Vol 48, No 6 (2020)

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Full Issue


The revised pancreatitis etiology-based classification system TIGAR-O, version 2: adaptation for the Russian clinical practice

Bordin D.S., Kucheryavyy Y.A., Kiryukova M.A.


The discoveries in molecular genetics and breakthrough visualization techniques in the last 20 years have changed our understanding of the pancreatitis causes and biomarkers, expanded our knowledge on the pathophysiology of the disease, and promoted the development of new additional conservative treatments. From the practical perspective, the physician's comprehension of the etiology is of particular importance. It is for this reason that the activities to elaborate an etiology-based classification of pancreatitis have been already started since long ago. The first internationally acknowledged system was TIGAR-O checklist, introduced in 2001. Being innovative at the time, it structured our understanding of the etiology of chronic pancreatitis. The revised version (version 2) was published in 2019 and is less known to the Russian medical community, although from the authors' point of view, it has been substantially extended and structured to be maximally convenient and useful for physicians in routine medical practice. The review presents key provisions of the TIGAR-O, version 2 and recommendations for its adaption to the Russian clinical setting.

Almanac of Clinical Medicine. 2020;48(6):349-363
pages 349-363 views

The diagnostic and prognostic value of serological markers of inflammatory bowel diseases (a literature review)

Kuznetsova D.А., Lapin S.V., Shchukina O.B.


The diagnosis of inflammatory bowel disease (IBD) is based on a combination of clinical, endoscopic, histological, radiological and laboratory methods. However, conventional diagnostic methods are not always sufficiently informative in IBD, especially in the case of unclassified colitis, which necessitates the extension of standard diagnostic approaches. Currently, there is an actively search for non-invasive serological markers for early and differential diagnosis of IBD and for the assessment of activity and prognosis of Crohn's disease (CD) and ulcerative colitis (UC). Among the most interesting serological markers are anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), goblet cells antibodies (GAB) and pancreatic autoantibodies (PAB). The aim of this review is to assess the diagnostic and prognostic significance of ASCA, ANCA, GAB, PAB in CD and UC. The paper presents the summary of the data on the role of ASCA, ANCA, GAB and PAB in abnormalities of the immunological tolerance mechanisms to intestinal microflora and intestinal permeability in IBD. We discuss the results of the studies on the associations of ASCA with a complicated CD phenotype, its response to genetically engineered biological therapies, and the need for surgical intervention. The article describes the data on the association of ANCA to the risk of progression of left-sided UC to widespread (total) colon lesions resistant to hormonal therapy, and that of antibodies to DNA-lactoferrin complexes and proteinase 3 to primary sclerosing cholangitis. It has been noted that PAB may be a prognostic marker for ileocolitis, perianal lesions, extraintestinal manifestations and complicated CD, and GAB a  predictor of total UC with chronic persistent course. It should be emphasized that combined determination of ASCA, ANCA, GAB and PAB is highly informative, compared to the isolated detection of autoantibodies, for the differential diagnosis and prognosis of CD and UC.

Almanac of Clinical Medicine. 2020;48(6):364-374
pages 364-374 views

The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

Shcherbakova E.S., Sall T.S., Sitkin S.I., Vakhitov T.Y., Demyanova E.V.


The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

Almanac of Clinical Medicine. 2020;48(6):375-386
pages 375-386 views


Prognostic value of computed tomographic perfusion in the diagnosis of liver fibrosis and cirrhosis. Pilot study

Stashuk G.A., Smirnova D.Y., Podrez D.V.


Relevance: Most diffuse liver diseases lead to fibrosis over time with the risk of cirrhosis. With progressive fibrosis and cirrhosis of the liver both physical properties of the hepatic parenchyma and its hemodynamics change. The only reliable method for determining the stage of the disease is puncture biopsy and subsequent histological examination, but this method is invasive and associated with complications. Currently, the determination of the severity of cirrhosis is based on clinical data (the Child-Pugh scale) and elastography is considered to be the main non-invasive instrumental method. It lets reliably differentiate the initial fibrosis and cirrhosis of the liver, while the F2 and F3 stages according to the conventional METAVIR scale remain a "gray zone", as well as the differentiation of degrees of the severity of cirrhosis. In addition elastography has a  number of limitations. The main ones of which are operator dependence, apparatus dependence and the inability to determine functional changes in the liver. With the use of perfusion computed tomography (CT perfusion) it is possible to assess the functionality of the liver by quantifying changes in hemodynamics. The method applied measures the characteristics of blood flow in the tissue at a given scanning level by computed-tomographic data on the dynamics of the distribution of the contrast agent in the area of interest is collected, besides the type of liver perfusion is determined. This parameter is needed to assess the dynamics of treatment against the background of drug therapy.

Objective: To identify statistically significant parameters of CT perfusion to determine the severity of hemodynamic disturbances in patients with various stages of liver fibrosis and cirrhosis and to compare the values of parameters of liver CT perfusion with fibrosis according to the METAVIR conditional scale determined using elastography.

Materials and methods: 18  patients were included in this parallel pilot study. On the basis of clinical and laboratory data and the results of elastography, 10 of them were diagnosed with fibrosis and cirrhosis. The stages of fibrosis F1, F2 were determined in 3  patients; stages F3, F4  – in 7. In the group of patients with F3, F4, according to the METAVIR conditional scale, subgroups were distinguished depending on the severity of cirrhosis: compensated – 3 patients, subcompensated – 2, decompensated – 2. The control group consisted of 8 patients with organ diseases abdominal cavity not associated with liver damage. All patients underwent CT perfusion of the liver on a Philips iCT 256 using the following scan parameters: 80 KVp, 120 mAc, total scan time 56 s, and slice thickness 5.0 mm. Intravenously, bolus was administered to all patients with 50 ml of ioversol 350 mg/ml, the rate of administration was 3.8–4.0 ml/s, the time from the moment of administration of the contrast medium to the start of scanning was 6 s. After receiving a series of images, the data was processed on a Philips workstation. Quantitative analysis was carried out according to the following indicators: TTP (time to peak, s), BV (blood volume, ml/100 g), AP (arterial perfusion, ml/min/100 ml), PP (portal perfusion, ml/min/100  ml), TP (total perfusion, ml/min/100 ml) and HPI (hepatic perfusion index, %).

Results: In the control group of 8  patients, the perfusion values were: TTP 37.4±5.2  s, BV 16.1±5.0 ml/100 g, AP 25.0±7.5 ml/min/100 ml, PP 44.5±14.5 ml/min/100 ml, TP 70.1±14.9 ml/min/100 ml, HPI 70.1±14.9%. In 3 patients with F1, F2, according to the METAVIR conditional scale, the following statistically significant values (p<0.039) of perfusion indices were determined: BV 27.2±8.6  ml/100  g, AP 20.0±3.8  ml/min/100  ml; with compensated liver cirrhosis (n=3): TTP 46.2±1.7  s, BV 12.4±1.9  ml/100  g, AP 10.7±2.8 ml/min/100 ml, PP 37.3±5.2 ml/min/100 ml, TP 48.1±3.5  ml/min/100  ml, HPI 22.4±5.5%; subcompensated (n=2): TTP 43.0±3.2  s, BV 8.9±2.6 ml/100 g, AP 12.8±3.0 ml/min/100 ml, PP 27.7±9.0 ml/min/100 ml, TP 40.5±7.3 ml/min/100 ml; decompensated (n=2): BV 30.5±1.8 ml/100 g, PP 8.5±1.5 ml/min/100 ml, HPI 81.3±1.8%.

Conclusion: The preliminary results obtained confirm that CT perfusion can be used to predict and assess the severity of hemodynamic disturbances in patients with varying degrees of severity of cirrhosis and supplements clinical, laboratory and elastography data.

Almanac of Clinical Medicine. 2020;48(6):387-394
pages 387-394 views

Joint lesions in inflammatory bowel diseases: the analysis of the Moscow regional patient registry and a clinical case

Taratina O.V., Belousova E.A.


Rationale: Extraintestinal manifestations (EIM) of an inflammatory bowel disease (IBD) are a sign of its more severe course. Joint lesions are most common among IBD EIM.

Aim: To evaluate the prevalence and types of joint lesions in the population of IBD patients of the Moscow region.

Materials and methods: We performed a  retrospective analysis of medical files of the patients who were admitted to the Moscow Region Inflammatory Bowel Disease Center (MONIKI) for examination and treatment from August 1, 2019, to March 1, 2020. The study included 70 patients with confirmed diagnoses of IBD and confirmed or suspected involvement of the joints.

Results: Thirty six of 70 patients with IBD and EIM (51.43%) had been diagnosed with Crohn's disease (CD), and 34 (48.57%) with ulcerative colitis (UC). The CD group included more men (n=21, 58.33%), whereas their proportion in the UC group was 47.02% (n=16). The mean age at CD diagnosis in the UC and CD groups was comparable: 38.3±13.7  years in men with CD and 40.5±12.8 years in men with UC, 37.7±11.1 years in women with CD and 35.7±14.0 in women with UC. The most prevalent among all IBD patients were X-ray negative peripheral arthralgias. Among joint lesions confirmed by radiological diagnostics, sacroileitis was most prevalent both in all IBD patients (24.3%), as well as in the UC group (17.6%), whereas in the CD patients its frequency was the same as that of ankylosing spondyloarthritis (AS) (30.6% of the cases). AS ranked second in the prevalence of joint lesions in the UC group (8.8%) and all IBD (20%). Psoriatic arthritis was diagnosed only in the CD patients (2 / 36). We describe a clinical case of CD with AS, complicated with psoriatic rash, treated with a  monoclonal antibody to tumor necrosis factor alfa (anti-TNF-α).

Conclusion: Peripheral arthropathias were most prevalent among all joint lesions in the group studied. EIM mirror a more aggressive phenotype of the disease and higher glucocorticosteroids requirements. Administration of anti-TNF-α agents allows for the control of both intestinal IBD manifestations and of the joint syndrome. However, drug-associated skin adverse event can occur during treatment with this drug class. In such a case, it is possible to switch the biological therapy to another class of drugs that we have demonstrated with the given clinical example.

Almanac of Clinical Medicine. 2020;48(6):395-402
pages 395-402 views

The hardware method of biomaterial preparation for fecal transplantation

Shedoeva L.R., Chashkova E.Y., Karnoukhova O.G., Kogan G.Y.


Background: Nowadays fecal transplantation (FT) is considered as a  component of the treatment for a  wide range of disorders, including autoimmune diseases (ulcerative colitis, Crohn's disease, type 1 diabetes mellitus and insulin resistance, multiple sclerosis, psoriasis). High-quality preparation of the biomaterial is a necessary procedure that allows for long-time storage of the prepared fecal transplant at ultralow temperature conditions and it use as needed.

Aim: To optimize the method of preparation of the biomaterial for fecal transplantation and to evaluate its "survival" at different time points under cryopreservation conditions.

Materials and methods: A device for the preparation of donor fecal material for transplantation has been developed and proposed (the Russian Federation patent No. 2659417 from July 2, 2018). Donor fecal material (collected in a  sterile container on the same day of preparation in the morning), the solvent, and glycerol are homogenized automatically in the closed loop device and passed through a disposable filter with attached sterile hemocon container. Freezing at ultralow temperature (cryopreservation at -80 °C) allows for long time storage of this fecal graft. We studied the microbial composition of the obtained native substrate and samples that were cryopreserved at different time points (7 to 365 days).

Results: The proposed original method makes it possible to prepare the biomaterial for storage at a low temperature mode without any contact, in a  closed loop, for subsequent fecal transplantation within 6–12 months. The analysis of the fecal transplant at different time points has shown no qualitative and quantitative differences in the microbial composition between the native donor material and the freshly prepared filtrate. The biomaterial prepared according to the original method is stable for 12 months.

Conclusion: The proposed hardware method for preparing the biomaterial for fecal transplantation is easy to use and allows for the preparation of a  graft with minimal external microbial contamination, in contrast to the conventional method of donor material preparation by filtering fecal matter through gauze or coffee filters with manual assistance.

Almanac of Clinical Medicine. 2020;48(6):403-411
pages 403-411 views


Liver injury in COVID-19: two clinical cases

Nikitin I.G., Ilchenko L.Y., Fedorov I.G., Totolyan G.G.


COVID-19 (coronavirus disease 2019, a  disease caused by a  new coronavirus 2019) continues to threaten world public healthcare. Epidemiological data indicate that patients with metabolic disorders and chronic illnesses are most susceptible to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Potential factors for organ involvement include systemic hyperimmune-mediated inflammation due to the “cytokine storm”, cytopathic effects, hypoxia, drug toxicities, etc. In addition, SARS-CoV-2, by interaction with ACE2 (angiotensin-converting enzyme 2) receptors in the vasculature endothelium results in endothelial dysfunction, increased permeability, microcirculatory abnormalities, vascular thrombophilia and thrombus formation. The diagnosis of COVID-19 is confirmed by detection of SARS-CoV-2 RNA in biological samples and serum antibodies. The infection is associated with leukopenia and thrombocytopenia, increased С-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Abnormalities in functional liver tests seen in COVID-19 are associated with progression and severity of the infection. The mechanism of direct cytotoxicity due to active SARS-CoV-2 replication in hepatocytes are not fully understood and is likely to be related to potential proliferation of hepatocytes, liver injury in response to systemic inflammation, and development of drug hepatic toxicity. We present a  clinical case of drug-induced hepatitis in a  patient with COVID-19 treated with tocilizumab, an inhibitor of interleukin 6 receptors. Prolonged increase in blood enzymes after treatment cessation is likely related to a  longer half-elimination time of tocilizumab, which affects the oxidation-reduction system of liver cytochromes. Patients with chronic liver disorders are more vulnerable to clinical sequelae of СOVID-19, while the infection is frequently associated with hypoxia and hypoxemia due to severe pneumonia or the “cytokine storm”. In addition, patients who have been diagnosed with liver cirrhosis are at high risk of morbidity and mortality due to their higher proneness to infections, first of all, due to systemic immune deficiency that was demonstrated in the second clinical case. Decompensated liver cirrhosis is related not only to a higher risk of more severe COVID-19, but also to progression of chronic liver disease as such. To achieve effective results of causal and nosotropic therapy for COVID-19, it is highly significant to provide thorough clinical monitoring, tailored approach to the treatment of each patient with consideration of their comorbidities, immune status, and drug interactions.


Almanac of Clinical Medicine. 2020;48(6):412-421
pages 412-421 views


Early administration of genetically engineered biological agents for immune-mediated inflammatory diseases: opportunities and prospects. An experts’ opinion

Abdulganieva D.I., Bakulev A.L., Belousova E.A., Veselov A.V., Korotaeva T.V., Lila A.M., Loginova E.Y., Sokolovskiy E.V., Khobeysh M.M., Shapina M.V., Shchukina O.B.


Psoriasis (Ps), psoriatic arthritis (PsA), and inflammatory bowel diseases (IBDs) are characterized by a  progressive course and commonly result in disability. Therefore, their early diagnosis with the assessment of a  clinical phenotype and unfavorable prognostic factors and the timely initiation of therapy are important. The paper provides the expert consensus on the definition of the early stage of Ps, PsA, and IBDs, their treatment goals and main unfavorable prognostic factors. It also gives the rationale for the early use of biological agents in patients with immune-mediated inflammatory diseases.
Almanac of Clinical Medicine. 2020;48(6):422-436
pages 422-436 views


Choosing a method to perform an esophageal-intestinal anastomosis after complete removal of the stomach

Ivanov Y.V., Danilina E.S., Istomin N.P., Velichko E.A., Mamoshin A.V., Agibalov D.Y.


The paper reviews various methods of performing esophageal-intestinal anastomoses with complete removal of the stomach (gastrectomy). The main methods of manual and stapler stitching of the esophagus with the jejunum are described. Special attention is paid to detailing of techniques for the most commonly performed esophageal-intestinal anastomoses, with a  comparative assessment of the reliability of manual and stapler anastomoses. Given the large number of proposed methods to perform esophageal-intestinal anastomoses, it can be stated that no universal anastomosis yet exists. In laparotomy, a stapler suture is most commonly used to perform an esophageal-intestinal anastomosis with circular crosslinking devices, while the manual version implies one of the invagination techniques, or muff-like anastomosis (the Tsatsanidi K.N., Bondar G.V., Davydov M.I. procedure). With laparoscopic access, the anastomosis is performed with linear endoscopic crosslinking devices. The choice of a technique to perform an esophageal-intestinal joint remains with the operating surgeon and depends on his/hers experience, skills, individual intraoperative situation, and equipment of the operating unit.

Almanac of Clinical Medicine. 2020;48(6):437-444
pages 437-444 views

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