation of treatment LI was significantly lower in the COVID-19 vs ARVI group (0.22 [0.16; 0.39] vs. 0.48 [0.29; 0.93], P=0.003), and NLR was significantly higher (4.3 [2.5; 6.1] vs. 2.1 [0.9; 2.9], P=0.002).
Conclusion. The course of coronavirus infection caused by the SARS-CoV-2 virus is characterized by significant immunological shifts. Microsplenia verified by ultrasonography stays as one of the pathognomonic signs. This phenomenon is explained by rapid «depletion» of the spleen as a secondary immune organ, and is associated with a high risk of developing acute immune deficiency.
FOR PRACTIONER
Objective. A comparative assessment of the efficacy and safety of the preemptive use of ibuprofen and ketoprofen in patients undergoing elective surgery under general anesthesia.
Material and methods. A multicenter randomized prospective study included 58 patients grouped into 2 arms. Ibuprofen 800 mg in Group 1 (N=32), and ketoprofen 100 mg in Group 2 (N=26) were administered intravenously 30 minutes prior to surgical procedure, and afterwards every 12 hours during patient’s stay in the intensive care unit. Efficacy and safety were assessed using a visual analog scale (VAS), patient’s need in opioid analgesics, laboratory parameters (serum levels of cortisol, cystatin C, CBC, coagulogram, TEG) and instrumental methods (algesimetry — qNOX).
Results. VAS values were 32.4% lower in Group 1 vs Group 2 in the immediate postoperative period, P=0.003. By the end of Day 1 this difference was no longer visible following the use of promedol. There was a correlation between qNOX values at the end of surgery and VAS values at patient’s waking up from anesthesia (P=0.0007). Cortisol plasma concentrations in groups 1 and 2 did not differ significantly, P=0.105. The average daily promedol consumption in Groups 1 and 2 was 42±17.5 mg/day and 50±19.7 mg/day, respectively, P=0.022. Cystatin C concentrations in the first morning after surgery was 0.95±0.29 mg/l in the ibuprofen group, and 1.19±0.43 mg/l — in the ketoprofen group, P=0.027. Signs of renal dysfunction were documented in 4 out of 32 patients (12, 5%) from Group 1, and in 10 of 26 (38.5%) patients from Group 2 since the end of surgery and up to the first postop morning, the Chi-squared value was 0.031. Hemostasis was not affected by NSAIDs use in both groups.
Conclusion. Ibuprofen provided more powerful analgesia, than ketoprofen in the postoperative period, while during surgical procedure both drugs showed similar anlgesic efficacy. Patients on ibuprofen required significantly fewer additional boluses of opioid analgesics. Both drugs showed no clinically significant effect on hemostasis and hematopoiesis. More rare occurrence of renal dysfunction in Group 1 patients is indicative of lower nephrotoxicity of ibuprofen.
Aim of the study was to determine the advantages of peripheral nerve blocks (PNB) versus local infiltration anesthesia (LIA) in the formation of arteriovenous fistula (AVF) surgically created for hemodialysis treatment
Type of study: prospective non-randomized study. Approved by the ethics committee of JLF UK in Martin.
Type of workplace: clinical workplace of a university hospital.
Material and method. The cohort of patients (N=40) who required arteriovenous fistula (AVF) creation was divided into 2 groups, 20 patients each: patients operated under peripheral nerve blockade and patients operated under local infiltration anesthesia. The preserved function of the fistula was monitored 24 hours, 6 weeks and one year after the operation, without revision. Patient inclusion criteria included: age 19–75 years, ASA 3–4, weight 40–120 kg, BMI up to 40. Statistical treatment of data included Mann-Whitney exact test, Fisher's test, t-test, Shapiro–Wilk normality test.
Results. After 24 hours, all fistulas created with peripheral nerve blockade were functional whereas only 90% developed under local infiltration anesthesia remained functional (P>0.05 between groups). However, after 6 weeks, 80% of fistulas created under peripheral nerve block were functional, compared to 50% of functional fistulas created in patients under local infiltration anesthesia (P=0.048). One year after surgery, the difference remained as a trend since 55% of fistulas created under peripheral nerve block remained functional while only 35% of fistulas created in patients receiving local infiltration anesthesia were functional without complications (P=0.097).
Conclusion. In our study, the peripheral nerve block anestesia seem superior in term of improved survival of created fistula compared to local infiltration anesthesia.
EXPERIMENTAL STUDIES
Up to 57% of patients develop postoperative delirium after surgery for congenital heart defects (CHD). To reduce cerebral damage in pediatric patients during CHD surgery it is important to find out what inflicts the worse damage: would it be a systemic inflammatory response (SIR) triggered by transfusion, or hypoxia developed in non-transfused patients? In vitro evaluation of hypoxia and SIR effects on the neurovascular unit (NVU) cells might contribute to finding the answer.
The aim of the study was to compare the effect of varying severity hypoxia and SIR on the functional activity of NUV cells in vitro.
Materials and methods. An in vitro NVU model was designed including neurons, astrocytes and endotheliocytes. The effect of hypoxia on NVU was evaluated in the control (C) and 4 study groups (H 1–4), formed based on O₂ content in the medium. The C group NVU were cultivated in standard conditions: N₂ — 75%, O₂ — 20%, CO₂ — 5%; H1: N₂ — 99%, O₂ — 1%; H2: N₂ — 98%, O₂ — 2%; H3: N₂ — 97%, O₂ — 3%; H4: N₂ — 96%, O₂ — 4%. The significance of the differences was 0.0125. The effect of interleukin-6 (IL-6) content on NVU was measured by adding to culture medium pediatric patients’ serum with known minimal or maximal SIRS-response. The assessment was made in the Control — an intact NVU model, and 2 study groups — «Minimum» and «Maximum», i. e. samples with minimum or maximum IL-6 content in culture, respectively. The significance of the differences was 0.017. The cells were incubated at a normothermia regimen for 30 minutes. Then, the functional activity of NVU cells was evaluated by measuring transendothelial resistance (TER) for 24 hours and Lucifer Yellow (LY) permeability test at 60 and 90 minutes after the start of the experiment.
Results. After incubation under hypoxic conditions, TER changes occurred in all studied groups. However, they were statistically significant only in the group with 1% oxygen content in the medium. TER decrease in this group was observed after 2, 4 and 24 hours. LY permeability also changed at 60 and 90 minutes, similarly — in NVU cultivated with 1% oxygen in the medium. Minimal TER values were documented at 4 hours after patients’ serum was added to NVU cells culture medium, and TER increased at 24 hours in both study groups. Cellular permeability to LY changed significantly after 1 hour exposure in both groups — with minimum and maximum IL-6 content in the medium. Although at 90 minutes, there was no difference between the 3 groups in LY permeability tests.
Conclusion. Intensive SIR demonstrated short-term but more deleterious than hypoxia, effect on cells in the NVU model. Hypoxia disrupted functional activity of NUV cells only at 1% O₂ concentration in the medium.
Pericarditis is a group of polyetiological diseases often associated with emergence of life–threatening conditions. Poor knowledge of underlying cellular mechanisms and lack of relevant approaches to investigation of pericarditis result in major challenges in diagnosis and treatment.
The aim of this work was to identify changes in the activity of autophagy in epicardial cells in acute pericarditis.
Materials and methods. Acute pericarditis in mice was induced by intrapericardial injection of Freund's adjuvant in the study group (n=15). The control group included animals receiving either intrapericardial injection of phosphate-buffered saline (PBS) (n=15), or sham surgery without injections (n=7). On Days 3 or 5 after surgery the animals were euthanized under isoflurane anesthesia. Immunofluorescence staining of cardiac tissue cryo-sections and immunoblotting were used to assess the intensity of inflammation and autophagy in the epicardium.
Results. Inflammation and other signs of acute pericarditis resulting in thickening of some epicardial areas were found: 68+9% in the control (after PBS injection) and 124+22% after Freund's adjuvant injection (p=0.009); other signs included cellular infiltration of epicardium and multiple adhesions. The epicardial layer exhibited signs of mesothelial cells reorganization with 11-fold increase of autophagy markers LC3 II/LC3 I ratio: 0.07+0.02 in the control group (after PBS injection) and 0.84+0.07 - in acute pericarditis (p=0.04), and accumulation of collagen fibers.
Conclusion. Development of acute pericarditis is accompanied by activation of epicardial mesothelial cells, intensified autophagy and development of fibrous changes in epicacardial/ subepicardial areas.
The aim of the study. To study the effect of high nitric oxide concentrations on hollow polypropylene fibers of oxygenators.
Materials and methods. The study was conducted in two stages. At the first stage, we evaluated the stability of oxygenator membrane made of hollow polypropylene fibers after six hours of exposure to air-oxygen mixture containing NO at 500 parts per million, or 500 pro pro mille (ppm) concentration, using mass spectrometry and infrared spectroscopy. At the second stage, an experiment with cardiopulmonary bypass (CPB) was conducted on 10 pigs. In the study group (n=5) animals sweep gas was supplied to the oxygenator as an air-oxygen mixture with NO at 100 ppm. In the control group animals (n=5) an air-oxygen mixture was used without NO. The CPB lasted for 4 hours, followed by observation for 12 hours. NO, NO2 (at the inlet and outlet of the oxygenator), and the dynamics of methemoglobin were evaluated. After weaning of animals from CPB, the oxygenators were tested for leakproofness, and scanning electron microscopy (SEM) was performed.
Results. The oxygenator made of polypropylene hollow fibers retained its gas transfer parameters after six hours of exposure to air-oxygen mixture containing NO at 500 ppm. Based on IR-Fourier spectroscopy findings, NO did not affect structural integrity of polypropylene membranes. NO added to gas mixture at 100 ppm did not increase NO2 to toxic level of 2 ppm in 91% of control tests during 4 hours CPB in pigs; mean value was 1.58 ± 0.28 ppm. Methemoglobin concentration did not exceed the upper limit of permissible level (3%), and there were no statistically significant differences with the control group. All tested oxygenators have passed the leakproofness test. According to SEM findings, larger amounts of fibrin deposits were found in the control group oxygenators vs study group.
Conclusion. There were no negative effects of NO at 500 ppm concentration on the oxygenator membrane made of hollow polypropylene fibers. NO at 100 ppm in a gas-mixture supplied to oxygenators did not lead to an exceedance of safe NO2 and methemoglobin concentrations in an animal model. Reduced fibrin deposits on hollow fibers of polypropylene oxygenator membranes were observed when with NO at a level of 100 ppm was added to a gas mixture.
META-ANALYSIS
Metastatic processes remain the main cause of deaths in oncology. Methods of anesthesia, in particular regional anesthesia, are considered as potential modulators of the immune response and metastatic spread. The ambiguity of the available data on the effect of regional and general anesthesia on metastatic spread is partly due to the fact that general anesthetic in combined anesthesia is quite often not taken into account, and this, in turn, masks the possible influence of regional anesthesia.
The purpose of this meta-analysis was to make a comparative assessment of the effect of general anesthesia and general anesthesia in combination with regional anesthesia on the relapse-free and overall survival of cancer patients after surgery.
Materials and methods. We analyzed 8 randomized controlled trials involving 1822 patients and comparing the groups of cancer patients who were operated either under general anesthesia (total intravenous (TIVA) or inhalation (IA)), or general anesthesia in combination with regional anesthesia (TIVA+RA or IA+RA, respectively). Trial using combinations of inhaled and intravenous anesthetics was excluded from the analysis for a more accurate assessment of the effect of regional anesthesia. The study complies with the recommendations of the Cochrane Community and PRISMA standards. The protocol was registered on the INPLASY platform. We used PubMed, Google Scholar and CENTRAL databases. We used a subgroup analysis and GRADE tool to assess the quality of evidence.
Results. There were no statistically significant differences in relapse-free and overall survival when comparing different anesthesia methods. For a relapse-free survival, comparing TIVA vs TIVA+RA resulted in no significant difference : OR=1.20 [95% CI 0.92-1.55]; when IA vs IA+RA were compared, OR=1.10 [95% CI 0.94-1.29]. Similar results were obtained for overall survival.
Conclusion. Based on the meta-analysis results, regional anesthesia had no effect on relapse-free and overall survival in oncosurgery patients.
ISSN 2411-7110 (Online)