Vol 100, No 1 (2019)

Специальный доклад
Essential medicines for universal health coverage
Wirtz V.J., Hogerzeil H.V., Gray A.L., Bigdeli M., Joncheere C.d., Ewen M.A., Gyansa-Lutterodt M., Jing S., Luiza V.L., Mbindyo R.M., Möller H., Moucheraud C., Pécoul B., Rägo L., Rashidian A., Ross-Degnan D., Stephens P.N., Teerawattananon Y., ‘t Hoen E., Wagner A.K., Yadav P., Reich M.R.

Abstract

Основные лекарства удовлетворяют приоритетные потребности населения в области здравоохранения. Политика, основанная на концепции основных лекарств, имеет решающее значение в улучшении здоровья и достижении устойчивого развития. Цель устойчивого развития 3.8 конкретно упоминает важность «доступности безопасных, эффективных, качественных и доступных по цене основных лекарств и вакцин для всех» в качестве центрального компонента всеобщего охвата медицинской помощью (ВОМП), а цель устойчивого развития 3.b подчёркивает необходимость разработки лекарств для устранения постоянно возникающих пробелов в отношении лечения. Признание важности основных лекарств - не новость. В 1985 г. на конференции в Найроби по рациональному использованию лекарств представители правительств и другие заинтересованные стороны предложили всеобъемлющий комплекс мер по разработке политики в области основных лекарств. Через 30 лет была созвана «Комиссия журнала Ланцет (Lancet) по основным лекарствам» (далее Комиссия) для изучения следующих вопросов: Какого прогресса удалось достичь? Какие проблемы ещё остаются для решения? Какие уроки были извлечены для информирования будущих подходов? И как можно использовать политику в области основных лекарств для продвижения ВОМП и внесения вклада в повестку глобального устойчивого развития? В настоящем докладе рассмотрены эти вопросы с намерением репозиционировать политику в области основных лекарств в повестке глобального развития. Комиссия определила пять областей, имеющих решающее значение для политики в области основных лекарств: оплата корзины основных лекарств, обеспечение ценовой доступности основных лекарств, гарантия их качества и безопасности, мероприятия, способствующие их качественному использованию, и разработка недостающих (отсутствующих) основных лекарств. Комиссия позиционировала политику в области основных лекарств в контексте текущих глобальных дебатов о балансировании политики в области торговли и интеллектуальной собственности с правами человека, об обеспечении безопасности здравоохранения, укреплении систем здравоохранения, ориентированных на людей, и улучшении доступности основных технологий. Во всех областях политики особое внимание было уделено совершенствованию принципов равенства и справедливости в доступе, укреплению соответствующих институтов и созданию подотчётности. В каждой из определённых областей Комиссия сформулировала рекомендации к действию, подтвердив тем самым позицию политики в области основных лекарств в качестве центрального компонента глобального здоровья и здравоохранения и повестки развития.

Kazan medical journal. 2019;100(1):4-111
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Theoretical and clinical medicine
Expression level of androgen receptors in tumor tissue and its prognostic significance in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women
Kit O.I., Shatova Y.S., Tokmakov V.V., Novikova I.A., Ul’yanova E.P., Zlatnik E.Y.

Abstract

Aim. To evaluate the expression level and prognostic significance of androgen in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women.

Methods. We analyzed treatment outcomes of 60 cases of primary operable (T1-2N0M0) luminal breast cancer without overexpression of Her2/neu in postmenopausal women. The follow-up period was 5 years. All cases were divided by immunohistochemical method into luminal A (20 females) and luminal B (40 patients) subtypes. Along with the standard panel of immunohistochemical markers, expression of nuclear androgen receptors was measured in tumor tissues of all patients. Depending on the expression levels, patients with luminal A and B subtypes were divided into three groups: (1) with high, (2) moderate and (3) low or negative expression.

Results. Mean levels of androgen receptor expression in the nuclei of tumor cells in patients with luminal A subtype (57.3±5.9%) were higher than those of luminal B subtype (21.4±4.04%) by 62.7% (Mann-Whitney test, р=0.0026). In patients with luminal A subtype, the maximal accumulation of androgen receptors in the nuclei of tumor cells was 2.7 times higher (р=0.0023) than in patients with luminal B subtype. All cases diagnosed with the disease progression were characterized by low or negative level of nuclear androgen receptor expression.

Conclusion. Negative and low levels of androgen receptor expression in tumor tissues of postmenopausal patients with luminal primary operable breast cancer without overexpression of Her2/neu might be an independent factor associated with poor prognosis.

Kazan medical journal. 2019;100(1):112-116
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Novel methodological approaches in the system of early diagnosis of mastopathy with the use of computer dermography
Merkulova G.A., Pegova E.V.

Abstract

Aim. Optimization of the early detection of mastopathy on screening examinations due to the inclusion of data received with the use of computer dermography into the algorithm of complex diagnosis.

Methods. Integral evaluation of the health state was performed with the use of computer dermography as part of the diagnostic complex DgKTD-01. Fertile females (n=107) were divided into three groups. The study group (n=36) included the female patients with differentiated mastopathy. The control group (n=51) united the females complaining of discomfort in breasts, engorgement and tenderness. Parameters of the baseline level in the study group and the control group were studied; a prognostic model of mastopathy was developed. Comparative analysis of identified characteristics was performed in the comparison group.

Results. Females from the study group are in the group of adaptation risk with formation of premorbid states and diseases. The prognostic model of mastopathy was consistent disorder of the tonic activity of basic functions F2' and F3', functions F5-1', F5-2', F5-3' with the extremum in segments Th4-6 in regimen 2 which allowed determining females with the risk of the development of this pathology in comparison group.

Conclusion. Method of computer dermography serves as a methodological approach to revealing pre-nosological states which alllows using it as an additional non-invasive diagnostic screening test to determine mastopathy risk groups; the obtained results give ground to continue the further studies and improvement of the diagnosis on a large clinical material and to development of computed system for interpretation of the obtained data.

Kazan medical journal. 2019;100(1):117-124
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Role of genus Candida in etiology of nosocomial infections in a multidisciplinary surgical clinic
Atakishizade S.A.

Abstract

Aim. To establish the role of genus Candida in etiology of nosocomial infections in a multidisciplinary surgical clinic of Azerbaijan Medical University in 2014-2016.

Methods. Microbiological study was performed on the pathological material from 41 patients with nosocomial pneumonia, 40 patients with surgical site infections and 46 patients with nosocomial sepsis.

Results. Nosocomial infections developing in a multidisciplinary surgical clinic were found to depend on localization of nosocomial infections. In nosocomial pneumonia 24% of all isolated microorgamisms were fungi of genus Candida among which C. albicans was prevailing: 9 of 12 isolated strains of Candida (75%) were identified as C. albicans. In patients with surgical site infections 10.7% of all isolated microorganisms were fungi of the genus Candida among which C. albicans was also prevailing: 4 of 6 isolated strains of Candida (66.7%) were identified as C. albicans. The isolated strains of Candida were sensitive to the studied antifungal medicines (amphotericin B, fluconazole, voriconazole, ketokonazole, nystatin).

Conclusion. In nosocomial infection and surgical site infections Candida fungi constituted 10.7-24% of all microorganisms isolated from the patients; the isolated Candida fungi - causative agents of nosocomial infections - were not resistant to antifungal medicines (amphotericin B, fluconazole, voriconazole, ketokonazole, nystatin).

Kazan medical journal. 2019;100(1):125-129
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Efficacy of plasma exchange in patients with ischemia-reperfusion syndrome of the lower extremities
Zhigalova M.S., Pasechnik I.N., Kutepov D.E.

Abstract

Aim. Optimization of treatment of patients with critical lower limb ischemia in ischemia-reperfusion syndrome by a combination of infusion therapy and plasma exchange.

Methods. The study included 58 patients (48 men, 10 women) aged 52 to 87 years (mean age 67.1±6.2 years) operated for critical lower limb ischemia. In the postoperative period all patients received standard conservative treatment. Depending on its effectiveness, the patients were divided into two groups: group 1 (n=30) with a positive response to the treatment and group 2 (n=28) where plasma exchange was required. The indications for plasma exchange were a decrease in the rate of diuresis <0.5 ml/kg/h after the surgery for 4-6 hours, exceeding 5 times the normal values of creatine phosphokinase and 3 times the level of myoglobin.

Results. In 48% of patients (group 2), deterioration of the condition was registered, which manifested by deterioration of the state, increase in shortness of breath, decrease in the rate of diuresis. In the laboratory analysis of patients of group 2, attention was drawn to an increase in the level of myoglobin to 287.8±30.1 ng/ml, creatine phosphokinase activity to 1769.3±191.8 u/l, and that of lactate to 2.2±0.3 mmol/l. These parameters exceeded not only the normal values, but also the indicators of group 1. These changes indicated the manifestation of ischemia-reperfusion syndrome and the threat of acute kidney injury. Plasma exchange was accompanied by clinical improvement (decrease in shortness of breath, increase in the rate of diuresis) and pronounced positive dynamics of laboratory parameters. The inclusion of plasma exchange into the complex therapy of ischemia-reperfusion syndrome was accompanied by an increase in the rate of diuresis by 1.7 times (p <0.05), a decrease in the level of myoglobin by 3.1 times (p <0.05) and the activity of creatine phosphokinase by 2.8 times (p <0.05).

Conclusion. The use of plasma exchange during the first hours of clinical and laboratory manifestations of ischemia-reperfusion syndrome can prevent the development of fatal complications associated with the progression of this syndrome.

Kazan medical journal. 2019;100(1):130-134
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The effect of pharmacological correction with vitamin D on the cytokine response in children with atopic bronchial asthma
Allakhverdiyeva L.I., Sultanova N.G., Dzhafarova A.O.

Abstract

Aim. To study the state of the cytokine response in children with atopic bronchial asthma during pharmacological correction with vitamin D.

Methods. 63 children aged 3-17 years with atopic bronchial asthma of varying severity were examined. As a control group, 10 practically healthy children of the same age who had no history of allergic manifestations and no hereditary complications, were examined. The patients were divided into two groups matched by age: group 1 included 33 patients with mild (n=20) and moderate (n=13) bronchial asthma who received only basic anti-inflammatory therapy according to the severity of asthma; group 2 included 30 children with mild (n=18) and moderate (n=12) bronchial asthma who received basic anti-inflammatory therapy with vitamin D containing Tridrop [3 drops (1500 IU) per day for 1 month]. Patients were assessed for interleukin-2, -13 and -17 in the blood serum using a solid-phase enzyme-linked immunosorbent assay before and after treatment.

Results. The results obtained made it possible to clarify the changes in the cytokine spectrum in patients with atopic bronchial asthma in the course of the disease and the effect of pharmacological correction with vitamin D on it. The mean level of interleukin-2 in group 1 remained practically unchanged, the value of this cytokine was 2.77±1.51 pg/ml (p >0.05). In group 2, the mean interleukin-2 level increased to 5.07±1.02 pg/ml (p <0.01). The mean level of interleukin-13 in group 1 patients increased but not significantly, but in group 2 a decrease of interleukin-13 to 11.3±3.8 pg/ml (p <0.05) was registered. Interleukin-17 decreased by 2.6 times in group 2 (4.8±1.6 pg/ml, p <0.01). In group 1 there was no significant change in the level of interleukin-17, in all children it remained elevated (p >0.05).

Conclusion. Pharmacological correction with vitamin D on the background of basic anti-inflammatory therapy promotes the positive dynamics of the level of cytokines during the treatment of atopic bronchial asthma, which is related to the ability of vitamin D to regulate the function of Th2 and, as a result, to reduce the synthesis of interleukin-13 and -17, which participate in the pathogenesis of allergies and play an important protective role in bronchial asthma.

Kazan medical journal. 2019;100(1):135-139
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Experimental medicine
Distress symptoms development after a single episode of ultrasound exposure
Nosova M.N., Bondarchuk Y.A., Shakhmatov I.I., Matsyura A.V., Marshalkina P.S., Prokopets D.A.

Abstract

Aim. To study the influence of a single 24-hour episode of exposure to ultrasound waves propagating in air on microcirculation and parameters of hemostasis in rats.

Methods. The study was performed on 28 Wistar male rats. The experimental group was exposed to ultrasound for 24 hours. Geometric mean frequency was 25 kHz, acoustic pressure was 84.3 dB. Parameters of microcirculation of experimental rats received by laser Doppler flowmetry were compared with those of intact animals. Also comparative analysis of platelet and coagulation hemostasis, anticoagulant and fibrinolytic plasma activity was performed in rats from both groups.

Results. In experimental rats in response to 24-hour exposure to ultrasound, significant decrease of the studied active and passive factors of blood flow modulation occurred compared to those of intact animals: parameters of microcirculation, flax, endothelial and vasomotor wave amplitude, respiratory and pulse wave amplitude. When studying the parameters of hemostasis, significant hypercoagulation of extrinsic pathway and at the latest stages of coagulation which worsened with anticoagulant plasma activity inhibition along with decrease of fibrinolytic activity. The character of changes of hemostatic parameters confirmed the development of stress-reaction in rats registered during the study of microcirculation.

Conclusion. 24-hour ultrasound exposure causes significant disorders of microcirculation and unfavorable shifts in hemostasis - the signs of distress.

Kazan medical journal. 2019;100(1):140-146
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Pathomorphological picture of diabetic nephropathy in experimental diabetes mellitus
Filinova S.O., Zharikov A.Y., Bobrov I.P., Mazko O.N., Makarova O.G.

Abstract

Aim. To conduct a morphological study of the renal glomerulus in experimental diabetes mellitus and to study the pathomorphological features of the development of diabetic nephropathy.

Methods. The study was carried out on 25 male Wistar rats. Modeling of diabetes mellitus was carried out by intraperitoneal injection of streptozotocin at a dose of 65 mg/kg. For more selective modeling of type 2 diabetes, the rats of the control group were intraperitoneally administered a solution of cytoflavin, calculated by the dosage of nicotinamide 115 mg/kg. In the comparison group 1 ml of physiological solution was administered in a similar manner. On day 28 of the experiment, the animals were euthanized under ether anesthesia, the kidneys were extracted, purified and washed with physiological saline. The material was fixed in a 10% neutral formalin solution. Using the morphometric method, the area of the renal glomeruli and the area of the capillary lumens were measured, and after special computer processing of digital photographs, the total area of the vascular bed in the glomerulus and the area of mesangium in the renal glomerulus were estimated.

Results. After four weeks of experiment on rats with diabetes mellitus, some characteristic changes in the morphofunctional state of renal tissues developed: an increase of the area of renal glomeruli, thickening of the basement membrane of glomerular capillaries, an increase in the size of podocytes with a decrease of their number, and foci of nephrosclerosis.

Conclusion. Based on the results of the study, characteristic pathomorphological phenomena in the kidneys of rats with experimental diabetes mellitus were recorded, which indicate the development of diabetic nephropathy.

Kazan medical journal. 2019;100(1):147-152
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Cytoprotective effect of non-opioid leu-enkephalin analogue in primary culture of pulmonary fibroblasts in oxidative stress
Sazonova E.N., Lebed’ko O.A., Denisyuk G.A., Zhmerenetskiy K.V., Dobrykh V.A.

Abstract

Aim. Analysis of the cytoprotective effect of non-opioid leu-enkephalin analogue (Phe-D-Ala-Gly-Phe-Leu-Arg) in the primary culture of pulmonary fibroblasts in conditions of oxidative stress.

Methods. Pulmonary fibroblasts were incubated with the peptide of non-opioid leu-enkephalin analogue (Phe-D-Ala-Gly-Phe-Leu-Arg) in the concentration 0.1 μM for 6 hours. To simulate oxidative stress, 60 μM H2O2 was added to the culture medium for 2 hours. Experimental series included (1) «control»; (2) «non-opiate leu-enkephalin analogue» (the peptide was added to the culture medium 44 hours after the final passage); (3) «oxidative stress» (H2O2 was added to the culture medium 48 hours after the final passage); (4) «non-opiate leu-enkephalin analogue + oxidative stress» (the peptide and H2O2 were added to the culture medium 44 and 48 hours respectively after the final passage). In order to evaluate the generation of superoxide anion by pulmonary fibroblasts, the method of lucigenin-dependent chemiluminescence was used. Computer morphometry of the nucleo-nucleolar apparatus of fibroblasts stained with silver nitrate by the AgNOR method was used to assess the cell state: the area of fibroblast nuclei, the total nucleoli area in the nucleus, and the number of nucleoli in the nucleus were measured. These parameters correlate with the activity of anabolic processes in the cells.

Results. The effect of H2O2 on the primary culture of pulmonary fibroblasts caused an increase of superoxide anion generation by the fibroblasts, reduction of fibroblast nuclei size, decrease of nucleoli amount and size. Pre-incubation of pulmonary fibroblasts with a non-opioid leu-enkephalin analogue reduced the H2O2-induced generation of superoxide anion, corrected changes in the nucleo-nucleolar apparatus of fibroblasts caused by oxidative stress. In our previous studies, similar effect in the same model was shown for non-selective μ/δ-opioid receptor agonist peptide sedatin (dermorphin analogue). The mechanism of cytoprotective effect of non-opioid leu-enkephalin analogue may include the affinity of this peptide to nociceptin receptors (NOR receptors) that requires further studies.

Conclusion. The results of the study indicate a direct cytoprotective effect of the peptide Phe-D-Ala-Gly-Phe-Leu-Arg (non-opioid leu-enkephalin analogue) in oxidative stress.

Kazan medical journal. 2019;100(1):153-157
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Reviews
Optogenetics and photopharmacology - effective tools for managing cell activity using light
Bregestovski P.D., Zefirov A.L.

Abstract

Contemporary research has been enriched by the new directions in which the light plays a key role as a tool for modulation of cellular activity and invasive monitoring of intracellular ions and other components. The main advantages of these approaches are the possibilities to precisely control the intensity, spectral characteristics and durations of light signals in space and time. This review summarizes the key areas, optogenetics and photopharmacology, - directions that allow to control cellular activity with light. Optogenetics is the use of light-sensitive transmembrane proteins capable of exciting or inhibiting cellular activity under illumination by different wavelengths. In 2003 a light-sensitive protein canalo-rodopsine was isolated and cloned which is capable of inducing ion currents and changing cellular rest potential with its excitation under the blue light when embedded into the neurons or other cell types. Inhibition of cellular activity is caused by expression of other lightsensitive proteins - chloride or hydrogen pumps, or anion-selective ion channels. These principles turns out to be efficacious for the study of the functions of solitary cells and neural nets as well as for the control of living organisms behavior but their use in medicine is complicated because of necessary genetic manipulations. Photopharmacology is based on creating and using of chemical compounds changing conformations and/or activity under the light. Photochromic compounds with the use of photosensitive switches are capable of selective activation or inhibition of the activity of functionally important proteins - receptors, ion channels, enzymes, etc. The principles and the potential use of optogenetics and photopharmacology in the analysis of the neuronal functions and the perspectives for new approaches to treat some diseases of the nervous system are discussed.

Kazan medical journal. 2019;100(1):158-169
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Age-related changes of the vitreous body
Stebnev S.D., Stebnev V.S., Malov I.V., Malov V.M., Eroshevskaya E.B.

Abstract

Innovative advances in recent years in the study of pathological changes of the posterior segment of the eye including the use of optical coherence tomography which is considered the gold standard for diagnosing vitreoretinal interface pathology, not only significantly expanded the idea of the most prevalent lesions of the structure of posterior eye segment but also discovered absolutely new aspects of their pathology. The review emphasizes the spreading understanding of vitreous body, its age-related changes in the pathology of the posterior eye segment. Two main interrelated processes occurring in the vitreous body - synchysis and syneresis, gradually increasing with age, are considered. Synchysis process begins at the early age and by the age of 70 reaches 50% of the volume of the vitreous body in 70% of the population. Parallelly, syneresis provides strength and plasticity of the entire vitreous volume due to collagen involved in formation of fibrillar frame. An important role in maintaining a stable and viscoelastic structure of the vitreous body, belonging to hyaluronic acid, is discussed, the level of which remains relatively stable at any age due to its constant synthesis. The accumulated data on the structure of age-related and pathological biodegradation of the vitreous body demonstrates inevitable progression of this process leading to age-related posterior vitreous detachment, which is a detachment of the posterior cortical layers of the vitreous body from subjacent retina. Posterior detachment under the influence of age-related changes in the vitreous body has certain stages - from incomplete juxtafoveolar detachment to complete posterior vitreous detachment with clinical retinal changes corresponding to each stage (idiopathic macular holes, lamellar macular tears, macular fibrosis, vitreomacular traction syndrome, myopic foveoschisis). Complete posterior vitreous detachment usually does not cause anatomical retinal disorders and any clinical forms of its diseases, thus, it can be considered as a natural favorable outcome.

Kazan medical journal. 2019;100(1):170-174
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Medical cybernetics
Reference information in integral anamnesis development
Zarubina T.V., Koroleva Y.I., Rauzina S.E., Shvyrev S.L.

Abstract

The article is devoted to semantic content of integral anamnesis - basic part of national integrated electronic health record. Integral anamnesis is a formalized set of the most important clinical data of a patient aimed at safety and continuous medical care both emergency and elective care. A short review of international projects of implementation and trans border exchange of key information about a patient is presented. Information content of integral anamnesis is presented which is developed in our country and includes 15 main sections: disability, benefits, social factors, addiction and occupational hazards, significant vital parameters, blood types and rhesus factor, pathological reactions, vaccination and immunization, epidemiological anamnesis, significant (dispensary) diseases, surgical interventions, medical devices and implants, pregnancies and deliveries, current medications and non-drug treatment. Administration, structure, problems, readiness of reference materials for coding of information presented in integral anamnesis are described. At the moment most of the necessary reference materials are finished and available on the portal of normative-reference information of the Ministry of Health of the Russian Federation (http://nsi.rosminzdrav.ru/): 20 basic and 7 additional ones. At the current stage it provides interoperability of medical information systems in integral anamnesis. Such time-consuming reference books as surgical interventions, instrumental diagnostic studies, federal reference book of medications are being actively developed. The section «Epidemiological anamnesis of a patient» stays practically unformalized. The first step in this direction is development of a reference book of immunobiological medications for specific prophylaxis, diagnosis and treatment. The aim of the study of semantic interoperability for integral anamnesis was reached by development of 27 reference books posted on the federal portal of normative-reference information of the Ministry of Health of Russia; the next stage should be development of technologies of formation and upgrade of the information of integral anamnesis.

Kazan medical journal. 2019;100(1):175-186
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Obituary
Professor Mikhail Rafailovich Rokitskiy
 
Kazan medical journal. 2019;100(1):187-189
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Cochrane Review Summaries
Laparoscopic surgery compared to open surgery for suspected appendicitis
 

Abstract

Характеристика исследований. Мы включили 85 исследований с 9765 участниками. В 75 испытаниях сравнивали лапароскопическую и открытую аппендэктомию у взрослых. Оставшиеся 10 исследований включали только детей. Доказательства актуальны на февраль 2018 г.

Kazan medical journal. 2019;100(1):190
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Determining the optimal method of securely closing the base of the appendix during keyhole surgery after removal of the inflamed appendix
 

Abstract

Актуальность. Аппендицит - это воспаление аппендикса. Традиционное лечение этого заболевания предполагает операцию по удаления аппендикса, называемую аппендэктомией. В последние годы для этой операции всё чаще применяется хирургия минимального доступа («замочной скважины») - лапароскопическая аппендэктомия. Неясно, каким способом лучше всего закрывать оставшуюся культю во время лапароскопической аппендэктомии, чтобы избежать излияния содержимого кишечника. Традиционные подходы предполагают использование лигатур и кисетного шва. Однако в последние годы некоторые хирурги предпочитают использовать автоматизированные механические устройства вместо лигатур. Неясно, уменьшают ли эти устройства число осложнений во время лапароскопической аппендэктомии по сравнению с лигатурами.

Kazan medical journal. 2019;100(1):190-191
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Interventions for preventing upper gastrointestinal bleeding in people on intensive care units
 

Abstract

Характеристика исследований. Доказательства актуальны на август 2017 г. Мы включили 106 исследований с участием в общей сложности 15 027 человек в критических состояниях любого возраста и пола.

Kazan medical journal. 2019;100(1):191-192
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