Vol 51, No 3 (2023)

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The relationship between urine steroid metabolome and the course of adrenocortical cancer

Velikanova L.I., Vorokhobina N.V., Shafigullina Z.R., Kalugina V.V., Malevanaya E.V., Strelnikova E.G., Buinova M.O., Lisitsyn A.A., Kushlinskii N.E.


Background: Adrenocortical cancer (ACC) is a rare aggressive and rapidly metastatic disease. Early diagnosis of the disease and its metastatic stage are important for the choice of treatment strategy. Evaluation of urine steroid profiles (USP) by gas chromatography-mass spectrometry (GC-MS) is a highly sensitive and specific biomarker instrument that allows for differentiation between benign and malignant tumor and obvious prospects for the diagnosis in patients with adrenal incidentalomas. In our previous study we have found no difference in urine excretion of tetrahydro-11-deoxycortisole (THS), 5-ene-pregnenes and 3α,16,20-pregnenetriol/3β,16,20-pregnenetriol ratio (3α,16,20-dP3/3β,16,20-dP3) in patients with metastatic ACC in early postoperative period, compared to pre-operative parameters. We did not account for the disease stage and primary tumor size in that study in ACC patients.

Aim: To identify specific characteristics of urine steroid metabolome by GC-MS in ACC I–IV stages patients before surgery in order to detect early signs of metastases and the relationship between adrenal steroidogenesis abnormalities and disease stages.

Materials and methods: We performed a retrospective analysis of the data from the study of USP in 59 ACC stage I-IV patients with L. M. Weiss score ≥ 3, according to pathological examination of the surgical samples. The Cushing syndrome was diagnosed by immunochemistry assay in 28 (47.6%) of ACC patients. Tumor staging was done according to ENSAT based on the results of imaging and postoperative histological reports. ENSAT I was diagnosed in 8 patients, ENSAT II in 26, ENSAT III in 14, ENSAT IV in 11 ACC patients. The control group included 28 healthy donors. USP was assessed by GC-MS before surgery with a gas chromatography-mass-spectrometer Shimadzu GCMS-ТQ8050.

Results: The first variant of urinary steroid metabolome abnormalities with increased excretion of dehydroepiandrosterone (DHEA) and THS was found in 10 (90.9%) of ENSAT IV ACC patients and in 20 (50%) of ENSAT II + III patients. The fourth USP variant was characterized by no difference in androgen and THS urinary excretion from that in healthy individuals and was found in ACC ENSAT I patients. Only in ACC ENSAT I patients, there was an increase of pregnanediol (P2) urinary excretion and of the P2/pregnanetriol (P3) ratio, compared to those in healthy donors. ROC-analysis demonstrated that ТНS > 867 mcg/24 hours, 3β,16,20-dP3 > 300 mcg/24 hours and 3α,16,20-dP3/3β,16,20-dP3 < 1.6 cut-offs had a sensitivity and specificity of 100% for preoperative identification of ENSAT IV ACC patients before surgery and for early diagnosis of ACC metastases. There were positive correlations between 16-oxo-androstenediol, THS, and progestogens, as well as a negative correlation between 3α,16,20-dP3/3β,16,20-dP3 ratio and the disease stage.

Conclusion: Urinary excretion of THS, DHEA and its metabolites, P2, 5-ene-pregnenes, and 3α,16,20-dP3/3β,16,20-dP3 ratio determined by GC-MS are important biochemical markers of ACC stages and can be used as ACC metastases prognostic markers.

Almanac of Clinical Medicine. 2023;51(3):143-153
pages 143-153 views

Comparative assessment of computed tomography and magnetic resonance imaging in the identification of the middle ear cholesteatoma

Stepanova E.A., Garov E.V.


Background: Chronic suppurative otitis media amounts up to 22.4% among all ear, nose and throat disorders. Its complication, a middle ear cholesteatoma, is one of the most frequent causes of patients' referral to an otologist. The literature on the preferential diagnostic method for the cholesteatoma is contradictory, despite that its main treatment approach is surgery. Therefore, it is important to identify the most valid diagnostic method, which would allow for the planning of the most effective surgical treatment.

Aim: To compare sensitivity and specificity of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of cholesteatoma, to assess the possibility of quantitative values of MRI diffusion limitation in cholesteatoma.

Materials and methods: From 2015 to 2021, we examined 542 out- and in-patients (849 imagings of temporal bones) with chronic suppurative otitis media. The analysis of CT and MRI sensitivity and specificity included the data from 289 patient examinations, both with newly diagnosed cholesteatoma and having at least one past surgery and had their diagnosis verified intraoperatively and histologically. We analyzed the measured MRI diffusion coefficients from newly diagnosed and relapsed cholesteatoma. The MRI signal values were calculated for 266 masses from 238 patients.

Results: MRI sensitivity for the diagnosis of cholesteatoma was 95.2%, specificity 81.2%. CT sensitivity and specificity for the diagnosis of cholesteatoma were 60.1 и 44.7%, respectively. There were no differences in the measured MRI diffusion coefficients between the relapsed and newly diagnosed cholesteatomas. The comparison of cholesteatoma signals with those from artifacts showed the overlapping in their mean values; therefore, it is impossible to rely only on the value of the diffusion coefficient.

Conclusion: In the diagnosis of cholesteatomas, MRI is significantly more sensitive and specific than CT. No significant differences in MRI semiotics and the degree of MRI diffusion limitation at NON-EPI DWI (b1000) have been found for the cholesteatomas that had never been operated, and the relapsing cholesteatomas.

Almanac of Clinical Medicine. 2023;51(3):154-162
pages 154-162 views

Vincristine polyneuropathy in children with acute lymphoblastic leukemia: the association with the hereditary rs924607 polymorphism in the CEP72 gene

Koryakina O.V., Kovtun O.P., Tsaur G.A., Tsyganko E.V., Fechina L.G., Bazarnyi V.V.


Background: Vincristine polyneuropathy is a major neurotoxic complication of treatment for acute lymphoblastic leukemia in children. A close relationship between genetic variants in candidate genes associated with the vincristine neurotoxicity in various ethnic groups has been proposed. Therefore, identification of the genetic risk factors underlying the predisposition to vincristine polyneuropathy could allow the development of effective tools for preventive diagnostics aimed at identifying a high-risk group among patients treated with vincristine for a personalized approach to their chemotherapy.

Aim: To study an association between the rs924607 polymorphism of the CEP72 gene and vincristine polyneuropathy in children with acute lymphoblastic leukemia.

Materials and methods: This single center cohort study enrolled 199 children aged 3 to 17 years with newly diagnosed acute lymphoblastic leukemia, who received ALL-MB 2015 chemotherapy regimen. All patients were genotyped for the single nucleotide variant rs924607 in the CEP72 gene by real-time polymerase chain reaction and subsequent allelic discrimination. A comparative analysis of the incidence and clinical signs of vincristine polyneuropathy depending on the carrier of the genetic polymorphism was performed.

Results: The incidence of vincristine polyneuropathy in the study pediatric group was 81.0% (n = 161); mostly these were patients with NCI-STCAE grade 2 severity. The rs924607 single nucleotide variant in the CEP72 gene was significantly associated with the neurotoxic complication, with 19.1% (n = 38) of the patients were homozygous for the minor allele (rs924607 genotype TT) and 46.2% (n = 92) had the ST genotype. Among the carriers of at least one rs924607 risk allele (T), the odds ratio for vincristine polyneuropathy was 2.91 (95% confidence interval 1.41–5.99, p = 0.004). No significant association between the genetic variant assessed and clinical signs of vincristine-induced polyneuropathy was found.

Conclusion: The single nucleotide rs924607 polymorphism of the CEP72 gen can be a putative pharmacogenetic marker for vincristine polyneuropathy.

Almanac of Clinical Medicine. 2023;51(3):163-170
pages 163-170 views

The informative value of noninvasive tools for assessment of liver fibrosis in chronic hepatitis B patients under antiviral treatment with nucleoside and nucleotide analogues

Nguyen T.H., Ilchenko L.Y., Melnikova L.I., Kyuregyan K.K., Gordeychuk I.V.


Background: Antiviral therapy (AVT) with nucleoside and nucleotide analogues (NAs) for chronic hepatitis B (CHB) is aimed at prevention of the development and progression of fibrosis, liver cirrhosis, and hepatocellular carcinoma. Therefore, monitoring of changes in liver fibrosis over time with noninvasive tests is a necessary prerequisite for the assessment of treatment efficacy. However, there are very few studies on changes of transient elastometry (TE) over time, the calculated indices APRI and FIB-4 under AVT in patients with CHB.

Aim: To assess changes in noninvasive tests (TE, APRI, FIB-4) over time and to identify factors influencing the fibrosis severity in CHB patients treated with NAs.

Materials and methods: This retrospective study was performed in 42 CHB patients, in whom noninvasive methods (TE, APRI and FIB-4) were used before and during NA-based AVT. The patients were divided into two groups: those with a significant reduction in liver density (SRLD, at least by 25% from their baseline TE) and those without a significant reduction (< 25%).

Results: Virological response was achieved in 38/42 patients after NA-based AVT (mean duration, 21 months). TE values decreased significantly in the patients with severe fibrosis/cirrhosis (F3/F4) (from 14.2 to 8.3 kPa, p = 0.001), with minimal/moderate fibrosis (F1/F2) (from 5.9 to 5.1 kPa, p = 0.009), and in HBeAg-negative patients (from 6.9 to 5.2 kPa, p < 0.001). The F3/F4, F1/F2, HBeAg-positive and HBeAg-negative patients demonstrated a significant reduction in APRI and FIB-4 indices (all p < 0.05). Higher baseline TE values were independently associated with SRLD (odds ratio 1.324; 95% confidence interval (CI) 1.029–1.702; p = 0.029). Baseline TE, APRI, and FIB-4 values positively correlated with their values on treatment (all p < 0.05). The AUROC values of APRI and FIB-4 reduction as SRLD predictors were 0.632 (95% CI 0.457–0.807; p = 0.160) and 0.578 (95% CI 0.391–0.764; p = 0.408), respectively.

Conclusion: NA-based AVT promoted the regression of fibrosis in CHB patients. A high baseline TE value was identified as an independent SRLD predictor. At the same time, despite moderate positive correlations between TE, APRI and FIB-4 parameters, the calculated indexes APRI and FIB-4 cannot be used to predict SRLD. The decrease in liver tissue density by at least 25% correlated only with TE parameters, which makes it possible to recommend TE for monitoring liver fibrosis in CHB patients treated with NA.

Almanac of Clinical Medicine. 2023;51(3):171-179
pages 171-179 views

Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial

Talybov R.S., Trofimova T.N., Mochalov V.V., Shvetsov I.V., Spasennikov V.V.


Background: The main purpose of surgery for glioblastoma is to ensure the maximally possible cytoreduction. Computed tomography perfusion imaging has non-invasive tools for assessment of tumor blood flow and allows for visualization of the tumor borders and its most malignant zones.

Aim: To evaluate the efficacy of intraoperative computed tomography perfusion navigation (ICTPN) during surgery for high grade gliomas.

Materials and methods: This prospective non-randomized study included 142 patients (76 men and 66 women) with morphologically verified diagnosis of glioblastoma or diffuse astrocytoma grade 4 (World Health Organization 2021 criteria), who had surgery from 2016 to 2022. The ICTPN-based procedures were performed in 94 patients, with 55 with gross total and 39 with subtotal tumor resection. The control group included 48 patients with non-ICTPN-based surgical procedures. All patients were treated with standard adjuvant chemoradiation therapy. The efficacy of surgery was assessed every 3 months. The study endpoint was any tumor progression. The duration of the follow-up was 15 months. Baseline and contrast-enhanced preoperative imaging and postoperative follow-up assessments were performed with a 3T magnetic resonance imaging scanner (General Electric Discovery W750). ICTPN was done with a 32 slice computed tomography scanner (Toshiba Aquilion LB).

Results: In the totally resected ICTPN group, the mean duration of the relapse-free period was 13.05 months; the relapse-free survival at 6 and 12 months was 92 and 55%, respectively (p < 0.001). These results were significantly better than those in the subtotally resected ICTPN patients (8.98 months, 66 and 9%, respectively; log rank test for Kaplan-Meier curves, p < 0.001) and in non-ICTPN patients (5.81 months, 23 and 0%, respectively, log rank test, p < 0.001).

Conclusion: ICTPN enables a more objective assessment of the tumor borders and the extent of its resection, as well as relapse-free survival benefits for the patients.

Almanac of Clinical Medicine. 2023;51(3):


The potential of electromyography, diagnostic transcranial magnetic stimulation, and multiparametric magnetic resonance imaging in the combinatory assessment of facial nerve disorders: a literature review and clinical case series

Marchenko N.V., Novokshonov D.Y., Irikova M.A., Shevchenko E.Y., Dubitsky D.L., Voitenkov V.B., Alkhazishvili A.V., Skripchenko E.Y.


Facial neuropathy (FN) is a complex multicausal problem that, with a seemingly obvious clinical picture, might be challenging to diagnose. Up to 5% of FN cases could be caused by neoplastic or otogenic processes, necessitating an interdisciplinary approach to its treatment by various specialties and in some cases a surgical intervention. In addition, in the early stages of FN, it is difficult to predict its outcomes. Therefore, beyond usual neurological exam and widely used electromyography (EMG), other additional diagnostic tools are used to ensure extended diagnosis, including cancer awareness.

In this paper we have analyzed the principles, role and value of computed tomography, magnetic resonance imaging (MRI), diagnostic transcranial magnetic stimulation combined with EMG, and ultrasound assessment with a high-frequency linear transducer in acute FN. We present our own clinical cases of pediatric patients with FN, who were assessed with EMG and multiparametric MRI including diffusion tensor imaging. These cases illustrate both the abnormalities found in the typical course of Bell's palsy, as well as the abnormalities in neoplasm-associated FN that clinically fully mimic the Bell's palsy. Based on the world experience in multiparametric MRI, including the use of extended protocols in the Pediatric Research and Clinical Center for Infectious Diseases, in case of suspected FN, the most important are high-resolution structural submillimeter sequences based on the gradient echo (SSFP) and diffusion tensor imaging (DTI). Measurement and assessment of fractional anisotropy at the motor nuclei of the facial nerves in the pons look promising for further research. The paper is the first to describe a modified combination diagnostic approach to Bell's palsy with the use of diagnostic transcranial magnetic stimulation with round coil, supramaximal stimulation with identification of the motor evoked response threshold (minimal inducer power to register a reproducible evoked motor response of 50-100 mV in amplitude) in the occipito-parietal area of the ipsilateral muscle.

Almanac of Clinical Medicine. 2023;51(3):180-191
pages 180-191 views

CASQ2: clinical and genetic insights into catecholaminergic polymorphic ventricular tachycardia across three families

Kulbachinskaya E.K., Bereznitskaya V.V.


Catecholaminergic polymorphic ventricular tachycardia is a primary channelopathy with a high mortality rate if left untreated. In 3 to 5% of catecholaminergic polymorphic ventricular tachycardia patients, mutations in the CASQ2 gene, either in a homozygous or compound heterozygous form, have been identified. In this article, we present a clinical case series of patients from three unrelated families with mutations in the CASQ2 gene, including three novel mutations (p.Leu167Pro, p.Asp325GlyfsTer7, and p.Glu259Ter). All our patients with homozygous or compound heterozygous CASQ2 gene mutations experienced a severe disease course, with early manifestations and resistance to specific anti-arrhythmic treatment, including beta-blockers. They exhibited a wide range of heart rhythm abnormalities, both ventricular and supraventricular, and had a high risk of sudden cardiac death. In all cases, ventricular heart arrhythmias persisted despite regular treatment with specific anti-arrhythmic agents, unless selective left-sided sympathectomy had been performed. The management of this patient group emphasized an individualized approach, combining medical and surgical treatment methods tailored to each patient's unique needs and condition.

Almanac of Clinical Medicine. 2023;51(3):192-199
pages 192-199 views

The diagnostic potential of cone beam computed tomography for cervical spine injuries in children: a review of two reports

Erenkov I.O., Voronin V.A.


Compared to multiaxial computed tomography, the cone beam computed tomography has its benefits in terms of higher resolution imaging, including the construction of a 3D image, and in terms of several fold lower radiation exposure. The duration of scanning of less than 1 minute and the possibility to place a patient in the sitting position allow for the use of this method in various fields of stomatology, maxillofacial surgery, as well as in traumatology for the assessment of limb injuries.

The paper presents our experience with the cone beam computed tomography as a single method for radiation diagnostics in children with cervical spine injuries. The first case is an example of the use of this method for primary diagnosis and subsequent follow-up of the restoration of the atlantoaxial position in a 9-year old child with rotatory subluxation of the atlant. To clarify the type of the injury, we combined and compared the axial planes of the 1st and 2nd cervical vertebrae. In the second case, we explored the possibility to assess the restoration of the bone structure and mutual position of the upper cervical vertebrae with the images obtained by cone beam computed tomography in a 9-year old girl with the Down's syndrome, who had been operated due to a cervical spine injury.

The analysis of the cone beam computed tomography images from the first clinical case delineates the prospects of the method in the diagnostics of the atlant rotation subluxation in school-age children. Evaluation of the images obtained during the examination of the second clinical case has identified some disadvantages of the cone beam computed tomography, namely: 1) there is no way to control the fixed patient position, 2) limitations of the software to suppress artifacts arising from the metal construction, which leads to advanced image blurring and flatness, significantly hindering the identification of abnormalities.

Almanac of Clinical Medicine. 2023;51(3):200-205
pages 200-205 views

Retraction notices

Retraction of the article “Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial”


The editors (publisher) have retracted the article by R.S. Talybov, T.N. Trofimova, V.V. Mochalov, I.V. Shvetsov, V. V. Spasennikov. Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial. Almanac of Clinical Medicine. 2023;51. doi: 10.18786/2072-0505-2023-51-012. Received 14 April 2023; revised 15 May 2023; accepted 5 June 2023; published online 15 June 2023.

The retraction reason: research ethics violation by the authors in terms of submission of misinformation on the ethics approval for the study and on the signing of the informed consent by the patients for participation in the study. The authors have been informed on the decision.

Almanac of Clinical Medicine. 2023;51(3):

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