Метаболизм и микроструктура стенки тонкой кишки у пациентов с колоректальным раком

RELEVANCE In patients with colorectal cancer (CRC), the normal small intestine, located outside the pathological focus, undergoes changes that may be the cause of digestive dysfunction after radical surgery to remove the tumor.The assessment of metabolic and microstructural changes in the ileum mucosa in patients with colorectal cancer is necessary to correct the algorithms of postoperative therapy and enteral nutrition. Modern means of optical bioimaging are potentially capable of solving this complex diagnostic problem.AIM OF STUDY To study the features of metabolism and morphological structure of the wall of a conditionally normal small intestine in the mucosa in patients with stage 1–3 CRC using macro- FLIM and optical coherence tomography (OCT).MATERIAL AND METHODS The object of the study was the wall of the ileum (66 samples) from the mucosal side of patients with histologically confirmed CRC stages 1–3 with tumor location in the right sections of the colon. Eight samples were obtained from patients with stage 1 CRC, 38 samples were obtained from patients with stage 2 and 20 samples were obtained from patients with stage 3 tumor. The volume of surgical intervention is right-sided hemicolectomy with total mesocolonectomy, CME (D2 lymph node dissection). Fresh tissue samples were examined using fluorescent lifetime macroimaging (macro-FLIM ) and OCT, followed by histological analysis of the material.RESULTS According to a histological study in the small intestine of patients with stage 1 CRC, the mucosa is covered with a normal single-layer prismatic border epithelium. In the intestine samples of patients with stage 2 CRC, mucus hypersecretion with areas of fibrosis and vascular congestion was observed. At the 3rd stage of CRC, the mucous membrane of the small intestine was loose, with local thickenings, areas of fibrosis with severe leukostasis, and foci of atrophy. None of the samples showed histological signs of a malignant tumor.According to OCT data, in the mucous membrane of the small intestine in patients with the 1st and 2nd stages of CRC, the contours of the villi and, partially, the crypts were well visualized. The structure of the villi was smooth, not coarse, and the shape was regular. In patients with stage 3 CRC, the contours of the crypts and villi were indistinct. There were no differences in the OCT picture between histologic preparations in the 1st and 2nd stages of CRC: the structure of the villi of the small intestine was clear, the shape was unchanged. According to FLIM data, statistically significant differences were revealed in the mean fluorescence lifetime values of reduced nicotinamide dinucleotide (phosphate) NAD(P)H (τm) between 2nd and 3rd (p=0.031), 1st and 3rd (p=0.018) by CRC stages. At the 1st stage of CRC τm was 1.61 [1.30; 2.02] ns, at the 2nd stage 1.50 [1.36; 1.73] ns, at the 3rd stage 1.37 [1.22; 1.51] ns. The FLIM results suggest an increase in the role of glycolysis in enterocyte energy metabolism along with progression of the CRC stage.CONCLUSION In patients with cancer of the right colon, lesions of the microstructure of the mucous membrane were revealed in the ileum not affected by the malignancy. At the same time, the severity of microstructural disorders in the wall of the small intestine is associated with the stage of tumor development in the colon. Bioimaging technologies, namely, methods of optical coherence tomography and fluorescence lifetime macroimaging, made it possible to objectively display microstructural and metabolic disorders in the ileum wall. The data of optical colorectal tomography demonstrated differences in the structural picture of the intestinal villi in patients with stages 1–2 and 3 of colorectal cancer. Results of fluorescence lifetime macroimaging of the metabolic cofactor nicotinamide dinucleotide (phosphate) confirmed an increase in the role of glycolysis in the energy metabolism of enterocytes along with an increase in the stage of colorectal cancer. The identified disorders in the state of the small intestine develop in patients with colorectal cancer before surgery and are highly likely to be an important pathogenetic link of malabsorption in the postoperative period. If the hypothesis is confirmed, the developed algorithm for the complex diagnosis of microstructural and metabolic disorders in tissues will expand the possibilities for the rehabilitation of patients with cancer of the right colon.АКТУАЛЬНОСТЬ У пациентов с колоректальным раком (КРР) нормальная тонкая кишка, расположенная вне патологического очага, претерпевает изменения, которые могут быть причиной пищеварительной дисфункции после радикальной операции по удалению опухоли.Оценка метаболических и микроструктурных изменений в слизистой оболочке подвздошной кишки у пациентов с КРР необходима для коррекции алгоритмов послеоперационной терапии, энтерального питания. Современные средства оптического биоимиджинга потенциально способны решить эту сложную диагностическую задачу.ЦЕЛЬ Исследовать особенности метаболизма и морфологической структуры стенки условно нормальной тонкой кишки со стороны слизистой оболочки у пациентов с КРР 1–3-й стадий методами макро-FLIM и оптической когерентной томографии (ОКТ).МАТЕРИАЛ И МЕТОДЫ Объектом исследования являлась стенка подвздошной кишки (66 образцов) со стороны слизистой оболочки у пациентов с гистологически подтвержденным КРР 1–3-й стадий с локализацией опухоли в правых отделах ободочной кишки. 8 образцов получены у пациентов с 1-й стадией КРР, 38 образцов — у пациентов со 2-й стадией и 20 образцов — с 3-й стадией развития опухоли. Объем оперативного вмешательства — правосторонняя гемиколэктомия с тотальной мезо­колонэктомией — CME (лимфодиссекцией Д2). Свежие образцы ткани исследовали методами флуоресцентного время-разрешенного макроимиджинга (макро-FLIM) и ОКТ с последующим гистологическим анализом материала.РЕЗУЛЬТАТЫ По данным гистологического исследования в тонкой кишке пациентов с 1-й стадией КРР слизистая оболочка покрыта нормальным однослойным призматическим каемчатым эпителием. В образцах кишки пациентов со 2-й стадией КРР наблюдалась гиперсекреция слизи с участками фиброза и полнокровием сосудов. При 3-й стадии КРР слизистая оболочка тонкой кишки была рыхлой, с локальными утолщениями, участками фиброза с выраженным лейкостазом и очагами атрофии. Ни в одном из образцов не обнаружены гистологические признаки злокачественной опухоли.По данным ОКТ в слизистой оболочке тонкой кишки у пациентов с 1-й и 2-й стадиями КРР хорошо визуализировались контуры ворсинок и, частично, крипты. Структура ворсинок была гладкой, негрубой, а форма регулярной. У пациентов с 3-й стадией КРР контуры крипт и ворсинок были нечеткими. Различий в картине ОКТ между гистологическими препаратами при 1-й и 2-й стадиях КРР получено не было: структура ворсинок тонкой кишки была четкой, форма неизмененной. По данным FLIM выявлены статистически значимые отличия в показателях среднего времени жизни флуоресценции восстановленного никотинамиддинуклеотида (фосфата) НАД(Ф)Н (τm) между 2-й и 3-й (p=0,031), 1-й и 3-й (p=0,018) стадиями КРР. При 1-й стадии КРР τm составило 1,61 [1,30; 2,02] нс, при 2-й стадии — 1,50 [1,36; 1,73] нс, при 3-й стадии — 1,37 [1,22; 1,51] нс. Результаты FLIM предположительно свидетельствуют об увеличении роли гликолиза в энергетическом метаболизме энтероцитов вместе с увеличением стадии КРР.ЗАКЛЮЧЕНИЕ У пациентов с раком правых отделов ободочной кишки в не затронутой злокачественным поражением подвздошной кишке зафиксированы нарушения микроструктуры слизистой оболочки. При этом выраженность нарушений микроструктуры в стенке тонкой кишки связана со стадией развития опухоли в толстой кишке. Технологии биовизуализации, а именно — методы оптической когерентной томографии и флуоресцентного время-разрешенного макроимиджинга, позволили объективно отобразить нарушения микроструктуры и метаболизма в стенке подвздошной кишки. Данные оптической колоректальной томографии продемонстрировали различия в структурной картине ворсинок кишки у пациентов 1–2-й и 3-й стадий колоректального рака. Результаты флуоресцентного время-разрешенного макроимиджинга метаболического кофактора никотинамиддинуклеотида (фосфата) свидетельствовали об увеличении роли гликолиза в энергетическом метаболизме энтероцитов вместе с ростом стадии колоректального рака. Выявленные нарушения в состоянии тонкой кишки развиваются у пациентов с колоректальным раком до операции и с высокой вероятностью являются важным патогенетическим звеном мальабсорбции в послеоперационном периоде. В случае подтверждения гипотезы, разработанный алгоритм комплексной диагностики нарушений микроструктуры и метаболизма в тканях расширит возможности реабилитации пациентов с раком правых отделов толстой кишки

ASSESSMENT OF KNEE JOINT FUNCTION IN PATIENTS AFTER TOTAL KNEE ARTHROPLASTY USING THE KOOS SCALE

The goal was to evaluate the immediate results of treatment and knee function in patients after total knee replacement. Material and methods. The study included: questioning of patients, analyzing the medical records of inpatients, analyzing the features of surgical intervention and treatment during the postoperative period. We examined 81 patients with grade 3 gonarthrosis according to Ahlbäck. The patients underwent an examination of an orthopedic traumatologist with clinical assessment of their state by the KOOS scale (The Knee injury and Osteoarthritis Outcome Score). Results. A significant reduction in the pain syndrome was observed in the period from 30 to 180 days, ranging from 38.07 (11.1-50.0) points to 86.88 (72.2-97.2) points, respectively, which in turn speeded up the rehabilitation time after endoprosthetics (p <0.05). The severity of the pain syndrome in the period of 30-90 days after surgery was significantly lower in patients with rotation-endoprosthesis (50.0 - 66.4 points) than in those with modular endoprosthesis (38.07 - 60.6 points), respectively (p <0.05). The severity of symptoms throughout the period of observation of patients after surgery was significantly lower in patients with rotation-endoprosthesis (50.0 - 65.6 - 88.8 - 92.06 points) than in those with modular endoprosthesis (35.1 - 56.9 – 82.9 - 86.2 points), respectively (p <0.05). Conclusions. The evaluation of the knee joint function restoration after endoprosthetics using the KOOS scale is very detailed, which justifies its wider use in this category of patients

Mizernitskaya Olga Nikolaevna (to the 100^th anniversary of birth)

This article is dedicated to the 100th anniversary of the birth of Olga Nikolaevna Mizernitskaya, it is devoted to her contribution into the Russian pulmonology and allergology of children, it reveals little-known pages in the history of Russian pediatrics. Professional and creative path of Olga Nikolaevna reflects a difficult time. She made a significant contribution to the scientific development of pediatrics, pediatric allergology and pulmonology, for more than 16 years she was the main freelance pediatric allergologist and pulmonologist in Moscow, she brought up a galaxy of students, left an indelible mark in the history of the Scientific Research Clinical Institute of Pediatrics and in the pediatric science in general. The main areas of scientific, practical and organizational activities of Olga Nikolaevna Mizernitskaya were infectious-inflammatory (pneumonia) and allergic (bronchial asthma) lung diseases in young children. She published more than 130 scientific works, including a monograph and chapters in 7 monographs, a variety of methodological letters and recommendations, she prepared 6 candidates of medical sciences. The article presents the most significant aspects of the scientific and organizational activities of O.N. Mizernitskaya, bibliographic data, the paper notes her extraordinary merits of extremely responsive and kind person. Her difficult biography and creative path are consonant with the steps of the country and serve as an example for modern generations of physicians

The Anticoagulation in Patients with Atrial Fibrillation: Rivaroxaban and Warfarin

Aim. To study the effect of rivaroxaban compared with warfarin on the incidence of cardioembolic stroke and systemic thromboembolic complications (TEC), bleeding in patients with non-valvular atrial fibrillation (AF).Material and methods. Patients (n=126) older than 18 years, appealed to the Cardiology Clinic with non-valvular AF were included into an open non-randomized study. The patients were divided into 2 groups based on their socio-economic status: 77 patients received rivaroxaban and 49 - warfarin. The incidence of acute coronary syndrome, ischemic stroke and other TEC, bleeding as well as (only for patients taking warfarin) international normalized ratio (INR) and time in the therapeutic INR range were evaluated.Results. The incidence of ischemic stroke was not significantly different between groups, at the same time the incidence of other TEC was significantly higher in the warfarin group (0 vs 8%, p=0.011). The incidence of minor bleedings was significantly prevailed in warfarin group (0 vs 20%; p=0.0004). The time in the target INR range in the warfarin group was only 43%. 93.5% of patients continued to receive rivaroxaban after 9 months, and warfarin – 67.4% of patients.Conclusion. The results of our own clinical studies of rivaroxaban in patients with non-valvular AF have demonstrated efficacy comparable to that of warfarin. Rivaroxaban was superior to warfarin in safety

EFFICACY AND SAFETY OF ALBAREL IN PATIENTS WITH MILD, MODERATE AND SEVERE HYPERTENSION

The aim of the study was to evaluate the efficacy and safety (influence on carbohydrate, lipid and mineral metabolism, as well as nitrogen-excreting function of kidneys) of monotherapy with rilmenidine in patients with mild to moderate AH, as well as treatment of patients with severe AH as multiple combined treatment. 43 patients with essential AH I-HI degree, aged 22 to 79, were enrolled in this open label study after signing an informed consent form. Enrolled patients were divided into 2 groups. Group 1 included 20 outpatients. They received monotherapy with rilmenidine 1 mg daily. Duration of treatment was 12 weeks. Group 2 was comprised of 23 subjects admitted to an in-patient clinic. Those subjects received Albarel 1 mg or 2 mg daily as a component of multiple antihypertensive therapy. Albarel was administered 7-10 days following the admission to clinic as a second to fifth hypotensive drug. Albarel's combinations with diuretics, ACE inhibitors, calcium antagonists, beta-blockers. The result is - monotherapy with Albarel 1-2 mg daily allows to achieve target BP in 77, 8 % patients with mild to moderate AH. With Albarel as a component of multiple therapy target BP is achieved in 65, 2 % patients with severe AH. Effectively decreasing BP Albarel does not change its daily profile. It has no influence on renal function, carbohydrate metabolism, and electrolyte content of blood. Albarel is well tolerated. Adverse effects included mouth dryness and drowsiness, was noted in 2, 33 % cases and did not require drug withdrawal

A highly hydrolyzed formula based on whey protein with the prebiotics galactooligosaccharides and fructooligosaccharides effectively abolishes the symptoms of atopic dermatitis: Results of a multicenter open-label trial in Russia

Most cases of atopic dermatitis are caused by allergy to cow’s milk proteins in babies in their first year of life. Dietotherapy with highly hydrolyzed formulas is the basis for timely and adequate medical care to these children. The objective of the open-label multicenter prospective postregistration trial was to evaluate the efficacy of a formula based on the in-depth hydrolysis of whey proteins with the prebiotics GOS/lcFOS 0,8 g/100 ml for infants within their first year of life who received artificial nutrition and suffered from topical dermatitis presumably associated with allergy to cow’s milk proteins. The trial enrolled 51 babies aged 193,64 (SD 73,95) days with mild and moderate atopic dermatitis (SCORAD&lt;40). Results. During a 4-week dietotherapy cycle, there was abolishment of the skin symptoms of atopic dermatitis (SCORAD 26,66 (SD 9,19) and 6,63 (SD 4,36)) at the beginning and end of the trial and a reduction in the needs for topical glucocorticosteroids, zinc-containing topical agents and antihistamines (p&lt;0,01). The individual visual analogue scale efficiency of the dietotherapy was 8,53 (SD 1,51) and 8,72 (SD 1,20) scores as assessed by the parents and physicians, respectively. During the dietotherapy, the physiological rate of defecations was 1,88 (SD 0,94) times/day, the characteristics of stool significantly improved. The average daily formula intake was 786,13 (SD 169,21) ml. Weight-for-height in all the infants was in the normal range. Conclusion. The test formula is well tolerated and effective in more than 90% of the infants with atopic dermatitis presumably associated with allergy to cow’s milk proteins and ensures a child’s growth and development

GENERALIZED ANALYSIS OF MONOCLONAL ANTIBODIES TO IGE IN THE TREATMENT OF BRONCHIAL ASTHMA IN CHILDREN IN RUSSIAN FEDERATION

The article presents a generalized 2-year Russian experience in the application of monoclonal antibodies to IgE in children and adolescents with severe, resistant to standard treatment of bronchial asthma. Data on 65 patients treated with anti-IgE therapy with omalizumab within more than 6 months period in 6 centers of the Russian Federation from 2007 to 2010 were analyzed. The results of this analysis demonstrate the safety and high clinical effectiveness of anti-IgE-therapy in children and adolescents with severe uncontrolled atopic bronchial asthma. Full control of the disease or marked improvement can be achieved in 73% patients, the effect in most cases significantly increases during the first 6 months of treatment and becomes stable in the future, providing a good quality of life and normal lung function.Key words: bronchial asthma, anti-IgE-therapy, treatment, adolescents, children, quality of life, omalizumab

ОБОБЩЕННЫЙ АНАЛИЗ ПРИМЕНЕНИЯ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ К IGE В ЛЕЧЕНИИ БРОНХИАЛЬНОЙ АСТМЫ У ДЕТЕЙ В РФ

The article presents a generalized 2-year Russian experience in the application of monoclonal antibodies to IgE in children and adolescents with severe, resistant to standard treatment of bronchial asthma. Data on 65 patients treated with anti-IgE therapy with omalizumab within more than 6 months period in 6 centers of the Russian Federation from 2007 to 2010 were analyzed. The results of this analysis demonstrate the safety and high clinical effectiveness of anti-IgE-therapy in children and adolescents with severe uncontrolled atopic bronchial asthma. Full control of the disease or marked improvement can be achieved in 73% patients, the effect in most cases significantly increases during the first 6 months of treatment and becomes stable in the future, providing a good quality of life and normal lung function.Key words: bronchial asthma, anti-IgE-therapy, treatment, adolescents, children, quality of life, omalizumab.В статье представлен обобщенный 2-летний российский опыт применения моноклональных антител к IgE у детей и подростков с тяжелой, резистентной к стандартному лечению, бронхиальной астмой. Проанализированы данные 65 больных, получавших анти-IgE терапию омализумабом более 6 мес, в 6 центрах РФ с 2007 по 2010 гг. Результаты проведенного анализа свидетельствуют о безопасности и высокой клинической эффективности анти- IgE-терапии у детей и подростков с тяжелой неконтролируемой атопической бронхиальной астмой. Полного контроля болезни или выраженного улучшения удалось достичь у 73% пациентов, эффект в большинстве случаев значимо нарастает в первые 6 мес лечения и является стабильным в дальнейшем, обеспечивая хорошее качество жизни и нормальные показатели функции легких. Ключевые слова: бронхиальная астма, анти-IgE-терапия, лечение, подростки, дети, качество жизни, омализумаб. (Педиатрическая фармакология –2011; 8(2): 50-56

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

Aim: The Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method: An online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results: Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions: Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation