Vol 51, No 1 (2023)
REVIEW ARTICLE
Bile acid dysmetabolism in inflammatory bowel diseases
Abstract
Aim: To summarize the state-of-the-art data on the molecular mechanisms of bile acid (BA) synthesis and absorption, their impaired absorption and receptor-dependent signaling, as well as on the effects of the gut microbiota on BA metabolism in inflammatory bowel diseases (IBD).
Key messages: BA malabsorption is one of the relevant mechanisms in the development of diarrhea in IBD. It may occur due to various disorders of the ileum, such as terminal ileitis, ileocolitis or ileocecal resection in Crohn's disease and ileoanal reservoir in ulcerative colitis. Molecular mechanisms of BA malabsorption in IBD are related to a defect in the BA uptake by the apical sodium dependent bile acid transporter (ASBT), as well as to a decrease in the expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR), whose activation by glucocorticoids results in an increase in the BA reabsorption in the ileum and a decrease in hologenic diarrhea. The metabolic profile of luminal BA in IBD is characterized by an increased content of conjugated and 3-OH-sulfated BA and reduced levels of secondary BA. The decrease in the relative abundance of the Lachnospiraceae and Oscillospiraceae spp. in IBD patients leads to a decrease in the efficiency of microbial biotransformation of BA. Changes in the BA metabolic profile in IBD affect the gut microbiota, and impaired interaction with the FXR, PXR, G protein-coupled bile acid receptor (GPBAR1), retinoid-related orphan receptors (RORs) and vitamin D receptor (VDR) results in a pro-inflammatory response and increased intestinal permeability, bacterial translocation, and IBD progression. BA metabolism in IBD-associated primary sclerosing cholangitis (PSC-IBD) is characterized by a significant decrease in the luminal BA pool, and the microbiota composition is remarkable for an increase in the relative abundance of Fusobacterium and Ruminococcus spp., and a decrease in Veillonella, Dorea, Blautia, Lachnospira and Roseburia.
Conclusion: Disordered synergistic interplay of BA with intestinal microbiota results in disruption of the ligand-receptor interaction and BA metabolic transformation, which contributes to the activation of the immune system, formation of a vicious circle of chronic inflammation and IBD progression. Further studies into mutual influence of the gut microbiota, BA metabolism and receptor signaling may promote the development of new methods for the diagnosis and treatment of IBD.
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Stroke and peripheral vestibulopathy as a part of acute vestibular syndrome
Abstract
The scope of the review is the problem of differential diagnosis between stroke and peripheral vestibulopathy in patients with acute vestibular vertigo. A vertebrobasilar stroke manifesting with the isolated vertigo has been previously recognized to be extremely rare, and the symptoms have been related to the involvement of peripheral parts of the vestibular analyzer. Recently there has been growing evidence that the isolated vertigo syndrome is commonly related to the central involvement of the vestibular analyzer. The author presents published clinical cases of acute cerebrovascular accident with a single symptom of acute vestibular vertigo. It can be also a symptom of a hemispheric stroke due to an injury of vestibular pathways connecting the vestibular nuclei with the parietal cortex. These observations extend the understanding of the common classic pathognomonic picture of central vestibular vertigo, which implies that its development is related exclusively to the brain matter lesion in vestibulobasilar stroke.
Current clinical rating scales and tests (NIHSS, FAST) used for the diagnosis of an acute stroke, are frequently not sensitive to the vertebrobasilar stroke, and neuroimaging, including brain magnetic resonance imaging at DWI mode, may give false negative results. The most informative differential diagnostic method in acute vestibular syndrome is an otoneurological assessment including identification of nystagmus characteristics and head turn impulse test, for the assessment of vestibuloocular reflex and at bed tests (for example, tests included into the HINTS PLUS protocol). In this regard, it is important that neurology specialists in regional vascular centers and departments for acute cerebrovascular care should master the otoneurological assessment skills.
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ARTICLES
Galectin-3 and matrix metalloproteinases 2 and 9 in peripheral blood of gastric cancer patients
Abstract
Background: High incidence of gastric cancer (GC), its aggressive clinical course, rapid tumor dissemination, low sensitivity to chemotherapy and lack of reliable laboratory diagnostic criteria urgently require a search for the most informative markers associated with key biologic properties of the tumors.
Aim: Comparative analysis of galectin-3, matrix metalloproteinase (MMP)-2, and MMP-9 levels in peripheral blood of GC patients and healthy donors, assessment of association of these markers with clinical morphological characteristics of the disease, and prognosis of overall and relapse-free survival.
Materials and methods: Sixty (60) primary treatment-naïve GC patients (38 men, 22 women) aged 29 to 81 years and 90 healthy donors compatible with their age and sex were included into the study. Galectin-3 was measured in EDTA plasma, MMP-2 and MMP-9 in serum with standard direct enzyme immunoassay kits "Human MMP-2 (total)", "Human MMP-9 (total)", "Human Galectin-3" (R&D Systems, USA).
Results: Plasma galectin-3 concentration in the GC patients was significantly higher than in the healthy controls (median 12.9 and 10.6 ng/ml, respectively; p < 0.0001). No difference in serum MMP-9 levels between GC patients and control subjects were found, while MMP-2 level in the control group was significantly higher, than in the GC patients (p = 0.039). No association between galectin-3, MMP-2, and MMP-9 blood levels in the GC patients could be identified. In contrast to GC patients, there was a positive correlation of plasma galectin-3 with age in the control group (rs = 0.51, p < 0.005). No associations between the biomarkers levels in blood and clinical and morphological characteristics of GC were established, except MMP-9 being higher at Т4а invasion depth as compared to the earlier Т2 level. Marked differences in the overall survival depending on plasma galectin-3 levels were found, with the cut-off level of 12.9 ng/ml: the 5-year overall survival in the patients with low galectin-3 was better, than in those with its higher level (50 and 43%, respectively; however, the difference was non-significant, р > 0.1). Both overall and relapse-free survival of the GC patients was higher in those with low (< 212 ng/ml) serum MMP-2: the 5-year overall survival in this group comprised 60% versus 23% in the patients with higher MMP-2 (p = 0.018). The difference in relapse-free survival was non-significant. Serum MMP-9 levels had no significant impact on the survival of GC patients.
Conclusion: The ambiguous data on the clinical role of galectin-3, MMP-2, MMP-9 in GC obtained in this study indicate the necessity of further investigation of their possible utility for the diagnostics and prognosis of treatment results.
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The results of surgery for giant aneurysms of the middle cerebral arteries: a retrospective study
Abstract
Background: Surgical treatment of middle cerebral artery (MCA) giant aneurysms is a challenging task. The information on its current principles is rather limited, with the publications based on isolated case reports and small series.
Aim: To identify the types of procedures and evaluate the results of surgery in patients with giant MCA aneurysms.
Materials and methods: We retrospectively analyzed the data on 55 patients who had undergone surgery for MCA giant aneurysms in the Burdenko Neurosurgery Center from 2010 to 2021. Thereafter 52 patients were followed up for 6 to 120 months (for 53.1 ± 33.7 months on average).
Results: The giant MCA aneurysms were located at the M1 segment bifurcation in 33 (60%) patients, within the M1 segment, in 11 (20%), M2 in 7 (12.7%), and M3 and M4 in 4 (7.3%) patients. There were 32 (58.2%) saccular and 23 (41.8%) fusiform aneurysms. Surgical interventions for MCA giant aneurysms included their neck clipping (50.9%, n = 28), clipping with formation of the arterial lumen (3.6%, n = 2), bypass procedures (34.5%, n = 19), wrapping (3.6%, n = 2), and endovascular procedures (7.3%, n = 4). Perioperative worsening of the neurologic status (The Modified Rankin Scale, mRS) was observed in 50.9% (n = 28) of the patients, and the death rate was 1.8% (n = 1). The complete closure of giant aneurysms was achieved in 78.2% (n = 43) of the cases. The long-term outcome was favorable in 76.9% of the patients (40 from 52 available for the follow up).
Conclusion: Microsurgical clipping and bypass types of surgery were the most common surgical procedures for the treatment of MCA giant aneurysms. These procedures are technically complex and are associated with a relatively high number of complications. The main directions of future studies could be in the search for new and more precise diagnostic assessment of the collateral circulation in the cortical MCA branches, improvement of the algorithm for the bypass selection, as well as an investigation of the long-term results of endovascular and combined treatments. A thorough long-term postoperative patient follow-up and the possibility of high quality control angiography are of major importance.
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Evaluation of the upper extremity motor skills with a computer kinetic system in multiple sclerosis patients
Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating neurodegenerative disorder with multiple lesions in the central nervous system. Motor abnormalities are considered to be a major cause of permanent occupational, social and daily disability of MS patients. However, due to serious limitations of existing methods for assessment of upper limb functioning, evaluation of coordinator and motor abnormalities in the upper extremities in clinical practice is difficult.
Aim: To evaluate the efficacy of a computer kinetic method in the diagnosis of fine motor abnormalities of upper limbs in MS patients at early stage of the disease, when motor abnormalities in the upper limbs are not yet obvious.
Materials and methods: The main study group included 42 patients with confirmed MS, who consented for testing and met the inclusion criteria (among them, absence of obvious motor and coordinator abnormalities in the arms). The mean age of the patients was 36 [29; 44] years. The control group included 31 healthy subjects with a mean age of 28 [21; 37] years. All the patients were assessed with an original computer kinetic system, including a two-minute test, when the patient had to follow a moving object on the screen with a computer mouse. Every test series resulted in 13 final characteristics.
Results: The test of the dominant hand showed that compared to the control group, the MS patients without clinical motor abnormalities in the upper extremities spend 20% more time to move to the aim object (p < 0.001), have a 18% lower output motor performance (p < 0.001), make by 54% more recurrent returns to the aim object (p = 0.012), by 7% more crosses of the ideal trajectory of moving to the aim (p = 0.036), by 32% more deviations from the ideal trajectory of moving along the x axis and by 52% more along the y axis (p < 0.001 for both comparisons), as well as they have a 12% lower mean rate of the movements during the computer test (p < 0.001) and by 12% more rate picks (p = 0.003).
Conclusion: Patients with confirmed MS, low degree of disability and absence of any clinically confirmed motor abnormalities in the upper limbs do have subclinical signs of motor abnormalities in the arms that can be identified by computer kinetic system.
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Osteopontin in patients with chronic obstructive pulmonary disease and coronary heart disease
Abstract
Background: Osteopontin is a protein expressed by various cell types, such as endothelial and epithelial cells, osteoclasts, hepatocytes, smooth muscle cells, activated macrophages, and T-cells. Cardiomyocytes, heart fibroblasts, endothelial cells of coronary arteries express osteopontin in response to hypoxia, inflammation, toxic factors, mechanical strain, and other stimuli.
Aim: To study osteopontin levels in patients with chronic obstructive pulmonary disease (COPD) depending on concomitant ischemic heart disease (IHD), to identify an association between osteopontin levels with severity of COPD and functional lung test parameters.
Materials and methods: This open-label, prospective, non-randomized comparative study with parallel groups included 99 patients with COPD grades A–D by GOLD, with 49 of them having confirmed comorbid stable IHD. Serum osteopontin levels were measured by immunoenzyme assay (Human Osteopontin Platinum ELISA; Bender MedSystems, Austria). The data is given as medians and quartiles (Me [Q1; Q3]). In all patients we performed functional lung tests with bronchodilation, a 6-minute walking test, BODE index assessment, as well as CAT and mMRC questionnaires were used.
Results: In the patients with COPD and IHD, the osteopontin levels were higher than in the patients with COPD without IHD (85.55 [46.86; 110.91] vs 55.43 [20.76; 89.64] ng/mL, respectively; p = 0.027). Osteopontin levels in the patients with all COPD grades and IHD were higher than in those without IHD, but the difference was significant only in GOLD grade B patients (91.28 [73.04; 110.91] vs 37.81 [22.54; 82.95] ng/mL, respectively, р = 0.028) and GOLD grade D patients (80.79 [34.65; 111.11] vs 37.46 [13.32; 109.5] ng/mL, respectively, р = 0.027).
Conclusion: A significant increase of osteopontin levels in comorbid patients with COPD and stable IHD found in this study has not been previously known. It is necessary to perform further studies to identify a threshold level of osteopontin predictive of the risk of COPD exacerbations or cardiovascular events. This would help to improve medical treatment of COPD patients, as well as to identify the risk groups.
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Evaluation of the neutrophil-leukocyte index in patients with cardiac disorders and new coronavirus infection
Abstract
Background: The neutrophil-leukocyte index (NLI) is an independent predictor of an unfavorable outcome in stable ischemic heart disease, as well as of mortality in patients with acute coronary syndromes and uncontrolled heart failure. A number of studies have shown the informative value of NLI for the prediction of severe course of COVID-19. NLI variability in COVID-19 with comorbid baseline physical diseases and cardiovascular disorders in particular, has not been studied.
Aim: To evaluate the clinical value of NLI in hospitalized patients with COVID-19 depending on their concomitant cardiac disorders.
Materials and methods: In this retrospective quantitative study we have analyzed the data from medical files of the patients with the diagnosis of new coronavirus infection confirmed by polymerase chain reaction, treated in a specialized in-patient department of infectious diseases in 2020 to 2022. Previously diagnosed cardiac disorders were defined as any past history of these disorders. The results of instrumental and laboratory work-up were assessed before treatment.
Results: The analysis included 226 patients with median age of 50.0 (Q1–Q3: 42.0–63.0) years, with 81.4% (n = 184) of them being men. Ninety four (41.6%) patients had no previously diagnosed cardiovascular disorders. Arterial hypertension by the time of admittance was present in 132 (58.4%), ischemic heart disease, in 77 (34.1%), atherosclerotic and/or post-infarct cardiosclerosis, in 82 (36.3%), and chronic heart failure, in 77 (34.1%) of the patients.
In the total study group (n = 226) the median NLI was 2.6 (1.57–4.47). The larger was the volume of the lung involvement (assessed by computed tomography at admittance), the higher was NLI (p = 0.009, Kruskal-Wallis test). There was an association between the NLI value and the degree of respiratory failure (p < 0.001, Kruskal-Wallis test). Median NLI in the patients with cardiac disorders (irrespective of their nosology) was significantly higher than that in the patients without any history of cardiovascular problems: 3.30 (2.09–5.42) versus 1.95 (1.42–3.62) (p < 0.001, Mann-Whitney U-test). We found significant difference in the NLI values for each type of cardiac disorders, compared to that in the patients without history of cardiovascular disorders, including for the patients with arterial hypertension (p < 0.001, Kruskal-Wallis test), ischemic heart disease (p < 0.001, Mann-Whitney U-test), atherosclerotic cardiosclerosis (p = 0.001, Mann-Whitney U-test), and chronic heart failure (p = 0.040, Kruskal-Wallis test).
Conclusion: We have confirmed the contribution of cardiovascular disorders to the course of COVID-19 and the clinical value of NLI as a convenient laboratory marker of the severity of infectious disease.
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