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Kuban Scientific Medical Bulletin

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Vol 29, No 3 (2022)
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ORIGINAL ARTICLES. CLINICAL MEDICINE

14-29 364
Abstract

Background. The epidemiology of ulcerative colitis in the Russian Federation is typified by late diagnosis and the predominance of severe complications entailing high mortality.
Objectives. A comparison of the diagnostic value of laboratory methods for assessing ulcerative colitis severity.
Methods. A total of 178 ulcerative colitis patients were divided into 4 cohorts by the presence and severity of attack; a control cohort included 40 healthy volunteers. Besides standard tests, a cytokine profile was determined in all patients: IL-1 IL-2, IL-4, IL-6, IL-10, TNF-α, IL-17; faecal inflammation marker concentrations — lactoferrin (LF), calprotectin (CalP), neopterin (NP); optical anisotropy (OA) of neutrophilic granulocyte nuclei; clinical activity index (CAI); Mayo scores. A single-factor analysis of variance was performed to compare the diagnostic value of laboratory tests, with a Mayo score taken as the factor reflecting ulcerative colitis attack severity. Differences were assumed statistically significant at p < 0.05.
Results. The patients suffering from ulcerative colitis exhibited statistically significant Mayo score correlations with IL-6 (r = 0.598, p = 0.001), IL-17 (r = 0.587, p = 0.005), TNF-α (r = 0.701, p = 0.001), CalP (r = 0.881, p = 0.001), LF (r = 0.799, p = 0.001), NP (r = 0.791, p = 0.001) and OA (r = –0.877, p = 0.001). Faecal inflammatory biomarkers varied in the range from 73.4 (NP) to 95.3% (CalP) of total variance. Serum markers varied from 75.2 (IL-6) to 88.1% (IL-17) of total variance. As of all markers, the highest diagnostic value was observed for CalP (95.3% of total variance), while the lowest — for NP (73.4% of total variance). In the analysis of variance, the cut-off values for serum markers in predicting endoscopically active disease (>1 Mayo score) comprised: IL-6 = 10.3 pg/mL; IL-17 = 18.5 pg/mL; TNF-α = 10.9 pg/mL. The analogous values for faecal markers were: CalP = 112.0 μg/g; LF = 80.9 μg/g; NP = 92.8 μg/g. Neutrophilic granulocytes optical anisotropy comprised 94.5% of total variance, which compares with CalP by diagnostic power.
Conclusion. A high diagnostic power has been demonstrated for faecal inflammatory markers (calprotectin, neopterin, lactoferrin), cytokines (IL-6, IL-17, TNF-α) and neutrophilic granulocytes optical anisotropy in detecting the attack relapse and severity.

30-45 340
Abstract

Background. Despite a wide range of studies, no consensus has been reached on the relative weight of ultrasound parameters for assessing local haemodynamically significant carotid deformations.
Objectives. To estimate a diagnostic value for an additional multiparametric ultrasound parameter for local haemodynamically significant carotid deformations.
Methods. In the first phase, 388 patients underwent an outpatient multiparametric ultrasound examination of the carotid arteries. The study involved patients of the age of 18 and older with a primary referral for carotid ultrasound by a resident physician, neurologist or cardiologist in order to rule out a carotid pathology. As a supplement to the main haemodynamic significance assessment parameters, we introduced an additional metric — the deformity coefficient – in order to diagnose carotid abnormalities. Based on the first phase results, two cohorts were selected. Cohort 1 (control) consisted of patients with no abnormalities in multiparametric carotid ultrasound. Cohort 2 consisted of patients with isolated unilateral internal carotid artery deformities at no haemodynamically significant stenosis of common and internal carotid arteries in multiparametric carotid ultrasound. In the second phase, the patients underwent transcranial duplex sonography of the middle cerebral arteries, in order to detect regional haemodynamically significant internal carotid artery deformities.
Results. Mathematical modelling of abnormal arteries produced the empirical upper deformity coefficient thresholds to distinguish acute angulation. This value is >1.41 for C-shaped and >1.34 — for S-shaped curves.
Subsequent statistical analysis revealed a clear positive correlation between angulation and the deformity coefficient at a p < 0.01 significance level. More acute angulation corresponds to higher coefficient values.
The Spearman correlation between the deformity coefficient and blood flow asymmetry values for middle cerebral artery was 0.89. This defines a significant positive correlation (higher deformity coefficient corresponds to higher blood flow asymmetry) at a p < 0.01 significance level.
Conclusion. The deformity coefficient is an additional ultrasound parameter for assessing local haemodynamically significant carotid abnormalities.

46-61 484
Abstract

Background. Premature termination of pregnancy, including miscarriage, remains among the critical problems in modern obstetrics and gynaecology practices. In the context of early gestational failure and the notion that 80% of early miscarriages are triggered by genetic reset — some natural filter — an analysis of current knowledge of the genetic aspects of missed abortion (MA) appears relevant.
Objectives. A study of the haplotype frequencies for VDR rs10735810, MTHFR rs1801131, MTHFR rs1801133, MTR rs1805087, MTRR rs1801394 and VEGFA rs3025039 polymorphic loci and their association with vitamin D deficiency in women with missed abortion.
Methods. A total of 178 women aged 18 to 41 years were examined. The main cohort consisted of MA patients (n = 101) who were divided between cohort I (n = 58; patients with primary MA) and cohort II (n = 43; patients with recurrent MA). The control cohort (n = 77) consisted of women with a successful pregnancy (Z34.0) entailing a term and live birth. Genotyping of polymorphic loci VDR rs10735810, MTHFR rs1801131, MTHFR rs1801133, MTR rs1805087, MTRR rs1801394 and VEGFA rs3025039 was performed in 177 patients. Total serum 25(OH) D (n = 99) was determined by mass spectrometry. Statistical analysis was carried out using the Statistica v. 10 data analysis software (StatSoft, Russia; TIBCO, USA).
Results. No differences were revealed for the frequencies of studied haplotypes between MA women and those who gave birth to healthy full-term newborns (p >0.1). No association was found between first-trimester MA and the presence of polymorphic loci variants (p >0.1). The GG haplotype of gene VDR is even less frequent in recurrent MA patients than in control (14.0% vs. 23.7%; OR = 2.29; 95% CI: 0.738–7.075). The GG haplotype of gene MTR has a 2-fold higher frequency in primary MA patients compared to control, albeit at no statistical significance (8.6 vs. 4.0%). Haplotype TT of the gene VEGF polymorphism occurs even less frequently in primary MA patients than in control (3.5 vs. 7.9%, respectively). Patients with first-trimester MA exhibited an association between vitamin D deficiency and the frequency of polymorphic variants VDR rs10735810 (p = 0.0304) and MTHFR rs1801133 (p = 0.0180). The other studied genes did not reveal such an association.
Conclusion. The study demonstrates a pathogenetic association of polymorphic variants VDR rs10735810 and MTHFR rs1801133 with missed abortion and vitamin D deficiency.

ORIGINAL ARTICLES. MEDICAL AND BIOLOGICAL SCIENCES

62-75 314
Abstract

Background. Personalised medicine is an avenue to create technologies for individual prognosis of the disease onset and development. The identification of individual gene haplotypes is prerequisite to detecting predispositions to multifactorial diseases. The level of serum 8-oxoguanine is an indicator of genotoxic stress underlying many pathologies.
Objectives. A study of associations of mmp12 gene’s polymorphic variant rs652438 and the nature of genome oxidative damage in bronchial asthma.
Methods. Genotyping of polymorphic variant rs652438 of gene mmp12 was performed using TaqMan-probe real-time PCR assays. The gene variant association with disease was assessed by odds ratio. The degree of DNA oxidative damage was estimated by 8-oxoguanine serum concentrations determined in monoclonal antibody-based enzyme immunoassays. The StatPro software package with StatTools (Palisade Corporation, USA) was used for statistical data processing.
Results. The haplotype and allele frequencies were established for polymorphic locus rs652438 of the mmp12 gene in the control and bronchial asthma cohorts. Heterozygotes were shown to differ significantly; the estimate was 2.3-fold higher in the control vs. bronchial asthma (BA) cohort (p < 0.05). The AA and GG haplotype frequencies did not differ significantly. The minor allele G odds ratio (OR = 0.362, CI 95% 0.134–0.975) suggests its protective effect. This may be associated with a lowering activity of the encoded macrophage metalloelastase enzyme, which results in a poorer extracellular matrix destruction in the bronchial tree. The baseline 8-oxoG levels in the control and BA samples were 6.4 and 9.4 ng/mL, respectively (U = 25, Ucut-off = 23; p >0.05). An in vitro electromagnetic exposure of varying frequency leads to a significant oxidative genomic damage in both cohorts and an earlier reparative depletion in bronchial asthma vs. control.
Conclusion. A protective effect of minor allele G against pathology has been demonstrated. Adaptations to oxidative genomic stress in bronchial asthma manifest by an impaired resistance to in vitro high-intensity electromagnetic exposures.

76-88 3724
Abstract

Background. The study relevance is substantiated by the growing numbers of road vehicles and cervical spine traumas occurring among all spinal injuries. Currently, there is no common vision of the cervical trauma pathogenesis, diagnostic algorithm or treatment, which stipulates difficulties in the forensic evaluation of soft tissue injuries of the neck, especially combined with the head or spine traumas around neck, as well as certain diseases.
Objectives. A study of the incidence of cervical spine distortion injuries and their clinical and forensic assessment for severity to human health.
Methods. A retrospective selective single-stage trial and analysis of 32 forensic medical reports on road accident and physical injury administrative cases in 2017 (single year) have been conducted. Normally distributed data are presented as mean (M), standard deviation (SD) and percent shares. The significance of inter-share variation was estimated with Student’s t-test.
Results. Cervical spine distortion injuries more frequently associated with traumas to drivers than passengers inside the salon (81.2%), especially in passenger vehicles, with front-seat travellers inflicted most often (60.0%). Cases of independent pathology were very rare. The most common were combinations with soft tissue injuries, combined blunt trauma to the head, torso and limbs, with craniocerebral or maxillofacial trauma. Cervical osteochondrosis was revealed in 18% cases. Primary diagnosis predominantly grounded on complaints and history (67%), with only 12% cases using a comprehensive neurological examination or instrumental methods. The severity was assessed in the context of concomitant injuries. Acute and moderate severity had equal rates of 6.2%, light severity — 37.5%, no damage — 9.3%. Non-qualified remained 39.8% cases due to a lack of full clinical and instrumental examination (66.7%) or the victim’s failure to appear (13.3%); 20% cases were expert-reported as uncertain for trauma circumstances and mechanism.
Conclusion. Further research and systematisation of the data accumulated are necessary. The following clinical and forensic evaluation, as well as statistical analyses will facilitate common diagnostic and severity assessment algorithms to develop for mechanical soft tissue and ligament injuries of the cervical spine.

CLINICAL CASE

89-102 1811
Abstract

Background. The past decade has witnessed the advent of direct oral anticoagulants (DOACs) into clinical practice for the prevention and treatment of venous thromboembolism, as well as stroke prevention in atrial fibrillation (AF) patients. A serious complication of anticoagulant treatment is bleeding. Randomised controlled trials have shown that the risk of already developed bleeding does not reduce upon a DOAC replacement. In such cases, the bleeding cause diagnosis and elimination are recommended instead of a anticoagulant replacement. An anticoagulant treatment can only be resumed once the elimination is completed.
Clinical Case Description. Patient K., 81 yo, was emergently admitted to a cardiology ward of the Rostov Regional Clinical Hospital with a clinical picture of bilateral pulmonary embolism of small arterial branches confirmed in multislice computed angiopulmonography. Apart from venous embolism, persistent atrial fibrillation was detected as an additional indication for DOAC treatment. A CHA2DS2-VASc risk of thrombosis was 6, HAS-BLED risk of bleeding — 2. Glomerular filtration rate at bleeding was 90 mL/min/1.73 m2. The patient was prescribed rivaroxaban at 20 mg daily. Past 2 years and 3 months, rivaroxaban has been withdrawn due to bleeding developing from scrotal veins. An urologist examination revealed a bilateral spermatic cord veins dilation. A Valsalva test revealed persistent retrograde veinous blood flow. Varicocele detected on both sides.
The patient underwent venous occlusion of left internal spermatic vein following an Ivanissevich procedure. The cause of bleeding was eliminated. The patient resumed rivaroxaban 1 week since the operation.
Conclusion. The case describes a rare cause of bleeding that has been established at a continued new DOAC therapy.

TOPICAL ARTICLE

103-120 482
Abstract

Background. The relevance of the problem is supported by the lack of effective secondary prevention measures against human papillomavirus (HPV)-associated cervical intraepithelial neoplasia (CIN) and cervical cancer. The only currently verified treatment for lower genital neoplasia is destructive therapy, with the recurrence rate of viral infection remaining quite high even after such interventions. The preventive role of HPV vaccine at pre-existing cervical lesions is actively debated worldwide, but the evidence remains scattered and contradictory. The present study surveys the scientific publications available that evaluate the efficacy of human papillomavirus vaccination as a secondary prevention measure against related cervical pathology.
Objectives. An evidence survey on the efficacy of adjuvant vaccination against human papillomavirus in patients undergoing destructive therapy for cervical intraepithelial neoplasia.
Methods. We have conducted a 10 year-depth review of scientific literature on the adjuvant human papillomavirus (HPV) vaccination efficacy for reducing the recurrence risk of precancerous cervical neoplasia. The results are presented in form of the difference of mean or pooled 95% confidence-interval odds ratios (OR; 95% CI). Statistical analyses were conducted with Review Manager v. 5.4 (The Cochrane Collaboration, 2020).
Results. Thirteen Russian- and English-language studies were selected for final analysis. A total of 21,702 cervical dysplasia patients were included: 5,941 (27.4%) received a perioperative HPV vaccine, while 15,761 (72.6%) only had surgical treatment. Recurrences of CIN I (mild cervical intraepithelial neoplasia; OR 0.45, 95% CI 0.27–0.73; p = 0.001) and CIN II (moderate cervical intraepithelial neoplasia; OR 0.33, 95% CI 0.20–0.52; p <0.0001) were lower in the vaccinated vs. unvaccinated cohort.
Conclusion. Adjuvant HPV vaccination associates with a lower risk of recurrence in cervical intraepithelial neoplasia. Further research is necessary to shed more light on the role of human papillomavirus vaccination as a secondary prevention measure against its associated lesions.

BRIEF COMMUNICATIONS

121-134 646
Abstract

Background. In every region of the Russian Federation, medical waste management importantly relies on both safe and cost-effective decontamination.
Objectives. The study aims to highlight the hygienic aspects of medical waste management in healthcare facilities of Krasnodar Krai and county-wide, as well as to prove the cost effectiveness of the physical decentralised decontamination/neutralisation method in a multi-specialty healthcare facility.
Methods. A retrospective analysis of medical waste management over Krasnodar Krai and at a multi-specialty hospital has been conducted for period 2016–2018; cost effectiveness was calculated for the decentralised (physical) method of medical waste decontamination. Statistical analyses were performed with Statistica 10.
Results. A high proportion of medical waste has been established for both Krasnodar Krai and country-wide. The cost effectiveness of the physical decentralised waste decontamination method has been demonstrated. The estimates with Ochapovsky Regional Clinical Hospital No. 1 Research Institute showed that a per-kilo deactivation cost for class B (epidemiological hazard) waste by a decentralised (physical) method is more effective amounting to average 38.42 ± 4.48 vs. 191.20 ± 20.46 (p < 0.01) for specialised commercial services of medical waste collection, transportation and neutralisation; the use of a reliable validated physical method warrants the staff epidemiological safety.
Conclusion. The cost effectiveness of the physical decentralised method of medical waste decontamination/neutralisation has been demonstrated with a multi-specialty hospital. Better legal regulation and inter-department coordination of medical waste management will upgrade the disposal solutions to ensure compliance with epidemiological and environmental safety.



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ISSN 1608-6228 (Print)
ISSN 2541-9544 (Online)