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Vol 13, No 3 (2021)

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Drug-induced diarrhea associated with antineoplastic drugs

Sychev D.A., Ostroumova O.D., Ziganshina L.E., Filippova A.V.


Diarrhea is the most common adverse reaction of anticancer drugs, as well as radiation therapy of the pelvic organs or abdominal cavity: the incidence of diarrhea of different seveity reaches 80% during chemotherapy and / or radiation therapy; one third of these patients develop severe diarrhea (3rd or 4th degree). Most often, drug-induced diarrhea occurs during chemotherapy, using 5-fluorouracil or irinotecan, taking new anticancer drugs from the classes of checkpoint inhibitors, monoclonal antibodies, tyrosine kinase inhibitors. The most common mechanisms underlying the development of drug-induced diarrhea are damage to the intestinal mucosa, impaired absorption of proteins, carbohydrates, fats, inflammation, a perverse immune response, microflora imbalance, and others.

Algorithms for the management of patients with severe diarrhea include suspension (grade 1-2, 3) or complete cessation (grade 4, grade 3) of the use of an antineoplastic agent – an inducer, prescribing drugs that reduce intestinal motility (loperamide) while excluding the infectious nature of diarrhea, intravenous methylprednisolone (for example, diarrhea caused by monoclinal antibodies in the absence of suspicion of potential bowel perforation). In cases where drug-induced diarrhea lasts more than 48 hours, or a patient reports symptoms of dehydration, or a fever occurs, urgent hospitalization is necessary.

The objective of this review is to analyze scientific literature data on the prevalence, pathophysiological mechanisms and risk factors for the development of diarrhea associated with the intake of anticancer drugs, as well as its prevention and treatment.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):5-18
pages 5-18 views

Current possibilities of predicting the development of pre-diabetes and type 2 diabetes mellitus

Petrankov K.V., Salukhov V.V., Pugachev M.I., Dobrovolskaya L.M., Stepanova T.V., Izilyaeva E.A., Shustov S.B.


Type 2 diabetes mellitus is a serious chronic disease that poses a serious public health problem since this pathology has a significant impact on health due to the high risk of occurrence and development of severe complications, which directly affects the socio-economic well-being of the population. The presented article analyzes the most significant links in the pathogenesis of type 2 diabetes mellitus, which makes it possible to determine the risk factors for its occurrence and development. The influence of obesity on disorders of carbohydrate metabolism, as well as other associated metabolic conditions, such as atherosclerosis, hypertension, dyslipidemia, has been emphasized. Anthropometric parameters and various indices are presented, allowing them to be assessed in relation to metabolic changes. The review summarizes the most convincing biochemical markers that have prognostic value in relation to the development of pre-diabetes and type 2 diabetes mellitus. The article pays special attention to the analysis and evidence base of the existing scales for assessing the risk of developing pre-diabetes and type 2 diabetes mellitus, including the first domestic calculator based on the DIARISK questionnaire. In addition, the article presents statistical data on the higher incidence of metabolic syndrome in people professionally associated with high psychoemotional load. However, the methods for assessing the risk of pre-diabetes and T2DM do not reflect the contribution of this factor to the development of carbohydrate metabolism disorders.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):31-42
pages 31-42 views

Diagnosis and prognosis of inflammatory bowel diseases: modern view

Bakulin I.G., Rasmagina I.A., Skalinskaya M.I.


About 5% of the population suffer from chronic diarrhea. Intestinal infections are the most common cause of diarrheal syndrome. However, if they are excluded, it is necessary to check for other possible reasons: vascular, oncological, rheumatic, drug-induced, radiation diseases and other gastroenterological pathology except from inflammatory bowel diseases.

When predicting and detrcting new predictors of unfavorable outcomes and progression of inflammatory bowel diseases, special attention has been recently paid to serological markers and genetic research, which have not yet entered clinical practice due to their high cost.

Inflammatory bowel diseases is a diagnosis of exclusion, which is made after a comprehensive assessment of clinical, laboratory, endoscopic, and morphological data. In case of the development of complications, it needs to investigate new available prognostic markers of inflammatory bowel diseases course.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):19-30
pages 19-30 views

Original research

Coexistent rheumatoid arthritis and hyperuricemia: clinical and immunological features

Mazurov V.I., Gaydukova I.Z., Fonturenko A.Y., Bashkinov R.A., Petrova M.S., Inamova O.V.


BACKGROUND: Currently, the negative role of asymptomatic hyperuricemia (HU) in the development and progression of cardiovascular pathology, metabolic disorders and chronic kidney disease is generally recognized. There is not much data in the literature on the effect of HU on the course of rheumatoid arthritis (RA), therefore, the study of the relationship of HU with clinical, radiological and immunological features of RA seems relevant.

AIM: To study the relationship between HU with the clinical, radiological and immunological features of RA.

MATERIALS AND METHODS: The data of 262 patients with RA and HU and 262 with RA without HU (comparison group) included in the city register from January 2000 to April 2020 have been analyzed. The information included demographic features (gender, age), diagnosis, presence and duration of HU, duration of observation, disease activity, laboratory, immunological, radiological and functional parameters, therapy of the underlying disease. HU was understood as a recorded ≥1-fold increase in the level of uric acid (UA) in the blood serum >360 mmol/l. The study has been approved by the local ethics committee.

RESULTS: The data of 524 patients with rheumatoid arthritis for the period from January 2000 to April 2020 have been analyzed. The study included 440 women and 84 men. The average age of the patients was 60.0 ± 13.6 y. The patients with HU have been divided into two subgroups: the first – with the level of UA less than 500 mmol/l, the second — with the level of UA more than 500 mmol/l. The number of males was significantly higher among the patients with high HU than among the patients with low HU and the comparison group. Every third patient had significant structural changes in the joints (radiological stage III-IV) and 98% of the patients had moderate and pronounced functional limitations (functional class 2-3). The patients with HU were older, had more follow-up visits, were observed for a longer period of time, had a lower frequency of radiological progression, a greater number of painful and swollen joints, less often and at a smaller dose had methotrexate and more often sulfasalazine in comparison with the patients without HU (p < 0.05).

CONCLUSIONS: 1) Thus, we can emphasize the negative impact of hyperuricemia on the course of rheumatoid arthritis: if it is present, there are direct (more PJ, SJ) and indirect signs of a more severe course (longer duration of observation and the number of visits). 2) Immunosuppressive therapy is associated with the absence of differences with the generally recognized markers of disease activity (ESR, CRP, DAS28), the immunological profile (RF, ACCP) and the ambiguous relationship with radiological progression and functional insufficiency of the joints, as well as unreliable relationship with a higher frequency of bone density reduction.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):43-52
pages 43-52 views

Estimating possibility of applying the modified cumulative illness rating scale (CIRS-Obs) for predicting postpartum infections and antimicrobial resistance

Korobkov N.A., Bakulina N.V., Repina M.A.


BACKGROUND: In obstetrics, there are no systems or scales for assessing somatic burden, predicting and choosing empirical antibiotic therapy in postpartum (postoperative) pyoinflammatory complications.

AIM: The given research aims to assess the reliability and validity of the Cumulative Illness Rating Scale for Obstetrics (CIRS-Obs), which has been firstly modified for obstetric patients. The study is based on the inclusion of additional variables that may be used as highly informative predictors of the development of infectious complications resistant to antibiotics following caesarean section to assess the prognosis.

MATERIALS AND METHODS: A retrospective study of 406 clinical records of obstetric patients suffering endometritis following caesarean section and admitted to the Gynecology department of the Mariinskaya Municipal Hospital has been carried out during the period from September 2008 to September 2020. Multivariate regression analysis allowed to establish a number of indicators characterized by a high predictive value in relation to the unfavorable course of postpartum infections and the isolation of multidrug-resistant pathogens in patients with aggravated somatic status. The most significant factors have been included in the variant of the cumulative comorbidity index (CIRS-Obs), which was firstly modified by the authors for obstetric patients.

RESULTS: The most significant predictors associated with a high risk of isolating resistant and multidrug-resistant pathogens in the examined patients suffering endometritis include CIRS score ≥4 points, an emergency caesarean section in combination with a prolonged labor and a period without amniotic fluid, antibiotic therapy in the third trimester of pregnancy, as well as previous hospitalizations during pregnancy/invasive procedures or operations.

CONCLUSIONS: The CIRS-Obs scale modified for obstetric patients by including highly informative predictors and developed to assess the risk of isolating resistant and multi-resistant pathogens in obstetric patients suffering endometritis following cesarean section in terms of a patient’s somatic status, antibiotic therapy, the category of urgency and conditions of the operation allows to increase the reliability of the prognosis to make efficient therapeutic decisions.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):53-62
pages 53-62 views

The role of the International classification of functioning in the complex rehabilitation of cardiac patients

Stolov S.V., Makarova O.V.


BACKGROUND: A new format for assessing impaired functions, disabilities and health in accordance with the international classification (ICF), which is necessary at all stages of rehabilitation, is considered of great importance in the practice of an interdisciplinary rehabilitation team. However, in practice, the use of the ICF is very limited due to a number of organizational reasons.

AIM: To raise awareness among specialists of different fields involved in the rehabilitation of a disabled person, about the main provisions of the ICF; discuss the gradation of rehabilitation potential developed by the authors in cardiac patients.

MATERIALS AND METHODS: An analysis of referrals to the medical and social expertise bureau (form 088 / U) of patients with cardiovascular diseases has been carried out with the allocation of groups of low and high rehabilitation potential.

RESULTS: An analysis of the main provisions of the ICF regulating the section of cardiovascular diseases is presented. This classification is the “gold standard” for assessing the quality of life and medical services provided, substantiating the need, volume and composition of individual rehabilitation measures for a disabled person. The ways of using the principles laid down by the ICF in clinical practice for evaluating the results of complex rehabilitation of patients with cardiac pathology are discussed. The main provisions of the ICF, influencing the quality of rehabilitation measures in patients with cardiological profile, are highlighted. A list of diseases / conditions has been developed and proposed for use, which involves various levels of rehabilitation.

CONCLUSIONS: The authors have developed and proposed for discussion the gradation of the rehabilitation potential of patients with cardiovascular diseases, as well as discussed the general provisions of the international classification of functioning, simplifying and facilitating the use of ICF in practical work, taking into account the standards of examination, treatment and rehabilitation for cardiac patients in accordance with the standards of examination, treatment and rehabilitation of cardiac patients approved in the Russian Federation.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):63-68
pages 63-68 views

Disruption of endothelial glycocalyx in patients with rheumatoid arthritis

Shimanski D.A., Nesterovich I.I., Inamova O.V., Trophimov V.I., Galkina O.V., Levykina E.N., Vlasov T.D.


BACKGROUND: Endothelial glycocalyx has an important role in the regulation of endothelial functioning. It is the first to be damaged during the development of autoimmune inflammatory diseases. Thinning of endothelial glycocalyx leads to a violation of the barrier function of blood vessels, the development and maintenance of the inflammatory process. In this context, using endothelial glycocalyx assessment for diagnostic and monitoring of diseases is considered of great interest.

AIM: To establish the relationship between endothelial glycocalyx thickness with activity, serological profile and risk factors for an unfavorable course of rheumatoid arthritis.

MATERIALS AND METHODS: The study included 76 patients from 18 to 65 years of both sexes with rheumatoid arthritis. The perfusion boundary region of endothelial glycocalyx determined using a dark-field microscope has been used as the main indicator for assessing the state of endothelial glycocalyx.

RESULTS: The obtained results have demonstrated a decrease in the initial endothelial glycocalyx thickness in females in the presence of risk factors for an unfavorable course of rheumatoid arthritis. At the same time, no relationship with the serological profile and endothelial glycocalyx thickness has been found. An inverse correlation between endothelial glycocalyx thickness and syndecan-1 level and erythrocyte sedimentation rate has been found. This confirms the fact that endothelial glycocalyxes are involved in the inflammatory process in rheumatoid arthritis. Endothelial glycocalyx assessment using dark-field microscopy made it possible to predict the subsequent appointment of pulse therapy with methylprednisolone in the hospital. On re-examination, endothelial glycocalyx thinning has been observed in the presence of unfavorable risk factors for the course of rheumatoid arthritis, in negative to anti-cyclic citrullinated peptide antibodies patients, or in the absence of response to treatment.

CONCLUSIONS: The use of dark-field microscopy is unique in its capabilities for intravital and non-invasive assessment of endothelial glycocalyx thickness. It provides important fundamental information deepening knowledge in the pathological physiology of disease. From a clinical point of view, it allows to consider a decrease in endothelial glycocalyx thickness as an additional prognostically unfavorable marker in rheumatoid arthritis.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):69-74
pages 69-74 views

Dynamics of clinical manifestations of irritable bowel syndrome against the background of cytoprotector rebamipide intake: intermediate results of the SOKRAT program

Simanenkov V.I., Bakulina N.V., Nekrasova A.S., Elokhina E.A., Topalova Y.G.


BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract, the detection rate of which in the general population is 9-23%, in the Russian Federation – 8.3-19%. IBS is the cause of chronic pain which accompanies patients throughout their life, significantly reducing its quality and disrupting social adaptation. Insufficient effectiveness of modern methods of treating IBS dictates the need to search for new drugs, the pharmacological action of which is aimed at the pathogenetic mechanisms of IBS formation. Currently, more and more attention in the development of IBS is paid to the syndrome of increased epithelial permeability, in connection with which it is promising to include the universal cytoprotector rebamipide in the complex therapy of patients with IBS.

AIM: To evaluate the effect of rebamipide on the course of irritable bowel syndrome.

MATERIALS AND METHODS: This article presents the intermediate results of the SOCRAT study, which has assessed the effect of rebamipide on the course of IBS. For this purpose, 40 patients with IBS have been examined and subsequently randomized into two groups comparable in gender, age and type of IBS. The patients of the main group (n = 21) received cytoprotector rebamipide in addition to standard antispasmodic therapy, and the patients of the comparison group (n = 19) received cytoprotector bismuth tripotassium dicitrate. Patients’ gastroenterological complaints have been assessed before and after treatment using GSRS, 7x7, IBS-QOL questionnaires and a visual analogue scale.

RESULTS: According to the study findings, the well-being of the patients has improved in the both study groups. However, more significant positive dynamics has been observed in the main group, as evidenced by a significant decrease in the frequency and severity of abdominal pain and symptoms caused by constipation, which, in turn, led to an increase in the quality of life of the studied patients.

CONCLUSIONS: Thus, protective therapy of epithelium with rebamipide has not only a symptom-reducing effect, but also a positive effect on the course of IBS.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):75-82
pages 75-82 views

Case report

Formation of necrotizing vasculitis in the patient with diffuse B-cell large cell lymphoma on immune checkpoint inhibitor (PD-1) therapy

Mazurov V.I., Melnikov E.S., Pavlyuchenko E.S., Dyakonova M.N.


INTRODUCTION: Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis and clinical outcomes for patients with malignancies in many types of cancer. Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and PD-L1/2, thereby preventing inhibition of T-cells, which contributes to the antitumor response. The use of ICT can lead to autoimmune aggression and the development of adverse events. Most of these are eliminated on their own after ICT therapy and steroid treatment have been discontinued.

CLINICAL CASE DESCRIPTION: A 73-year-old patient with recurrent large B-cell lymphoma, on the background of R-CHOP, R-CHOP-mini, R-GDOx therapy incomplete clinical effect and frequent relapses have been registered. On immunohistochemistry, PD-L1 was positive in 90 % of the tumor cells. A decision has been made to administer the checkpoint inhibitor (PD-1) nivolumab, which developed a necrotizing vasculitis after three injections.

CONCLUSION: On temporary withdrawal of the drug and administration of prednisolone at a dose of 1 mg/kg/day, the skin has recovered completely. When the PD-1 inhibitor was reapplied, there was no recurrence of autoimmune aggression. The treatment has been continued in the full way.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):83-90
pages 83-90 views

Systemic transtiretin amyloidosis in the elderly patient with recurrent pleural effusions

Boldueva S.A., Evdokimov D.S., Shvets N.S., Shahbazyan A.V., Kalinina E.Y., Mitrofanova L.B.


Systemic amyloidosis is a group of diseases associated with extracellular deposition of fibrillar proteins, which leads to a loss of normal organ structure and function. Transthyretin amyloidosis occurs with the deposition of amyloid, consisting of transthyretin transport protein, and can be a genetic or degenerative disease of senility (acquired from the deposition of wild-type transthyretin).

The article describes the clinical case of transthyretine amyloidosis in elderly patient, manifested by recurrent pleural effusions and biventricular heart failure demonstrating the complexity of timely diagnosis of wild-type transthyretin amyloidosis.

HERALD of North-Western State Medical University named after I.I. Mechnikov. 2021;13(3):91-98
pages 91-98 views

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