[Comparative efficacy of various methods of treatment of chronic venous oedema in real clinical practice]. / Sravnitel'naia éffektivnost' razlichnykh metodov lecheniia khronicheskogo venoznogo oteka v real'noi klinicheskoi praktike.

AIM: The study was aimed at assessing efficacy and safety of micronized purified flavonoid fraction (MPFF, Detralex) in comprehensive treatment of chronic venous oedema induced by lower limb varicose veins. PATIENTS AND METHODS: We performed a post hoc analysis of the results of treatment of 708 patients included into the observational programme VAP-PRO-C3 (ClinicalTrials.gov. NCT03722836). These patients, depending on the type of treatment, were divided into 8 subgroups: MPFF (n=32); MPFF + compression (n=145); MPFF + compression + topical treatment (n=158); MPFF + compression + topical treatment + endovasal laser coagulation (n=197); MPFF + endovasal laser coagulation (n=3); MPFF + compression + endovasal laser coagulation (n=152), patients not receiving MPFF (n=16); MPFF + topical treatment (n=2). Due to paucity of the participants, from the subsequent analysis we excluded the groups MPFF + endovasal laser coagulation, patients not receiving MPFF (n=16) and MPFF + topical treatment. All further statistical data are shown for the remaining 687 patients. RESULTS: Comparing the groups of patients undergoing conservative treatment alone and those subjected to surgical intervention demonstrated no statistically significant differences in dynamics of crural oedema. In both groups at every subsequent visit there was a statistically significant decrease in the ankle volume (p<0.001). During the whole period of follow up the crural volume in patients from the group of conservative treatment totally decreased by 0.201±0.158 L and in the operated patients by 0.236±0.189 L (p=0.021). The QOL assessed by the CIVIQ-14 global index score statistically significantly improved in the unoperated patients from 31.5±19.2 to 12.0±10.1 (p<0.001). In the operated patients, the baseline and final values of the QOL of the global index score amounted to 33.4±17.8 and 7.7±9.2, respectively (p<0.001). In the groups with and without topical treatment, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 28.5±17.4 and 36.2±18.6, respectively. During the follow-up period, we observed statistically significant positive dynamics of all parameters of quality of life. The final visit demonstrated improvement of the CIVIQ-14 global index score to 9.4±9.2 in patients without topical treatment and 10.1±10.4 in those receiving topical treatment (p=0.367), with the mean value of this parameter during treatment in both groups decreased significantly (p<0.001). A statistically significant decrease in the ankle volume in both groups was registered at every visit, finally amounting to 0.223±0.166 L and 0.248±0.174 L (p=0.118) for patients not receiving and receiving topical treatment, respectively. In groups of patients not receiving and those receiving compression therapy, the baseline values of the QOL assessed by CIVIQ-14 global index score amounted to 21.4±14.2 and 33.1±18.5 (p<0.001), respectively. At the final visit, these indices statistically significantly (p<0.001) decreased to 7.3±9.1 and 9.9±9.9 (p=0.106). Compared with the baseline values, the ankle volume at the final visit in groups of patients with and without compression therapy statistically significantly decreased by 0.187±0.14 L and 0.238±0.17 L respectively (p=0.204). During the study, there were no adverse events related to the administration of MPFF and use of Detragel. CONCLUSION: MPFF and Detragel appear to be effective and safe components of comprehensive conservative therapy of chronic oedema induced by primary varicose veins of lower extremities.

[Efficacy of micronized purified flavonoid fraction in treatment of chronic venous oedema]. / Éffektivnost' mikronizirovannoi ochishchennoi flavonoidnoi fraktsii pri lechenii khronicheskogo venoznogo oteka.

AIM: The purpose of the study was to assess efficacy and safety of using in real clinical practice micronized purified flavonoid fraction (Detralex) in patients with chronic venous oedema. PATIENTS AND METHODS: The study enrolled a total of 708 patients presenting with chronic venous disease, belonging to C3EpAsPr according to the CEAP classification (chronic venous oedema), who. depending on the accepted clinical practice by expert physicians were prescribed compression and phlebotropic therapy, as well as undergoing surgical interventions. The main criteria for efficacy of the micronized purified flavonoid fraction included the dynamics of chronic venous oedema, vein-specific symptoms, as well as the main parameters of quality of life. Assessment was made using visual analogue scales, the vein-specific questionnaire CIVIQ-14, and the method of discs for measuring the volume of the crus. RESULTS: The obtained findings demonstrated significant positive dynamics of the main vein-specific symptoms assessed by a visual analogue scale. When comparing between the visits of recruitment into the study and its termination the feeling of heaviness in calves decreased form 5.38±2.19 cm to 1.56±1.56 cm (p<0.001), pain in the calf diminished from 4.24±3.39 cm to 1.12±1.37 cm (p<0.001), feeling of oedema dropped from 5.68±2.44 cm to 1.38±1.59 cm (p<0.001), severity of nocturnal cramps fell from 2.46±2.30 cm to 0.43±1.01 cm (p<0.001), and intensity of skin inching from 1.46±2.06 cm to 0.43±1.01 cm (p<0.001). Positive dynamics of venous-specific symptoms appeared to be accompanied by significant improvement of all dimensions of quality of life according to the CIVIQ-14 scale: by the pain scale from 41.0±19.1% to 12.8±11.6% (p<0.001), by the physical condition scale - from 31.6±23.8% to 11.1±15.4% (p<0.001), by the psychological state scale - from 24.5±21.1% to 5.7±9.0% (p<0.001). The global index of quality of life also improved significantly from 32.4±18.5% to 9.9±9.9% (p<0.001). The results of the intervention along all the examined parameters (external appearance, possibility of wearing various clothes and increasing the quality of the self-performed work, to improve both interactions with surrounding people and the social activity and rest) turned out better than expectations form an intervention. The volume of the crus as the main criterion over the period of follow up averagely by the group decreased from 3.07±0.84 to 2.78±0.80 litres (p<0.001). A significant decrease in the calf volume from 3.03±0.87 to 2.77±0.85 litres was observed in 288 patients who during the follow up period were not subjected to surgical interventions, with no significant differences in the dynamics of chronic venous oedema revealed between the operated patients and those having received conservative treatment alone. DISCUSSION: According to a meta-analysis, the micronized purified flavonoid fraction (Detralex) turned out to possess better parameters in relation to therapy of chronic venous oedema as compared with other phlebotropic agents. Therefore, it appears absolutely logical to predominantly use the micronized purified flavonoid fraction in real clinical practice in patients with the CEAP C3 clinical class, which was registered in our study. An important result was also the fact that within the specified terms of follow up surgical intervention demonstrated no significant advantage over conservative therapy alone in treatment of chronic venous oedema. Moreover, conservative treatment in the form of a combination of compression and phlebotropic therapy demonstrated a dynamic decrease in the volume of the affected extremity with a probable transition of the CEAP C3 clinical class to C2. CONCLUSION: The micronized purified flavonoid fraction (Detralex) at a standard daily dose of 1000 mg in a combination with compression therapy irrespective of the surgical intervention performed resulted in a significant dynamic decrease in the volume of the calf in patients with chronic diseases of lower limb veins (C3EpAsPr according to the CEAP classification). An anti-oedematous effect of the micronized purified flavonoid fraction (Detralex) in a combination with compression manifests itself during the entire period of treatment.

[Local drugs in treating and decreasing the incidence of adverse reactions after sclerotherapy of telangiectasia]. / Mestnye preparaty v lechenii i snizhenii chastoty razvitiia nezhelatel'nykh reaktsii posle skleroterapii teleangiéktazov.

AIM: The purpose of the study was to assess efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® in decreasing the incidence and treatment of the most common local adverse reactions in patients after endured sclerotherapy of reticular veins and telangiectasias. PATIENTS AND METHODS: Our open prospective observational study included a total of sixty 18-to-35-year-old female patients who after undergoing standardized sclerotherapy of reticular veins and telangiectasias on symmetrical portions of lower limbs were given a tube of heparin sodium gel 1000 IU/g or Detragel® to be applied onto the skin of one (left) lower limb in the projection of the sclerotherapy-exposed vessels 2-3 times daily for 10 days followed by putting on a compression class 2 (RAL standard) stocking. The women were allowed to use only the paired stocking on the contralateral extremity. Efficacy and safety of heparin sodium gel 1000 IU/g and Detragel® were evaluated based on the incidence of typical adverse reactions (ecchymoses, phlebitides, hyperpigmentation and neovasculogenesis), as well as on the patient's subjective perceptions. RESULTS: The use of heparin sodium gel 1000 IU/g and Detragel® in addition to compression after sclerotherapy of reticular veins and telangiectasias significantly and comparably decreased the incidence and accelerated the resolution of ecchymoses and phlebitides associated with phlebosclerosing treatment. The Detragel® group patients were found to develop hyperpigmentation or neovasculogenesis significantly less often as compared with the heparin sodium gel 1000 IU/g group women. What is more, using Detragel® was not accompanied by hyperkeratosis, pruritus or formation of a sticky film, the events, however, observed while applying heparin sodium gel 1000 IU/g. CONCLUSION: The use of Detragel® or heparin sodium gel 1000 IU/g for 10 days additionally to compression significantly decreased the incidence of typical undesirable reactions associated with sclerotherapy of reticular veins and telangiectasias. The Detragel® group women turned out to have lower incidence of hyperpigmentation and neovasculogenesis. Besides, Detragel® demonstrated better organoleptic properties.

[Perioperative administration of micronized purified flavonoid fraction in endovascular treatment of varicose disease]. / Perioperatsionnoe primenenie mikronizirovannoi ochishchennoi flavonoidnoi fraktsii pri éndovaskuliarnom lechenii varikoznoi bolezni.

AIM: The study was aimed at assessing efficacy and safety of using a micronized purified flavonoid fraction in the perioperative period in patients scheduled for endovascular surgical intervention for CEAP clinical class C2 lower limb varicose veins. PATIENTS AND METHODS: This study enrolled a total of 1519 patients with CEAP C2a,sEpAs (primary varicose vein with valvular incompetence of the great and/or small saphenous vein) who were subdivided into two groups. Group One included 1039 patients who in the perioperative period were prescribed a micronized purified flavonoid fraction at a daily dose of 1000 mg and who continued therapy, including visit 4. Group Two was composed of 480 patients taking no venoactive agents. The main criterion for assessing efficacy of the micronized purified flavonoid fraction was the incidence rate of typical adverse events in the compared groups of patients after surgical intervention. RESULTS: The patients receiving the micronized purified flavonoid fraction were found to have adverse events significantly less often as compared with those in the control group: ecchymosis 7.1 versus 11.0% (p=0.01), haematoma 0.5 vs 1.3% (p=0.1), paresthesia 0.5 vs 1.7% (p=0.02), thrombophlebitis 0.2 vs 0.6% (p=0.2), pigmentation 0.6 vs 3.3% (p=0.001), heat-induced thrombosis 0.3 vs 1.3% (p=0.02). The total incidence rate of adverse events in patients receiving and those not receiving the micronized purified flavonoid fraction amounted to 7.6 vs 15.0%, respectively (<0.001). DISCUSSION: The micronized purified flavonoid fraction prescribed in the perioperative period, owing to a pluripotent mechanism, adapts the venous system and microcirculatory bed of the lower extremities to operative stress, decreasing the anti-inflammatory response to endovascular intervention, lowering thereby the incidence of undesirable events. CONCLUSION: Prescription of the micronized purified flavonoid fraction in the perioperative period ensures a significant decrease in the incidence of typical adverse events developing after endovascular surgical treatment for CEAP clinical class C2 varicose veins and may be recommended for real clinical practice.

[Detralex-phlebosclerosing treatment. Results of the national multicenter follow up programme VEIN ACT PROLONGED-C1]. / Detraleks - fleboskleroziruiushchee lechenie. Rezul'taty natsional'noi mnogotsentrovoi nabliudatel'noi programmy VEIN ACT PROLONGED-S1.

Presented herein are the results of the observational follow up study programme dedicated to the assessment of appropriate use of adjuvant therapy with Detralex while carrying out phlebosclerosing treatment in patients suffering from dilated intradermal veins (clinical class C1 according to the CEAP classification). A conclusion was drawn that administration of Detralex for 60 days decreased the incidence rate of typical undesirable side events after phlebosclerosing therapy, thus making the use of this drug appropriate in routine clinical practice.

[Adjuvant phlebotrophic therapy and its effect on anti-inflammatory response after sclerotherapy]. / Ad'yuvantnaya flebotropnaya terapiya i ee vliyanie na provospalitel'nyi otvet posle skleroterapii.

The study was aimed at evaluating the degree of the systemic and local inflammatory reaction after sclerotherapy, as well as the effect of micronized purified flavonoid fraction (Detralex) thereupon. The study comprised a total of 60 female patients presenting with reticular veins and telangiectasias (clinical class C1 according to the CEAP classification). The patients were subdivided into two groups, each comprising 30 women. The Study Group patients two weeks prior to the forthcoming sclerotherapy had been taking Detralex prescribed at a daily dose of 1,000 mg whose administration was prolonged by not less than 2 months after the procedure. The Control Group patients received no drug. We determined the systemic and local levels of inflammatory markers, anti-inflammatory cytokines and growth factors: C-reactive protein in a highly sensitive range, histamine, interleukin-1, tumour necrosis factor alpha and vascular endothelial growth factor. Patients in the Study and Control Groups on day 10 after sclerotherapy demonstrated a considerable increase in the levels of anti-inflammatory cytokines and inflammatory markers. At the same time, excess of the baseline levels of the parameters in patients taking Detralex was statistically significantly lower as compared with the Control Group patients: C-reactive protein - 6.0±0.9 mg/l vs 8.3±1.0 mg/l; histamine - 87.0±9.8 µg/l vs 156.9±33.9 µg/l; interleukin-1 - 5.9±0.4 pg/ml vs7.6±0.6 pg/ml; tumour necrosis factor alpha - 5.9±0.9 pg/ml vs 7.5±0.4 pg/ml; vascular endothelial growth factor - 252.3±26.0 pg/ml vs 325.1±47.7 pg/ml. A conclusion was made that microsclerotherapy with the use of low-concentration detergent drugs was accompanied by a local vein-specific inflammatory reaction whose degree may be diminished by means of prescribing micronized purified flavonoid fraction (Detralex) two weeks prior to and during the whole subsequent period of phlebosclerosing treatment in a standard daily dose of 1,000 mg.

[Recanalization of lower-limb deep veins as an index of efficacy of treatment for acute venous thrombosis]. / Rekanalizatsiia glubokikh ven nizhnikh konechnostei kak pokazatel' éffektivnosti lecheniia ostrogo venoznogo tromboza.

The authors analysed the results of examination and treatment of a total of 102 patients presenting with iliofemoral venous thrombosis. During treatment, ultrasonographic duplex scanning was used to determine the localization of the proximal margin of thrombotic masses, the time of appearing of the first signs of recanalization, its degree at various levels of the deep venous system, as well as alteration in velocity of the venous blood flow in the deep veins of the lower limbs. The dynamics of clinical symptoms was assessed by the visual analogue scale. Clinical and instrumental examination was performed on day 10, and then 1, 3, 6 and 12 months after the beginning of treatment. The patients were subdivided into three groups. Group One comprised 38 patients receiving therapy with low-molecular-weight heparin (enoxaprin) followed by switching to indirect anticoagulants (warfarin) combined with venotonics (original highly-purified diosmin 600 mg once daily). Group Two was composed of 33 patients receiving rivaroxaban at a dose of 15 mg twice daily for 3 weeks, followed by 20 mg once daily. Group Tree patients (n=31) were also given rivaroxaban according to the above-described standard regimen but in combination with venotonics (original highly-purified diosmin 600 mg once daily). The obtained findings showed that prescribing rivaroxaban to patients from the first day of the disease made it possible to considerably improve and accelerate the processes of restoration of patency of deep veins of lower extremities as compared with the patients taking vitamin K antagonists (warfarin). In patients receiving rivaroxaban, there were no cases of residual thrombotic occlusions of the major veins, and recanalization in three fourths of patients was assessed as good and in the remaining third as moderate. In the warfarin group, occlusion in the iliac veins was noted to persist persisted in 13% of patients, with good recanalization observed only in half of the patients. Addition of venotonics (original highly-purified diosmin) to anticoagulants from the first day demonstrated safety of this therapeutic regimen (with no cases of clinically significant haemorrhagic complications revealed) and its high efficacy as compared with monotherapy with rivaroxaban. A combination of diosmin with rivaroxaban turned out more efficient than a combination of diosmin with warfarin.

[Comparative assessment of antiaggregant efficacy of acetylsalicylic acid and clopidogrel in peripheral atherosclerosis].

Presented in the article are the results of studying antiaggregate activity of acetylsalicylic acid and clopidogrel in a total of 36 patients suffering from various-severity chronic arterial insufficiency of lower limbs on the background of atherosclerosis obliterans. The study was conducted prior to treatment for correct selection of a particular antiplatelet agent. The obtained results showed that clopidogrel was not always more efficient than acetylsalicylic acid, since there is individual sensitivity of each patients to a particular antiplatelet agent. Therefore, an individual approach is necessary to conservative therapy of arterial insufficiency of lower limbs. For some patients it is preferable to administer clopidogrel, for others - acetylsalicylic acid. In a series of cases combined treatment is justified, while some patients having low sensitivity to both acetylsalicylic acid and clopidogrel require careful selection of alternative agents influencing other thrombocyte receptors.

[Peculiarities of arterial reconstructions in pyonecrotic lesions of lower limbs].

Presented herein are the results of treating a total of sixty patients suffering from atherosclerosis obliterans of the lower limbs with degree IV chronic ischaemia according to the Fontain-Pokrovsky classification and accompanied by pyonecrotic alterations. The patients were subdivided into two clinically matching groups, each comprising 30 subjects. All patients after two-week conservative preparation underwent various reconstructive surgical operations performed on major arteries of the lower limbs. The local preoperative treatment was of two different types, i. e. consisting of Levomecol ointment used in the control group patients and Metrogyl 1% topical gel applied in the study group patients. Sampled before treatment, inoculations of the wound discharge demonstrated predominantly anaerobic flora in all patients, with the number of bacterial strains having dramatically decreased once Metrogyl gel 1% had been used, whereas application of Levomecol did not significantly influence the structure of the microbial profile. Following surgical treatment we had to perform high amputation of the lower limb in 5 patients of the control group, whereas in the study group patients only one patient required amputation at the foot level. Hence, prior to carrying out reconstructive vascular interventions in patients presenting with pyonecrotic lesions of lower extremities it is preferable to perform debridement of the necrotic foci using topical antibacterial agents, one of which may be Metrogyl 1% gel.

Within-host viral evolution in a heterogeneous environment: insights into the HIV co-receptor switch.

A virus infecting a host faces a heterogeneous and a spatially structured environment. Using a mathematical model that incorporates two types of target cells and spatial structuring, we investigate conditions for viral within-host diversification. We show that branching occurs for a wide range of parameters but that it always requires some spatial structure. Applying our model to the case of HIV, we show that it captures three main properties of the 'co-receptor switch' observed in many HIV infections: the initial dominance of virus strains that infect CCR5(+) cells, the late switch in some (but, importantly, not all) HIV infections and the associated drop in the number of uninfected T-cells. This suggests that the co-receptor switch could result from gradual adaptation of the virus population to target cell heterogeneity. More generally, we argue that evolutionary ecology can help us better understand the course of some infections.

[Prediction of remote results after surgical management of patients presenting with atherosclerosis obliterans of the lower-limb arteries].

Forecasting the development of implants' narrowing appears to be one of the most important problems encountered in vascular surgery today. The present study was therefore undertaken to work out a comprehensive diagnostic methodology making it possible to reliably predict the development of stenosis of vascular anastomoses during the postoperative period in patients presenting with atherosclerosis obliterans. The work was based upon the findings obtained by examining a total of seventy-nine patients diagnosed with atherosclerosis obliterans of the lower-limbs arteries, also including assessment of a large number of haemodynamic and immunological parameters both before and after reconstructive vascular interventions. The study showed substantial dynamics of a series of immunological and haemodynamic indices on the background of the operation and during the postoperative period. Based on the mathematical processing of the obtained data, the authors managed to reveal the factors playing a leading role in the development of stenosis, having also worked out a prognostic algorithm making it possible with high reliability to predict the development of stenosis of arterial anastomoses.

Relative effects of barrier precautions and topical antibiotics on nosocomial bacterial transmission: results of multi-compartment models.

Nosocomial bacterial infections in critically ill patients are generally preceded by asymptomatic carriage (i.e. colonization) at one, or even several, body sites such as the skin, the gastro-intestinal and the respiratory tract. Different routes of transmission between the colonized sites create a complex epidemiology, which is additionally complicated by the smallness of the patient population size and the rapid patient turnover, characteristic for intensive care units (ICUs). Naturally occurring large fluctuations in the prevalence of colonization make it very difficult to determine the efficacy of control measures that aim to reduce the prevalence of antibiotic-resistant bacteria in ICUs. Theoretical models can sharpen our intuition through carefully designed thought experiments. In this spirit, we introduce and investigate two models that incorporate the fact that patients may be colonized at multiple body sites. Our study can be applied to several pathogens commonly found in ICUs, such Pseudomonas Aeruginosa, enteric Gram-negative bacteria, MRSA and enterococci. We evaluate the effects of barrier precautions (improved hygiene, use of gloves and gowns, etc.) and of administration of nonabsorbable antibiotics on the prevalence of colonization in ICUs and find that the effect of the controversial, though widely used, antibiotic prophylaxis can only be substantial if the patient-to-patient transmission has already been reduced to a subcritical level by barrier precautions. Taking into account that the very use of antibiotics may increase the selection for resistant strains and may thereby only add to the ever increasing problem of antibiotic resistance, our findings hence represent a firm theoretical argument against the routine use of topical antimicrobial prophylaxis for infection control.

[Preoperative care of microcirculatory vessels in patients with lower limb arteriosclerosis obliterans].

The paper analyses diagnosis and treatment outcomes for 20 men aged from 55 to 76 with lower limb arteriosclerosis obliterans. Based on exhaustive laboratory and instrumental diagnostic data the authors conclude that 10-days course of Vazaprostan (20 mkg per day) for patients with IIb stage of chronic lower limb arterial insufficiency yields not only improvement in tissue metabolism, but a reduction of peripheral vascular resistance as well. Thus such therapy can be used for preoperative care before reconstructive vascular interventions in order to reduce the risk of implant thrombosis in early postoperative period.

[Effect of intestinal decompression with intubation on portal and systemic bacteremia in patients with peritonitis]. / Vliianie zondovoi dekompressii kishechnika na portal'nuiu i sistemnuiu bakteremiiu u bol'nykh s peritonitom.

Examination of 55 patients, who underwent operation for generalized peritonitis of various etiology, included comparative appraisal of the degree of portal and systemic bacteremia and the leukocytic index of intoxication in patients with and those without nasointestinal intubation. It was found that the microflora of a paretic intestine was one of the most important factors of intoxication in patients with peritonitis in the postoperative period. Nasointestinal intubation in this case proved to be an effective method for reducing the degree of portal and systemic bacteremia and ensured a significant decrease of the degree of intoxication as compared to that in the control group.

[Hepatic insufficiency in pancreonecrosis]. / Pechenochnaia nedostatochnos't pri pankreonekroze.

The examination of 225 patients has shown that the syndrome of hepatic insufficiency associated mainly with hyperperfusion of the liver is developing in pancreonecrosis. The regional infusion therapy is recommended for prophylactics and treatment of hepatic insufficiency.