Vol 52, No 4 (2024)
ARTICLES
Clinical significance of analysis of long non-coding RNA PSMB8-AS1, MBNL1-AS1, and OLMALINC expression by polymerase chain reaction in non-small cell lung cancer
Abstract
Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines.
Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance.
Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median).
Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms.
Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.
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Uterine layers hypervascularization in atypical placentation: the comparison of magnetic resonance imaging with vascular pathomorphology
Abstract
Rationale: One in five women worldwide delivers through cesarean section, which is associated to a high rate of placenta previa and abnormal placenta attachment to the uterine wall. The grade of placenta accreta spectrum (PAS) correlates with blood loss volume, which could be related to vascularization characteristics. Up to now, there have been no studies on the diagnostic value of magnetic resonance criteria for hypervascularization of the uterine wall and their correlation with an assumed grade of PAS according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Also, abnormal vessels location and their wall structure have not been studied with state-of-the-art pathomorphological methods.
Aim: To develop a classification for various types of the uterine wall hypervascularization depending on the depth of placental invasion assessed by magnetic resonance imaging (MRI).
Methods: We retrospectively analyzed medical files of 66 patients aged 18 to 45 years, who were assumed to have PAS based on their sonography results. To clarify the extent and localization of the placental invasion, all patients had MRI performed at 24 to 32 weeks of gestation. In all patients, the PAS grade was verified pathologically; in 30 of them (45,5%), a detailed pathological examination was additionally performed. The PAS grades were classified according to Morbidly Adherent Placenta Imaging Reporting and Data System (MAPI-RADS). The MRI data were correlated with the PAS (FIGO) grade estimated from intraoperative data and with intraoperative blood loss. At the final study step, the MRI data was correlated with abnormal pathomorphology, with the assessment of the degree of vascularization and the visual picture of abnormal uteroplacental vasculature.
Results: We have proposed a classification of MRI signs of hypervascularization in the lower uterine segment correlating with the depth of placenta accreta.
Type 1. Single small vessels in the myometrium, medium caliber arteries in the projection of the uterine serosa (normal variation for the 3rd trimester of gestation).
Type 2. Numerous small confluent vessels, mainly in the uteroplacental region, and retroplacental hematomas (typical for placenta accreta, or FIGO PAS 1).
Type 3. Intrauterine hypervascularization with a deficient myometrium thickness, predominantly vessels of the middle layer (typical for placenta increta, or FIGO PAS 2).
Type 4. Thinning of the lower uterine segment due to significant bulging of the placenta in the presence of curved anastomosing vessels of vast caliber over 4 mm (typical for placenta increta – FIGO PAS 2, as well as placenta percreta – FIGO PAS 3a).
Type 5. Hypervascularization outside the uterus, over its surface and in the parametrial tissues: at the border with the bladder, uterine isthmus, including signs of fibrosis and growing into the posterior bladder wall (typical for various grades of placenta percreta – FIGO PAS 3b, 3c).
Conclusion: The proposed classification of uterine wall hypervascularization in accordance with the grades of placenta accreta spectrum (FIGO PAS) could be useful for its practical implementation by radiologists.
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Efficacy of tablet glucocorticoids depending on their starting dose in patients with type 2 amiodarone-induced thyrotoxicosis: a prospective randomized study
Abstract
Background: Glucocorticoids are the first-line pharmacotherapy for amiodarone-induced destructive thyroiditis. Despite the availability of clinical guidelines, there is no unified approach to patient management (indications for prescription, starting dose, duration of therapy and withdrawal algorithm). The issues of dose-dependent effect of glucocorticoids, verification of factor of delayed treatment response, prediction of severity and duration of thyrotoxicosis remain unresolved.
Aim: To evaluate the efficacy of various regimens of tablet glucocorticoids in patients with type 2 amiodarone-induced thyrotoxicosis.
Methods: This was a prospective randomized open-label comparative controlled trial of the efficacy of two starting doses of prednisolone 30 mg (n = 22) and 60 (n = 22) mg daily. The study groups were comparable for gender (men to women ratio 2:1), age, anthropometric and main clinical and laboratory characteristics. After euthyroidism has been achieved, thyroid function was assessed twice at 1 and 2 months during the dose reduction and at 1, 3, 6, 9, and 12 months after prednisolone withdrawal. The follow up was 15 to 24 months. The efficacy of therapy was evaluated by the time to euthyroidism, thyrotoxicosis duration, rate of recurrent waves of destruction and relapses. We looked for predictors of delayed treatment response and severe and prolonged thyrotoxicosis.
Results: There were no significant differences in the time to euthyroidism (Mantel-Cox log rank test 0.859), duration of thyrotoxicosis (Mantel-Cox log rank test 0.813), rate of recurrent waves of destruction (0.721) and relapses (0.464). Within 30 days of therapy, remission was obtained in 11/22 (50.0%) patients in active control group (prednisolone 30 mg) and in 12/22 (54.5%) patients in the 60 mg group. Delayed response (> 60 days) was defined by recurrent waves of destruction (RR = 34.7, 95% CI: 3.7–321.8; R² = 0.430; p = 0.002). High risk of severe thyrotoxicosis was predicted by the age ≤ 54 years (AUC 0.749 ± 0.095, 95% CI: 0.562–0.936; p = 0.038; sensitivity 71.4%, specificity 62.2%). The duration of thyrotoxicosis was associated with body mass index (B = -7.4, R = 0.481, R² = 0.0231; p = 0.024) and cumulative amiodarone dose (B = 0.4, R = 0.472, R² = 0.223; p = 0.026). A combination of adverse events (hyperglycemia, infection, proximal myopathy, change in appearance, hematomas) and their severity were more frequent in the patients who had received the 60 mg prednisolone starting dose (p = 0.014).
Conclusion: Compared to lower doses, the use of high doses of glucocorticoids is associated with a greater severity of side effects and does not ensure any significant acceleration of thyrotoxicosis remission. The potential factors of unfavorable clinical course of type 2 amiodarone-induced thyrotoxicosis are age, body mass index, and cumulative dose of amiodarone.
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Development and validation of an image-based questionnaire ARTROVIS to identify risk factors for the articular syndrome and related conditions
Abstract
Background: The importance of timely diagnosis of rheumatic diseases is beyond any doubt. However, in the real practice the time from manifestation of the first symptoms to the assessment by a rheumatologist and treatment administration often exceeds the window of opportunity for disease control. At the moment, there has been no Russian-language questionnaire that would allow a primary care physician to suspect a rheumatic disease manifesting with an articular syndrome.
Aim: To develop, validate and test a questionnaire to identify risk factors for joint disorders and related conditions.
Methods: From November 2022 to April 2024, we performed the study on the image-based questionnaire on identification of the risk factors for joint syndromes and associated conditions (ARTROVIS), which we have developed for early detection of both joint syndromes, as well as comorbid conditions associated with elevated serum uric acid levels (hyperuricemia). The initial test version of the questionnaire was tested in a focus group of respondents (n = 20) who came for regular medical examination. Based on the results of this face validity assessment, we corrected the wording of 10 questionnaire items. At the second study step, we assessed the primary validity and reliability of the questionnaire in a group of 41 rheumatology patients. The third study step involved 828 respondents (408 men and 420 women, median age 19 [18,0; 20,0] years; 21% with joint syndromes), who came for routine medical examination. The reliability of the questionnaire, its face and discriminant validity, as well as sensitivity and specificity (the ROC analysis) were assessed from 827 questionnaires included in the final processing (one was excluded due to questionnaire completion defects).
Results: The self-report questionnaire for patients (ARTROVIS) has 24 items aimed at collecting social and demographic data, identifying risk factors for non-communicable diseases, assessing genetic aspects, identifying complaints from various organ systems, providing information on medical treatments taken by the patient (non-steroid anti-inflammatory agents, diuretics, antihypertensives, glucocorticosteroids, chemotherapy and radiation therapy), as well as an additional question for women on current pregnancy pathology. The questionnaire contains visual aids (colored photos) that facilitate the detection of clinical signs of autoimmune (psoriatic arthritis, Reynolds’s syndrome) and inflammatory rheumatic disease (gout), as well as the differential diagnosis of the joint syndrome. The assessment of face validity of the questionnaire showed the total number of missed answers of 3.42%; 62.85% of the respondents gave their full answers to all items. Good discriminant validity was demonstrated. The ROC analysis showed high correlation between the questionnaire score and the presence of a joint syndrome: the area under the curve was 0.884. The Cronbach’s alfa was 0.798, which is sufficient for a medical questionnaire.
Conclusion: We have performed the approbation and standardization of the questionnaire to identify risk factors for the joint syndrome and related comorbidities by assessing its validity and reliability. The ARTROVIS as a self-report questionnaire can be used in primary care as a tool enabling general practitioners and internists to decide on further patient routing to corresponding specialists.
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REVIEW ARTICLE
The potential for improving the efficacy of treatment for irritable bowel syndrome with a multi-target drug alverine citrate plus simethicone: The Expert Panel Statement
Abstract
The irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. However, at most, one-third of IBS patients are satisfied with the results of their treatment. A combination of pharmaceuticals or multi-target drugs should be used for the treatment to be effective due to the complexity of IBS pathophysiology. The Russian Expert Panel in gastroenterology, including functional gastrointestinal disorders, currently considered to be disorders of gut-brain interaction, at its open session has discussed the possibilities to increase the efficacy of treatment of patients with IBS with a multitargeted agent alverine citrate combined with simethicone registered under the trade name of Meteospasmyl® (Mayoly Pharma, France) and adopted the respective resolution. Based on the results of multiple experimental and clinical studies, the experts declared that the combination of alverine citrate with simethicone relieves pain through the alleviation of its main mechanisms (spasms, flatulence, visceral hypersensitivity, and inflammation), and normalizes bowel movements demonstrating the normokinetic (eukinetic) properties. All clinical effects of the combination of alverine citrate and simethicone are prolonged. Alverine citrate combined with simethicone improves patients’ quality of life, including their psychological well-being. Due to the efficacy and good safety profile, it is possible to use the combination of alverine citrate and simethicone as on-demand and ex juvantibus treatment. The combination of alverine citrate and simethicone is a single selective antispasmodic that allows for a simultaneous solution of two clinical challenges: to rid the patient of abdominal pains and to properly prepare the patient for instrumental examinations (colonoscopy, abdominal ultrasound, and radiological examination), due to a high simethicone dose and spasmolytic properties of alverine citrate. In addition, Meteospasmyl® is a single antispasmodic, which has demonstrated high efficacy and safety in a clinical study of its combination with a probiotic (Probiolog® IBS), containing the strains (Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483) acting on all IBS pathogenesis steps. This is extremely important, considering the proven role of gut dysbiosis in IBS pathophysiology.
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