DNA Aptamers to Thrombin Exosite I. Structure-Function Relationships and Antithrombotic Effects.

DNA aptamers (oligonucleotides) interacting with thrombin exosite I contain G-quadruplex, two T-T, and one T-G-T loops in their structure. They prevent exosite I binding with fibrinogen and thrombin receptors on platelet surface, thereby suppressing thrombin-stimulated formation of fibrin from fibrinogen and platelet aggregation. Earlier, we synthesized original antithrombin aptamer RE31 (5'-GTGACGTAGGTTGGTGTGGTTGGGGCGTCAC-3') that contained (in addition to G-quadruplex) a hinge region connected to six pairs of complementary bases (duplex region). In this study, we compared properties of RE31 aptamer and its analogues containing varying number of bases in the duplex region and nucleotide insertions in the hinge region. Reduction in the number of nucleotides in the duplex region by 1 to 4 pairs (in comparison with RE31 aptamer) resulted in the decrease of the structural stability of aptamers (manifested as lower melting temperatures) and their ability to inhibit thrombin-stimulated fibrin formation in human blood plasma in tests of thrombin, prothrombin, and activated partial thromboplastin times. However, an increase in the number of bases by 1 to 2 pairs did not cause significant changes in the stability and antithrombin activity of the aptamers. Insertions into the hinge region of RE31 aptamer decreased its antithrombin activity. Investigation of RE31 antithrombotic properties demonstrated that RE31 (i) slowed down thrombin formation in human blood plasma (thrombin generation test), (ii) accelerated lysis of fibrin clot by tissue plasminogen activator in in vitro model, and (iii) suppressed arterial thrombosis in in vivo model. Based on the obtained data, RE31 aptamer can be considered as a potentially effective antithrombotic compound.

[Fast-track rehabilitation after anatomical lung resection: prospective single-center non-randomized trial]. / Prospektivnoe odnotsentrovoe nerandomizirovannoe issledovanie uskorennoi reabilitatsii patsientov posle anatomicheskikh rezektsii legkikh.

AIM: To present the results of fast track rehabilitation after anatomical lung resection. MATERIAL AND METHODS: Single-center prospective non-randomized trial has included patients for the period December 2014 - December 2016. Conventional protocol was applied in 124 patients, 58 patients after atypical lung resections or pneumonectomy were excluded from the study. Thus, there were 66 patients aged 61 (51; 67) years. Men/women ratio was 37:29. Lobectomy (n=55) and segmentectomy (n=11) were performed for lung cancer, metastatic injury and various inflammatory diseases in 53 (80.3%), 8 (12.1%) and 5 (7.6 %) cases, respectively. ASA risk score was II (16), III (46), IV (4). Video-assisted/open procedures ratio was 42 (63.6%) / 24 (36.4%). RESULTS: 30-day postoperative morbidity was 7.6% (5 out of 66 patients, 95% CI 3.3- 16.5). Pleural drainage tube was removed within the 1st postoperative day in 49 (74.2%) out of 66 patients. Prolonged insufficient aerostasis was observed in 3 patients followed by effective conservative treatment. Overall mortality was 3% (n=2, 95% CI 0.8- 10.4) due to pulmonary embolism and sudden cardiac death. Median of postoperative hospital-stay was 7 (6; 9) days without significant differences between groups of lobectomy and segmentectomy (p>0.05). CONCLUSION: Fast track rehabilitation protocol in thoracic surgery is safe and effective. Further studies are needed to justify early rehabilitation in high risk patients.

[Intraoperative fluid therapy during esophagectomy followed by repair]. / Intraoperatsionnaia infuzionnaia terapiia pri ézofagéktomii s odnomomentnoi plastikoi pishchevoda.

AIM: To optimize fluid therapy in transhiatal eshophagectomy by using of goal-oriented infusion therapy based on stroke volume variation. MATERIAL AND METHODS: Our trial enrolled 30 patients who underwent transhiatal esophagectomy followed by repair for the period 2011-2014. Patients were divided into 2 groups. The first group (LT) included 16 patients with liberal fluid therapy. The second group (GDT) consisted of 14 patients in whom goal-oriented fluid therapy was performed. Goal-oriented fluid therapy was implemented via stroke volume variation (SVV). RESULTS: Infusion rate was 6.7 ml/kg/h and 11.5 ml/kg/h in the main and control groups, respectively. Morbidity rate was 28.6% (n=4) and 62.5% (n=10) in the main and control groups respectively. Clavien-Dindo IV complications were lung atelectasis (n=2, 14%), pneumonia (n=1, 7%). Hydrothorax required puncture was noted in 1 (7%) case. Acute respiratory failure as complication IVa was in 1 (9%) patient. In the control group complications were registered in 10 (62.5%) patients. Complications I-II degree included lung atelectasis (n=4, 25%), cervical anastomosis failure (n=1, 6%); complications IVa were observed in 8 cases (50%). It was significant respiratory failure with reduced PO2/FiO2<300. Patients of the main group required less time for postoperative mechanical ventilation (120 [90-300] vs. 315 [215-810] min (p=0.02) and ICU-stay (0.83 [0.7-0.8] vs. 1.75 [1.25-2.75] (p=0.0022).

[SUPPORT LUNG VENTILATION IN COMPLEX OF ANESTETIC MANAGEMENT DURING HIGH TRAUMATIC OPERATIONS IN VASCULAR SURGERY.]

BACKGROUND: Rejection from prolonged mechanical ventilation with conversion to support ventilation modes during the surgery and subsequent immediate extubation at the end of the surgery could be the method ofprophylaxis ofpostoperative respiratory complications. THE AIM: To improve the results of surgical treatment of patients with infrarenal aorta injury due to the development and implementation to the anesthetic management complex the modes of support ventilation. MATERIALS AND METHODS: 2-staged clinical trial on patients undergoing surgery on infrarenal aorta was conducted. At the 1st stage patients were assessed for opportunity of immediate or early extubation and support ventilation initiation. At the 2nd stage support modes during the intraoperative ventilation were introducted into clinical praxis. RESULTS: Based on received data we concluded that not everyone patient needed intra- and postoperative mechanical ventilation in spite ofprolonged duration of the surgery and large surgical trauma. Inclusion in the protocol of anesthesia support ventilation strategy decreases requirement ofparalytic agents and their side effects. CONCLUSION: Applying the support ventilation modes during the anesthesia gives a chance of immediate and early extubation after the surgery and decreases the number of critical events and respiratory complications.