EDITORIAL
Background. The population prevalence of alcohol abuse-associated drug-related diseases bears high social impact. This indicator holds special value both as a potential indirect estimator of the quality of life, availability and efficiency of drug addiction treatment, a well as parameter for qualitative prognostic models of social and economic development. The burden of alcohol-associated drug diseases is typically ambiguous in prevalence estimation, both across Russian Federation and worldwide.
Objectives. A study of the alcohol abuse-associated drug-related morbidity prevalence in Krasnodar Krai for period 2000–2020.
Methods. A retrospective descriptive study included legal-paper data of the “Information on Drug-Related Disorders” federal statistics survey (Form 11) of Krasnodar Krai, years 2000-2020, describing the re-registration rate of alcohol use-associated drug disorders. The inclusion criterion was an established drug-related disease among all age cohorts. The main study indicators were regional prevalence values of alcoholic psychosis, alcohol dependence syndrome and harmful alcohol use relative to gender, area and age.
Results. Prevalence trends in alcohol use-related drug pathology were more favourable in Krasnodar Krai over Southern Federal District and country-wide. The decline rate among males was significantly higher (22.1-fold) vs. the female population (3.0-fold). The prevalence of alcohol use-related drug pathology remained higher in urban vs. rural areas, with higher rural vs. urban decline rates. Over the entire study period, the 40–59 years-age population was leading by the incidence of overall alcohol use-related drug pathology and, separately, of alcoholic psychosis and alcohol dependence syndrome. Highest harmful alcohol use values were registered for 20–39-year population.
Conclusion. The revealed dynamics of legal-registered alcoholic drug pathology prevalence has a multifactorial origin. The changes are conditioned by improvement in the narcological aid institutional regulation within the state guarantee programme, federal and regional preventive measures, current progress in drug therapy, regional demography, as well as underreporting of alcohol-associated drug diseases due to a missing strict vertical statistic registration at the level of any-type medical institutions.
ORIGINAL ARTICLES. CLINICAL MEDICINE
Background. Nonrational nutrition is among main risk factors of chronic noncommunicable diseases (CNCDs) that can be contained via adopting and motivating population to a healthy diet by clarifying territorial, gender and age-specific eating behaviours.
Objectives. A study of urban gender and age-specific eating behaviours associated with universal and metabolic CNCD risk factors.
Methods. An observational cohort study has been conducted with 1,317 urban residents (657 men and 660 women) aged 18–74 years at Kuban State Medical University, Ministry of Health of the Russian Federation, using anonymous surveys on food preferences, tobacco and alcohol consumption, physical activity (PA), as well as physical examination, anthropometry, electrocardiography (ECG) and biochemical blood tests.
Results. Urban residents revealed low-physical activity (PA) (88%), overweight and obesity (33%), high tobacco (65%) and alcohol use (39%) in men, high metabolic risk by waist/hip circumference (33.7%) and significant polymorbidity in hypertension (3 to 8 diseases per person). The urban dietary pattern can be described “intermediate” by the co-presence of rational and nonrational ingredients in diet. Rational ingredients prevailed in women and elderly people. Elevated total cholesterol, low-density lipoproteins, triglycerides, gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid, urea, creatinine and ultra-sensitive C-reactive protein in blood were associated with foods intake like chips and breadsticks, potatoes, sweet drinks, confectionery and borscht.
Conclusion. Adopting measures to rational nutrition in population may comprise a clear declaration of dysmetabolic nature of specific foods, eating behaviour monitoring and motivated self-control of body mass index and waist girth beyond medical check-ups.
Background. The likelihood of intraoperative critical incidents depends largely on reflex control of the cardiorespiratory system that is often susceptible to chronic pathology. The reflex suppression may link to the depth of anaesthesia, making the latter monitoring particularly important at higher hypotension risks and their patient predisposition.
Objectives. A study of the effect of bispectral index anaesthesia monitoring on critical incidents (CIs) rate in high-risk abdominal surgery patients.
Methods. A randomised controlled trial enrolled 80 high-risk and 80 low-risk patients. Each cohort randomly allocated patients between subcohorts (by 40 people): 1 — anaesthesia rendered to maintain a 40–60 bispectral index (treatment cohort), 2 — by clinical values and anaesthetic level control in exhaled gas (control cohort), intraoperative control of anaesthetic requirement, bispectral index and critical incidents.
Results. A critical incidents rate analysis in high-risk patients showed a lower rate in the bispectral index anaesthesia control cohort. Total 127 critical incidents were registered in 53 patients. The analysis revealed fewer CIs for objective sedation depth monitoring, 45% patients of treatment cohort vs. 87.5% in control. Significantly fewer (by half) patients exhibited hypotension in the treatment cohort, with lower (4-fold) rates of arrhythmia, bradycardia and general respiratory CIs. Anaesthetic doses and bispectral indices at anaesthesia stages were significantly lower in the treatment cohort as well.
Conclusion. Objective anaesthesia depth monitoring in high-risk patients reduces the rates of haemodynamic incidents during anaesthesia maintenance and respiratory incidents at arousal due to prevention of excessive anaesthetic depth.
Background. Secondary postoperative diffuse peritonitis (SPDP) associates with a high incidence of abdominal sepsis and 35–92% mortality rate. An optimal surgical doctrine in this complication in lacking to date.
Objectives. An efficacy assessment of vacuum-assisted laparostomy (VAL) with staged lavage relative to relaparotomy on demand (RD) in SPDP patients.
Methods. Patient enrolment and analyses were conducted within period 01.11.2017-31.12.2020, totalling for 141 SPDP patients, 77 (54.6%) males and 64 (45.4%) females aged 64.5 (5972.7) years. Cohort I patients (n = 52) had post-abdominal-lavage VAL using Suprasorb® SNP (SNP-1 and SNP-2) equipment and consumables (Lohmann & Rauscher GmbH, Austria). Staged lavage was performed 48-72 h apart. Cohort II (n = 78) had a standard RD technique. Cohort III (n = 11) treatment included RD-to-VAL transition. The endpoint was the inpatient treatment outcome, a favourable completion or death. The additional estimated criteria were complications rate and severity (in ACCORDION-modified Clavien-Dindo classification), sepsis rate, C-reactive protein level, abdominal index dynamics, patient’s intensive-care and total-hospital lengths of stay.
Results. Cohort I included 157 staged-lavage VALs, cohort II — 107 RDs, cohort III — 49 operations. The mortality rate was 3/52 (5.8%), 24/78 (30.8%) and 7/11 (63.6%) in cohorts I, II and III (respectively, p < 0.001). No difference was observed in the length of hospital stay, with a shorter intensive care stay after final abdominal closure in cohort I. Clavien — Dindo grade 3a complications were observed for 25.0% of cohort I, 60.3 and 45.5% — of cohorts II and III (respectively, p < 0.01); grade 3b complications were 0 (0%), 24.4 and 100% in cohorts I, II and III (respectively, p < 0.001; all 11 patients were reoperated). Multiple organ failure (grade 4b) was reported in 5.8, 30.8 and 63.6% of cohorts I, II and III (respectively, p < 0.001). By end of treatment, sepsis had resolved in 9/11 (81.8%) patients in cohort I, 5/24 (20.8%) and 1/6 (16.7%) — in cohorts II and III (respectively, p = 0.002).
Conclusion. Programmed staged-lavage VAL is an optimal surgical treatment tactics in SPDP. Relative to RD, VAL provides a more effective management of local and systemic abdominal sepsis, lower mortality, fewer and less sever complications, shorter intensive care stays after abdominal closure.
ORIGINAL ARTICLES. MEDICAL AND BIOLOGICAL SCIENCES
Background. Over the past decades, scientific community is motivated on finding new anti-inflammatory agents with a safe and high-effective profile to manage pathology.
Objectives. A study of the anti-inflammatory action of novel compounds, 1,4-dihydropyridine derivatives, in a classical formalin-induced paw oedema test in white rats.
Methods. Originally synthesised 1,4-dihydropyridine derivatives were preliminarily subjected to virtual screening using the SwissTargetPrediction toolkit. White laboratory rats (130 animals) were divided into a control (formalin oedema) and intact group, 4 comparison (meloxicam, sodium metamizole, sodium diclofenac and indomethacin) and 7 experiment groups by the number of 1,4-dihydropyridine derivatives studied. The samples anti-inflammatory efficacy was evaluated in acute formalin-induced paw oedema model simulated by right hind limb subplantar injection of 0.1 mL 2% formalin. The studied substances were administered intragastrically at 5 mg/kg 1.5 h prior to oedema induction. Oncometry was assessed quantitatively by limb circumference. Animals were managed in compliance with GOST 33044–2014 “Principles of Good Laboratory Practice” at all experiment steps. Experimental data were analysed statistically to describe quantitative variability with variance σ2, mean limb girth a and standard deviation σ. Data homogeneity and reliability were estimated by variation coefficient V and the Wilcoxon T(W) criterion.
Results. As the most anti-inflammatory effective, partially hydrogenated mar-040 pyridines (ethyl 4-({[5-cyano-6-{[2-(diphenylamino)-2-oxoethyl]thio}-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-yl]carbonyl}amino) benzoate) were shown 33-fold superior to indomethacin, 26-fold — to sodium diclofenac, 25-fold — to meloxicam and 30-fold — to sodium metamizole; mar-037 pyridines (ethyl 4-[({[3-cyano-5-({[4-(ethoxycarbonyl)phenyl]amino}carbonyl)-4-(2-furyl)-6-methyl-1,4-dihydropyridin-2-yl]thio}acetyl)amino] benzoate) — 17–23-fold superior vs. reference drugs. We also show that mаr-014 (ethyl 4-({[5-cyano-6-({2-[(3,5-dichlorophenyl) amino]-2-oxoethyl}thio)-4-(2-furyl)-2-methyl-1,4-dihydropyridin-3-yl]carbonyl}amino)benzoate) and mar033 (ethyl 2-[({[3-cyano-5-({[4-(ethoxycarbonyl)phenyl]amino}carbonyl)-4-(2-furyl)-6-methyl-1,4-dihydropyridin-2-yl]thio}acetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate) compounds are 2.7-fold more effective vs. reference drugs.
Conclusion. The synthesised 1,4-dihydropyridine compounds reveal high efficacy in experimental assays. Selected novel 1,4-dihydropyridine derivatives exhibit a marked anti-inflammatory activity and offer value in future preclinical trials.
CLINICAL CASE
Background. Porphyria unites genetic pathologies related to abnormal haem (an intermediate product of haemoglobin metabolism) synthesis and its toxic products accumulation in human body. Symptoms can vary, from photosensitivity, skin rashes and chronic abdominal pain towards partial or complete paralysis and acute psychosis. This metabolic disorder is diagnosed with molecular genetic and laboratory biosample tests. Drug therapy aims at reducing toxic metabolites concentration in patient’s blood.
Clinical Case Description. A 28-yo female patient had an acute atypical porphyria attack with a later onset of neurovisceral manifestations (acute abdominal pain, tachycardia) progressing post-drug-treatment into acute sensorimotor polyneuropathy with flaccid, predominantly proximal, hands-prevalent tetraparaesis. Biochemical urine tests at the National Research Center for Hematology (by 30.06.2020) revealed porphobilinogen 55.3 mg/L at norm <3. Vital indications required an urgent haem arginate pathogenetic therapy (Normosang) in a 4-day course of 3 mg/kg/day drop infusion. The recommended course was well tolerated. Drug therapy and rehabilitation entailed a positive dynamics of restoring limb muscle strength towards an almost easy getting-up from chair and bed, and skin lightening. The patient was discharged on day 20 with diagnosis: “Acute intermittent porphyria. Axonal-demyelinating sensorimotor polyneuropathy. Severe flaccid asymmetric predominantly proximal hands-prevalent tetraparaesis. Subacute course, stabilisation phase. Condition after one course of haem arginate pathogenetic therapy (Normosang) at 3 mg/kg/day”. A resident haematologist surveillance was recommended, with a routine referral for inpatient examination and treatment at the Department of Orphan Diseases of the National Research Center for Hematology, Ministry of Health of Russia.
Conclusion. Porphyria is relatively rarely diagnosed, about 12 cases per 100,000 people. The symptoms variety and nonspecificity conduce to a low detection rate, and untimely diagnoses can entail severe clinical manifestations, including lethal outcomes.
Background. Facial nerve injury, filler-induced compression or soft tissue infiltrations are among the neuropathic complications of aesthetic injection procedures. The prospects of ultrasound imaging in neuropathy diagnosis are understudied. National and foreign literature does not describe facial soft tissues ultrasound in patients with cosmetic injectable-induced clinical neuropathy.
Clinical Cases Description. Two clinical cases are presented of high resolution ultrasound (HRU)-empowered verification of injectable cosmetic procedures-induced neuropathy. Ultrasound imaging was proved necessary for differential neuropathic causes diagnosis via the clinical assessment of facial soft tissues, filler and thread depth, as well as topography relative to blood vessels and nerves. In the first case, threads were visualised at a 4.6 and 5.8 mm depth from epidermis, which can coincide in location with large facial nerve branches usually running along vessels in deeper subcutaneous fat. Vessels were not detected in immediate proximity to threads along the entire trajectory from implantation to fixation sites by colour Doppler imaging (CDI). The ultrasound pattern corresponded to dermal and soft tissue infiltration. In the second case, ultrasound was applied to differentially diagnose a iatrogenic cause of neuropathy, considering a 3-year-past history of filler injection at temporal muscle projection. A filler bolus was revealed adjacent to a vessel in subaponeurotic fat of right temporal region, with infiltrative signs of perifocal oedema around a piece of hyaluronic acid. Temporal soft tissue of the opposite facial half remained unchanged. According to HRU evidence, neuropathy developed due to nerve compression by facial soft tissue infiltrative distortions after thread implantation in the first case and by filler directly in the second. The HRU examination facilitated a correct diagnosis and choice of patient management.
Conclusion. Ultrasonography is indicated in patients with cosmetic procedures-induced neuropathy for differential diagnosis of complication causes and current therapy monitoring.
Background. Mucopolysaccharidosis type IVA (Morquio syndrome) is a rare genetic lysosomal storage disease. Due to rarity, the syndrome is typically diagnosed at a later stage of gross affections of musculoskeletal and central nervous systems, leading to disability and a markedly reduced quality of life. A replacement therapy is nowadays available with recombinant human N-acetylgalactosamine-6-sulfatase (elosulfase alfa) enzyme.
Clinical cases description. Two siblings, 10-yo male and 8-yo female, were admitted with complaints of growth retardation, deformity of the spine, thorax and joints, impaired hearing and visual acuity, poor tolerance to exercise. In the boy’s medical history, first manifestations appeared in the first year of life and progressed gradually; the patient was being observed as spondylodysplastic. Mental development was unaffected. The diagnosis was confirmed only by age of 7 at the National Medical Research Center for Children's Health Federal State Autonomous Institution of the Ministry of Health of the Russian Federation. Genotyping revealed two SNP mutations in gene GALNS (g.88909227C>A and g.88884454G>A in heterozygous state), and enzymatic assays — a severely reduced N-acetylgalactosamin-6-sulfatase activity. A routine elosulfase alfa replacement therapy has been received since 8-year age.
The younger sister had neonatal cardiomegaly; congenital carditis and cardiomyopathy not excluded. Musculoskeletal affections developed by age of 3–4 years. By age of 5 and simultaneously with brother, the same GALNS mutations and severely impaired N-acetylgalactosamine-6-sulfatase activity were detected. A replacement therapy has been routinely received since 6-year age. The therapy triggered positive dynamics of restoring activity and muscle strength in both children, as well as significantly abating the musculoskeletal affection progress.
Conclusion. The clinical cases of Morquio syndrome presented demonstrate its long-term and complex diagnosis. A replacement therapy is nowadays available, which warrants an earliest disease detection to halt progression and improve the patient’s life quality and expectancy.
ISSN 2541-9544 (Online)