In Russia and European countries, the incidence of pressure (decubitus) ulcers in sedentary patients with severe comorbidities, spinal trauma, and cerebral accident sequelae varies from 3 to 40 %, reaching 80 % in the chronic critical illness. The final result of conservative treatment of pressure ulcers (PU) with adequate correction of comorbidities and proper care of the immobilized patient depends largely on the choice of local interventions.

   Aim of the review: to demonstrate the range of effective methods of physical treatment of pressure ulcers suitable for conservative treatment.
   Materials and methods. We selected and analyzed 80 scientific publications. Sources were selected from the PubMed, Scopus, and RSCI databases of medical and biological publications. The following methods were covered: negative pressure wound therapy, ultrasonic methods, hydrosurgical treatment, plasma flows, laser therapy (including low-level laser therapy), «hardware» acceleration of regenerative processes, including electrical stimulation, as well as a combination of these methods.
   Results. The variety of physical methods of wound treatment, on the one hand, provides an opportunity to select an individual therapy program. On the other hand, each method has its own limitations and contraindications. That is why in practice various combinations of these methods are reasonable.
   Conclusion. For several objective reasons, no reduction of PU incidence in clinical practice is expected. Therefore, studying the issues of evidence-based clinical effectiveness and economic feasibility of various conservative techniques of decubitus treatment to find best solutions in this area is warranted.

   Aim: to evaluate clinical effectiveness of selective hypothermia of cerebral cortex for the recovery of awareness in patients with chronic disorders of consciousness (CDC).
   Material and methods. 111 patients with CDC 30 and more days after a cerebral event (ischemic or hemorrhagic stroke, brain injury) were included in the study. Exclusion criteria were anoxic brain injury (sequelae of a prolonged asystole or asphyxia), active sepsis, arrhythmia, baseline hypothermia (body temperature lower than 35.5 °С). Experimental group included 60 patients, of them 39 patients were in a vegetative state (VS), 21 patients exhibited patterns of minimally conscious state (MCS). Control group incluted 51 patients, of them 32 patients were in VS and 19 patients were in MCS. Patients in the experimental group received 10 sessions (120 minutes each) of selective brain hypothermia (SBH) during the 14-days follow-up period. Patients of both groups received standard identical neurological treatment and rehabilitation procedures. Patients in the control group did not undergo brain hypothermia. The induction of SBH involved cooling of the whole surface of the craniocerebral area of scalp using special helmets. The temperature of the internal surface of the helmet was 3–7 °С. Temperature of the frontal lobes of the cortex was monitored with non-invasive microwave radiothermometry, axillary temperature was also registered. The level of consciousness was evaluated using «Coma Recovery Scale-Revised» (CRS-R) scale.
   Results. 120-minutes long SBH session reduced the temperature of the frontal lobes of the cerebral cortex by 2.4–3.1 °С with no impact on the axillary temperature. Evaluation using CRS-R revealed improvement in all studied functions (auditory, visual, motor, oromotor, communication, arousal) in patients in the experimental group after 10 SBH sessions. Level of consciousness in patients from the experimental group in VS increased from 4.5 ± 0.33 to 8.7 ± 0.91 points (P < 0.001), for patients in MCS from 11.3 ± 1.0 to 18.2 ± 0.70 (P < 0.001) points. In the control group, scores of patients in VS rose from 4.3 ± 0.37 to 6.8 ± 0.49 (P < 0.001) points with the most significant changes in auditory and visual functions (P<0.001). In the control group of patients in MCS the oromotor function improved (P < 0.05), overall CRS-R scores changed insignificantly from 9.1 ± 0.57 to 10.1 ± 0.86 (P < 0.1). The best outcome (CRS-R > 19 points) was seen in patients from the experimental group [6 in VS (15.4 %) and 8 in MCS (31.8 %)]. In the control group, the best results did not exceed 10 points for the patents in VS, while 4 patients in MCS (21 %) reached 12–16 scores. During 30-day follow-up period of hospitalization after the SBH sessions mortality rate was 10 % (6 patients) in the experimental group and 21.6% (11 patients) in the control group.
   Conclusion. Patients with CDC could benefit from serial SBH sessions performed as a part of comprehensive treatment and rehabilitation strategy. We suggest that selective reduction of frontal lobe temperature improves neurogenesis, neuronal regeneration, and neuroplasticity.

   Severe traumatic brain injury (TBI) accompanied by impaired consciousness manifesting as prolonged postcoma unawareness (PCU) is one of the current medical and social problems causing high morbidity and mortality worldwide. Difficult recovery of such patients necessitates the development of additional neurorehabilitation approaches, including neuromodulation methods, as well as the search for objective markers of treatment efficacy.
   Aim of the study: to evaluate the effect of therapeutic rhythmic transcranial magnetic stimulation (rTMS) on fMRI resting state networks (RSN) in PCU after severe TBI.
   Materials and Methods. We analyzed individual fMRI RSN in three patients with PCU before and after a course of rTMS performed at different timepoints after severe TBI and with different efficacy of treatment. We assessed the topography and quantitative characteristics of the networks (DMN, sensorimotor, control functions, left and right fronto-parietal, auditory, and speech) known to be most significant for recovery of consciousness.
   Results. We found a trend toward normalization of RSN topography as well as an increase in the integral index of network intensity in two of three patients with a distinct increase in consciousness after a course of rTMS.
   Conclusion. Using case observations, we have demonstrated the therapeutic efficacy of rTMS and feasibility of using fMRI RSN as a reliable diagnostic approach in PCU following severe TBI.

   Identification of complications and control of comorbidities are essential in monitoring the patients with chronic disorders of consciousness and predicting their outcomes. The researchers of the Department of Biotechnological and Applied Clinical Sciences of the University of L'Aquila (Italy) developed the Comorbidities Coma Scale (CoCoS) for a comprehensive assessment of such patients. Lack of an officially validated version of the scale hampers its use in Russia, while using versions which have not been completely validated prevents clinicians from obtaining reliable results when examining patients with chronic disorders of consciousness.
   Aim. To develop the official Russian language version of the Comorbidities Coma Scale, considering various linguistic and cultural parameters, as a part of the 1st stage of the validation study.
   Material and methods. The first stage of validation was completed: direct and reverse translation of the scale was performed by two independent medical translators. The translated version was assessed by an expert board including an expert translator, neurologists, and critical care specialists. Pilot test and two meetings of the expert board, before and after testing, were arranged to assess the results and approve the final Russian version of the scale.
   Results. During the first meeting of the expert board, corrections were made in the Russian language version of the scale in terms of language and cultural adaptation. Pilot testing was carried out based on the inclusion and exclusion criteria. The researchers had no difficulties in understanding and interpreting the instructions for the scale. The second meeting of the expert board was held thereupon, and the final version of the Russian language version of the scale was adopted, which is available on the website of the Center for Validation of Health Status Questionnaires and Scales of the Research Center of Neurology.
   Conclusion. The first stage of validation, i. e., linguistic and cultural adaptation, was carried out at the Research Center of Neurology (Moscow, Russia). For the first time, the Russian version of the scale for assessing comorbidities in patients with chronic disorders of consciousness was presented and approved for the practical use. The future publications will address the psychometric results of the scale such as sensitivity, validity, reliability.

   Aim of the study: to reduce cognitive impairment during laparoscopic cholecystectomy by perioperative administration of drugs with antihypoxic and antioxidant effects under the control of stabilography.
   Materials and methods. We studied the effect of general anesthesia and antioxidants on cognitive, static and locomotor functions during laparoscopic cholecystectomy. We studied 90 patients with acute calculous cholecystitis randomized into three experimental groups (n=30, each group). The control group was composed of 24 healthy individuals. Group 1 patients received no antioxidants, group 2 patients received the combination antioxidant drug (sodium fumarate+sodium chloride+potassium chloride+magnesium chloride) in the post-operative period, and group 3 patients received methylethylpyridinol. The patient groups were comparable in sex, age and type of inflammatory and destructive process in the gallbladder. Surgical intervention was performed under endotracheal anesthesia. Premedication with atropine and promedol was given, and anesthesia induction was carried out with propofol, fentanyl and suxamethonium. Sevoflurane, fentanyl and
cisatracurium were employed to maintain anesthesia, analgesia and myorelaxation, respectively. The patients were examined before surgery, 24 and 48 hours after surgery. In the groups of patients who received antioxidant therapy, blood sampling for hematological and biochemical examinations was performed 30 min after the administration of antioxidants. Stabilographic studies and MoCA test (Montreal Scale) were performed before antioxidant administration prior to surgery and after surgery, on days 2 and 3.
   Results. Neuropsychological testing revealed postoperative cognitive dysfunction on standard therapy which included impaired attention and concentration, executive function, memory, speech, visual constructional skills, abstract thinking, counting, and orientation (21 points on the MoCA scale versus 28–30 points for normal). We found that the pathogenetic factors of cognitive dysfunction included insufficient antioxidant protection, decreased TNF-α and elevated interleukin-18 levels along with an increased level of C-reactive protein in plasma, which manifested as activation of free-radical oxidation processes and reduced antioxidant system and performance of nonspecific resistance. Perioperative use of the combination antioxidant drug and methylethylpyridinol antioxidants reduced the frequency and severity of postoperative cognitive impairment in patients after laparoscopic cholecystectomy.
   Conclusion. The most important pathogenetic factors of cognitive dysfunction after laparoscopic cholecystectomy include activation of free-radical oxidation, reduction of antioxidant defense system performance and lack of nonspecific resistance factors. Adding the combination antioxidant drug or methylethylpyridinol to the standard therapy reduces the intensity of radical oxygen species generation, maintains the antioxidant potential, activates production and secretion of nonspecific resistance factors, preventing the development and reducing the severity of cognitive disorders in the perioperative period. Neuropsychological testing and stabilographic examination allow identifying the risk of cognitive disorders in patients after laparoscopic cholecystectomy and provide a rationale for the use of antioxidant therapy for their prevention.

   Aim of the study: to evaluate the feasibility of preventing cognitive dysfunction after long-term surgery in elderly patients using an original neurometabolic succinate-containing drug.
   Material and methods. A multicenter, double-blind, placebo-controlled randomized trial enrolled 200 patients aged 60–80 years who underwent elective cardiac or orthopedic surgery. The patients received either the study drug (inosine + nicotinamide + riboflavin + succinate) (treatment group, n = 101) or a placebo (control group, n = 99) intravenously for 7 days then orally for 25 days. Efficacy was assessed by the change in the Montreal Cognitive Assessment Scale (MoCA) score at the end of the treatment course compared with the preoperative level.
   Results. Before surgery, the total MoCA score values did not differ between the groups. By the end of the treatment course (31 days after surgery), the MoCA total score was 26.4 ± 1.96 in the main group and 25.0 ± 2.83
in the control group (P < 0.001). The intergroup difference in the mean change in the MoCA total score on day 31 was 1.56 points (95 % CI 1.015; 2.113; P < 0.0001) favoring the study drug in all randomized population. The lower limit of CI (1.015) exceeded the limit of superiority set by the protocol (0.97 points), which allowed acceptance of the hypothesis of superiority of the study drug over placebo with respect to the primary efficacy criterion. No significant differences in the frequency of adverse events were found between the groups.
   Conclusion. The succinate-containing study drug demonstrated an acceptable safety profile and helped to reduce the severity of postoperative cognitive dysfunction in elderly patients who underwent a major surgery, which allows recommending the drug for prevention of postoperative cognitive impairment in high-risk patients.

   The main variants of chronic consciousness disorder (CCD) developing in adverse coma outcome are vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimal consciousness state (MCS).
   The aim of the study was to investigate the main differences in metabolomic abnormalities in patients with VS / UWS and MCS, as well as to identify changes in metabolomics depending on sleep or wakefulness phase.
   Materials and Methods. Untargeted metabolome analysis of blood plasma of 10 patients in VS / UWS (group 1) and 6 patients in MCS (group 2) was performed using reversed-phase and hydrophilic chromatography methods. The underlying conditions of brain injury were TBI (2 in group 1 and 5 in group 2) and hypoxia (8 in group 1 and 1 in group 2). The internal jugular vein was catheterized in all patients, and blood was collected while awake during the daytime for 2 days. Aliquots of pooled plasma samples were purified from protein components and analyzed by high-performance liquid chromatography in two modes: reversed-phase and hydrophilic ones. Mass-spectrometric detection was performed in full ion current scanning mode: registration of positively charged ions in the m/z range from 50 to 1300 a.u. Data were adjusted and normalized using MS-DIAL software ver. 4.70 software; differences were identified using analysis of variance, discriminant and cluster analysis. The data were analyzed and visualized using MetaboAnalyst 5.0 software (https://www.metaboanalyst.ca).
   Results. Four major metabolites (at VIP > 0.5), which content was most modulated depending on the study group, were identified including 4 (m/z 124.0867, Rt = 17.67, p < 0.01), 33 (m/z 782.5722, Rt = 17.69, p < 0.01), 6 (m/z 125.0904, Rt = 18.43, p < 0.01) and 1 (m/z 463.2304, Rt = 15.78, p < 0.01), with no significant differences between daytime and nighttime blood samples. Significant quantitative differences were shown for three metabolites in the groups, 14 (m/z 162.1126, Rt = 10.28, p < 0.01), 35 (m/z 780.5483, Rt = 7.65, p < 0.01), and 41 (m/z 806.5649, Rt = 7.58, p < 0.01), and four metabolites when comparing the daytime and nighttime samples: 14 (m/z 162.1126, Rt = 10.28, p = 0.0201), 35 (m/z 780.5483, Rt = 7.65, p < 0.01), 41 (m/z 806.5649, Rt = 7.58, p < 0.01), and 48 (m/z 848.5354, Rt = 7.65, p < 0.01).
   Conclusion. Untargeted metabolomic analysis confirmed the hypothesis of likely significant quantitative and qualitative differences in metabolite composition depending on the type of CCD and circadian rhythm. The study established a set of metabolites that are potential biomarkers for differential diagnosis of VS/UWS and MCS including 4, 33, 6, 1 (in the experiment on the reversed-phase column) and 14, 35, 41, 48 (in the experiment on the hydrophilic column), based on their significant contribution to intergroup and intragroup differences. Further studies will be aimed to characterize the identified metabolites.

   Aim. To evaluate the efficacy of cascade plasma filtration (CPF) for the correction of lipid profile and biochemical markers (sFlt-1, PIGF, sFlt-1/PIGF) in pregnant women with early preeclampsia.
   Materials and Methods. A prospective controlled study of 23 CPF procedures was conducted in 11 pregnant women with early preeclampsia at gestational ages 22 to 31 weeks. The evolution of clinical manifestations of preeclampsia (BP, urine output, and proteinuria), laboratory biochemical parameters (protein/creatinine ratio, lipid profile), blood coagulation tests, and thromboelastometry (ROTEM) were assessed. In addition, the effect of CPF on the level of preeclampsia markers (sFlt-1, PIGF, sFlt-1/PIGF-ratio) as predictors of endothelial aggression was analyzed. The efficacy of extracorporeal therapy was evaluated based on the duration of pregnancy prolongation.
   Results. The use of CPF as an adjunct for the treatment of early preeclampsia had a positive effect on the lipid profile by reducing cholesterol and LDL, which helped to decrease atherogenic aggression on the vascular endothelium. In addition, the extracorporeal therapy promoted reduction of the anti-angiogenic effect of sFlt-1, which was confirmed by a significant decrease in the sFlt-1/PIGF ratio from 515 [347; 750] to 378 [285; 557] (P = 0.013). The period of prolongation of pregnancy was longer in the main group (with CPF) and was 19 [5; 26] days, whereas in the comparison group (without CPF) it was 3 [1; 4] days (P < 0.001). All newborns were discharged from the hospital in a stable condition. The paper is supplemented with a clinical observation of the effective use of CPF in early preeclampsia.

   Conclusion. The use of cascade plasma filtration in the treatment of early preeclampsia to prolong pregnancy could be a promising approach.

   Neoangiogenesis is the key process determining myocardial regeneration after infarction. The urokinase-type plasminogen activator receptor (uPAR) is known to play an important role in the regulation of endothelial cell function and postnatal angiogenesis. However, uPAR its involvement in the regulation of the properties of vascular progenitor cells remains poorly studied.
   Aim: to evaluate uPAR expression on the surface of resident cardiac vascular progenitor cells (rcVPCs) and its impact on angiogenic cell properties in vitro as well as postinfarction cardiac vascularization.
   Materials and Methods. We used immunofluorescent analysis of cryosections of a murine myocardial infarction model to characterize vessels and rcVPCs, and evaluatedв the angiogenic properties potential of vasculogenic progenitor cells using the «tube assay» and induction ofinducing differentiation in a specialized medium.
   Results. We have found that the majority of Sca-1+ rcVPCs express the urokinase receptor and endothelial cell markers on their surface and are capable of proliferation and integration into the newly formed vessels in the injured area, indicating their possible involvement in thecontribution to vascularization process after infarction. After acute ischemic injury, the accumulation of vasculogenic progenitor cells (8+2 and 27+7 cells per visual field, respectively; P = 0.032) and vascularization processes (85+11 and 166+25 capillaries per visual field, respectively; P = 0.033) were observed in myocardium of uPAR-/- animals, compared with wild-type animals. Our studies demonstrated that Sca-1+ rcVCPs derived from uPAR-/- murine hearts demonstrated a reduced ability to form capillary-like structures and endothelial differentiation compared with Sca-1+ rcVCPs from hearts of wild-type mice.
   Conclusion. Thus, uPAR deficiency may lead to impaired vasculogenic properties of Sca-1+ rcVCPs, which is likely due to the loss of regulatory influence of specific ligands and the ability to interact with signaling mediators such as integrins. From the viewpoint of regenerative medicine, the modulation of uPAR activity can be considered as a potential targetpromising approach for targeted regulation of vasculogenic progenitor cells properties and postnatal angiogenesis.

Highlight

   The urokinase-type plasminogen activator receptor is involved in the regulation of the angiogenic properties of Sca1+ vasculogenic progenitor cells.