Organ Disease Research Articles

Structure of circulatory system diseases and their genetic predictors in athletes with high intensity of training and competitive load

Introduction: Morphofunctional changes of the circulatory system organs detected in athletes may remain without due attention, as clinical (phenotypic) signs of pathological abnormalities are very similar to manifestations of cardiovascular system adaptation to intensive physical loads. The aim of the study is to propose a personalized algorithm for biomedical support of professional athletes with abnormalities and diseases of the circulatory organs based on clinical and genomic data.Materials and methods: The results of in-depth medical examination (2021-2023) of 15,464 athletes who are members of Russian sports teams were analyzed. The structure of circulatory system diseases according to the codes of the International Classification of Diseases, 10th revision (ICD-10), which were included in the summary report of the last examination, was analyzed. Fifty athletes with abnormalities and diseases of the circulatory system organs, experiencing different degrees of intensity of dynamic and static loads in accordance with the Mitchell classification, were selected from the study sample for full genome sequencing and subsequent clinical interpretation of the obtained data.Results: In the study sample the number of people with pathologic conditions of the circulatory system organs amounted to 6 946 people (45 %). Mitchell classification groups had statistically significant differences with respect to the prevalence of 10 diseases of the circulatory system organs. In 50 DNA samples of professional athletes, 5 probably pathogenic variants (10%), 19 variants with uncertain clinical significance (38%), relevant to the phenotype of a monogenic disease with circulatory system organ damage, were detected.Conclusion: Molecular genetic testing is an effective tool for differential diagnostics of pathologic and adaptive changes in the organs of the circulatory system. Carrying causative genes in combination with clinical signs allows to change the tactics of medical and biological support of an athlete according to the proposed algorithm.

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Current understanding of circular RNAs in preeclampsia.

Preeclampsia (PE) is a multiple organ and system disease that seriously threatens the safety of the mother and infant during pregnancy, and has a profound impact on the morbidity and mortality of the mother and new babies. Presently, there are no remedies for cure of PE as to the mechanisms of PE are still unclear, and the only way to eliminate the symptoms is to deliver the placenta. Thus, new therapeutic targets for PE are urgently needed. Approximately 95% of human transcripts are thought to be non-coding RNAs, and the roles of them are to be increasingly recognized of great importance in various biological processes. Circular RNAs (circRNAs) are a class of non-coding RNAs, with no 5' caps and 3' polyadenylated tails, commonly produced by back-splicing of exons. The structure of circRNAs makes them more stable than their counterparts. Increasing evidence shows that circRNAs are involved in the pathogenesis of PE, but the biogenesis, functions, and mechanisms of circRNAs in PE are poorly understood. In the present review, we mainly summarize the biogenesis, functions, and possible mechanisms of circRNAs in the development and progression of PE, as well as opportunities and challenges in the treatment and prevention of PE.

The effect of the drug L-carnitine when administered intramuscularly on the blood parameters of rats

L-carnitine is a vitamin-like substance that plays an important role in the transport of fatty acids and their further use as an energy source. Most studies have identified beneficial effects of using L-carnitine for preventive and therapeutic purposes. The series of publications reviewed is devoted to the study of the results of the use of L-carnitine in metabolic disorders, diseases of various organs, organ systems, the central nervous system, as well as to elucidate the possible reasons for the decrease in the level of L-carnitine in the body. To date, L-carnitine is used in the Russian Federation only in the form of a feed additive; the purpose of our study was to study L-carnitine in the form of an injection solution. Toxicity studies were conducted on outbred rats in October 2021 in the vivarium of the St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190-210 grams. When studying subchronic toxicity when administered intra-muscularly, L-carnitine was administered at 2 dose levels. 1/5 and 1/10 of the maximum tolerated dose in acute toxicity studies. In this regard, three groups of animals were formed. The first experimental group (n=10) was administered the drug intramuscularly at a dose of 0.08 mg/kg, the second group (n=10) at a dose of 0.04 mg/kg. The control group (n=10) was intramuscularly injected with a 0.09% sodium chloride solution at a dose of 0.08 mg/kg. The study was carried out over 42 days. Biological material samples were taken from 5 animals from each group the next day after the end of the drug administration (day 43), and 10 days after the last drug administration (day 53). The results of the study showed that dosages of 1/5 and 1/10 of the maximum tolerated do not cause external signs of toxicosis and death in rats. No significant changes were found in the biochemical parameters of the blood of animals in the experimental and control groups.

Multiparameter gas sensor based on UV-SFR combined with wavelet transform-neural network at ppb level

Abnormal concentrations of nitric oxide (NO), ammonia (NH3), carbon disulfide (CS2) and sulphur dioxide (SO2) in exhaled breath are closely associated with diseases in specific organs of the body. Meanwhile, the above gases are also common pollutants in the atmosphere, and effective online detection of them plays a key role in disease prevention and environmental pollution prevention. This study reports a multiparameter gas sensor system based on the combination of ultraviolet segmented fitting reduction (UV-SFR) and wavelet transform-neural network (WT-NN) model for simultaneous online detection of the concentrations of NO, NH3, CS2 and SO2. Firstly, to avoid the occurrence of spectral baseline drift and absorption peak intensity reduction, a UV-SFR method is proposed for the discrete single peak type absorption spectra contained in the UV spectra. Our method can remove the slow change absorption induced by other factors, and ultimately obtain the differential absorption spectra of the gas mixtures. Then, the WT is used to denoise the differential absorption spectra of the gas mixtures. Next, for the presence of severe spectral line overlap in gas mixtures, the NN model is built based on the denoised spectral data. Finally, transfer learning is introduced into NN to improve the detection accuracy. The experimental results show that the sensor system can reliably achieve simultaneous online detection of NO, NH3, CS2, and SO2 at ppb level, and the average absolute errors of their measurements are 0.96 ppb, 1.27 ppb, 0.76 ppb and 0.97 ppb, with measurement accuracies of 3.5 %, 0.8 %, 0.5 % and 0.9 %, respectively.

SONOGRAPHIC PARAMETERS IN THE DIAGNOSIS OF CHRONIC CERVICITIS

Introduction. Inflammatory diseases of the pelvic organs (IDPO) remain the most relevant issue in contemporary gynecology. In modern diagnostics of reproductive organ pathologies, a highly effective and accessible method is ultrasound examination. Recent studies in this field, conducted using high-frequency digital transvaginal echography, have significantly contributed to reevaluating the potential of ultrasonographic diagnosis of the cervix; however, further research is warranted.
 The aim of this research is to enhance the diagnosis of cervical changes in cervicitis.
 Materials and methods. The study included 68 women with chronic cervicitis. The diagnosis was established based on clinical, colposcopy, and bacterioscopist examinations. During transvaginal ultrasound examinations, the cervix was visualized in both longitudinal and transverse projections for all patients. The patients with chronic cervicitis were divided into two groups: Group I consisted of 37 patients with visual changes in the cervix, while Group II comprised 31 women without any changes. A comparison group included 35 healthy women.
 Results. Chronic cervicitis is characterized by an increase in the thickness and volume of the cervix, as well as the heterogeneity of the stroma due to cystic cavities, with elevated ratios of cervix thickness to length and endocervix thickness to cervix thickness. Significant sonographic signs of the inflammatory process in the endocervix also include certain structural features, such as indistinct contours, increased echogenicity, small cysts, and multiple microcalcifications in the endocervix, uneven dilation of the cervical canal, and an area of reduced echogenicity.
 Conclusions. Therefore, a thorough ultrasound examination to determine the condition of the cervix, thickness, and structure of the endocervix can be a valuable adjunct non-invasive tool in the diagnosis of chronic cervicitis and can assist clinicians in diagnosing this pathology even in cases where there are no visual changes in the cervix during an examination.

Emerging Insights into the Role of BDNF on Health and Disease in Periphery.

Brain-derived neurotrophic factor (BDNF) is a growth factor that promotes the survival and growth of developing neurons. It also enhances circuit formation to synaptic transmission for mature neurons in the brain. However, reduced BDNF expression and single nucleotide polymorphisms (SNP) are reported to be associated with functional deficit and disease development in the brain, suggesting that BDNF is a crucial molecule for brain health. Interestingly, BDNF is also expressed in the hypothalamus in appetite and energy metabolism. Previous reports demonstrated that BDNF knockout mice exhibited overeating and obesity phenotypes remarkably. Therefore, we could raise a hypothesis that the loss of function of BDNF may be associated with metabolic syndrome and peripheral diseases. In this review, we describe our recent finding that BDNF knockout mice develop metabolic dysfunction-associated steatohepatitis and recent reports demonstrating the role of one of the BDNF receptors, TrkB-T1, in some peripheral organ functions and diseases, and would provide an insight into the role of BDNF beyond the brain.

Primary Sjögren’s syndrome independently promotes premature subclinical atherosclerosis

ObjectivesCardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren’s syndrome (pSS). Correlations with clinical factors such as...

IJCM_171A: A community-based study on awareness of organ donation among in Arang block of Raipur district Chhattisgarh.

Background: For many of the end-stage organ diseases, organ transplantation is the most preferred treatment. The need for the organ transplantation is higher than the availability. For the transplantation program to be successful, awareness regarding organ donation is needed and people must have a positive attitude toward donating organs. Objective: To determine the knowledge, attitudes, and practices regarding organ donation in Arang block of Raipur district Chhattisgarh. Methodology: Community based cross-sectional study used in this study. Simple random sampling was used to generate a sample of 100 in Arang block of Raipur district. Face to Face interview was conducted based on a semi structured questionnaire in Arang block of Raipur district. Data was taken from MS Excel sheet and analysed. Results: The majority of the study participants belongs to 44.9 year average mean with 15.4 Standard deviation. 65% of respondents were male and 35% were female. The study shows that 64% of respondents studied high school or above. Per capita income of 40% belong to Lower class 5. Majority of respondents have good knowledge and 75% have positive attitude for organ donation. Conclusion: The present study concluded there was good knowledge among the community participants. However, there questionnaire were kept distinct keeping in mind to their level of knowledge. Attitude variable didn’t have much disparity.

Why Altruistic Organ Donations Are Not Meeting Demands.

Solid-organ transplantation remains the optimal therapeutic option for end-stage organ disease. Altruistic donation represents the ultimate sign of generosity and the most important gift of life. Currently, <10% of the global needs for transplant are fulfilled. Organ shortages result from an inability to provide an adequate organ supply to match demands. The recently observed stagnation in living kidney donations in the United States is related to a drop in all types of organ donations from living related donors, which has been paralleled with a steady and continuous increase in all living unrelated donations. Some forms of living unrelated donation represent a financially driven survival system within which wealthy recipients exploit poor donors. Low rates of altruistic donation are related to cultural barriers, religious obstacles, fear, and consequent distrust in the system. The low rate indicates a state of lack of societal solidarity, a consequence of the state of subconsciousness at the individual and collective levels that humanity is living in. Human domestication, the conditioning process that humans go through since birth and the primary facilitator of this subconscious state, is guarded through familial, social, cultural, religious, political, and mass media organizations, which are all under the influence of the monetary establishment. Acquired beliefs, mainly during the domestication process, influence our perception of the environment, our values, and ultimately our way of life. Unfortunately, this conditioning process is negatively enforced, leading to a stressful state. The powerful subconscious mind places humans in a permanent survival mode, resulting in loss of intelligence, indispensable for well-being and happiness. Altruistic donation requires a close cooperation between all parties involved in the donation process and necessitates a positive reprograming of our subconscious based on sharing, generosity, satisfaction, gratitude, trust, inner peace, and ultimately happiness, well-known constituents of unconditional love, which represents the peak of consciousness.

IJCM_368A: Knowledge, attitude and practice on organ donation among college students in madurai district, Tamil Nadu - a cross-sectional study

Background: The mainstay treatment for end-stage organ disease is transplantation as it improves the quality of life for organ recipients1. Though National Organ Transplant Programme is functioning well, the number of end stage organ deaths stands at 500000/year. Hence the need of present study conducted among students as they serve as health messengers for any Public Health Programme to succeed. Objective: 1. To assess Knowledge, Attitude and Practice [KAP] on Organ Donation among College students, Madurai district. 2. To determine association between Socio-Demographic characters like Gender, Age, Religion with Knowledge and Attitude on Organ Donation among the study population. Methodology: This Cross-sectional study on organ donation was conducted among 550 Arts College students in Madurai District from September to October 2023 using Multi stage Sampling and Sample size was estimated by using Kinge A et al3. After obtaining informed consent, study population was interviewed using Semi Structured Questionnaire containing 4 sections including KAP and Socio Demographic Profile. For positive questions, each Correct answer was given 1 mark and incorrect answer as 0. Reverse Scoring was assigned to Negative Questions. Data entered in Excel and analysed using SPSS version 21.0. Results: The mean age of participants was 19.57± 2.9 with males 44.54% and Females 55.45%. Hindus were 85.27%, Muslims 6% and Christians 8.72%. Out of 550 Participants, 40.36%(n=222) had adequate Knowledge with mean score of 5.08 ± 0.53, 90.81% (n=505) had Positive attitude, 5 %(n=28) had taken pledge. Chi-square showed statistically significance between Knowledge and Age, gender Conclusion: Regular IEC activities and inclusion of Organ donation as a part of education curriculum are needed to further improve awareness.

Особливості розширеного гінекологічного обстеження в жінок із рецидивним вульвовагінальним кандидозом

The aim of the study - to determine the features of extended gynecological examination in patients with recurrent vulvovaginal candidiasis (RVVC): data from gynecological history, examination, colposcopy, cytological and histological examination to increase the effectiveness of prevention of recurrences in these patients. Materials and methods. A prospective study and clinical-statistical analysis of gynecological history, examination, colposcopy, cytological and histological examination in patients with RVVC was carried out. The main group (MG) consisted of 70 women of reproductive age with RVVC and 40 healthy women of reproductive age, who made up the control group (CG). Results. The most frequent complaint was itching in the vagina - in 32 (45.7%) and itching in the area of the external genitalia, which bothered 29 (41.4%) patients; complaints of dysuric disorders in 19 (27.1%) patients became the reason for an earlier visit, usually to a urologist; dyspareunia occurred in 24 (34.3%) patients. Cervical ectopy with signs of exocervicitis and endocervicitis was found in 20 (28.6%) patients with RVVC; an atypical transformation zone was noted in 15 (21.4%) and was represented by an acetowhite epithelium with clear contours in the transformation zone in 37 (52.8%) p&lt;0.05. At the same time, acetobilious epithelium with punctation was found in 19 (27.1%) patients, acetobilious epithelium with mosaic in 12 (17.1%), simultaneously with punctuation and mosaic in 6 (8.6%) patients. In CG, ectopy without signs of exo- and endocervicitis was observed in 7 (17.5%) patients. A rather high percentage of CIN attracts attention - in 37 (52.8%) of 70 women of MG: of them, CIN I - in 26 (37.1%) women, CIN II - in 9 (12.8%) patients, CIN III - in 2 (2.9%) patients. Conclusions. Subjectively, RVVC was characterized by mild clinical symptoms, at the same time marked inflammatory changes in the lower parts of the genital tract with involvement in the pathological process of the cervix. Every third patient had dysuric disorders against the background of chronic inflammatory diseases of the pelvic organs, which are present in the anamnesis. In most patients, the long recurrent course of the disease was accompanied by psychosomatic disorders, emotional lability. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

A clinical case of surgical treatment of appendiceal stump abscess

In Ukraine, the share of patients with acute appendicitis is 89.1% of the total number of patients with acute surgical pathology. In modern surgical practice, early and late complications occupy the first place in the structure of acute surgical diseases of the abdominal organs, regardless of the age and gender of the patients, and the postoperative mortality is on average 0.15%. In the remote period after an appendectomy, despite the progress of modern surgery, a very rare complication known as inflammation of the stump of the appendix can occur. The patient, 25 years old, turned to the department of purulent surgery with complaints of a «small wound» at the site of the postoperative scar in the right inguinal area and minor purulent discharge from it. Four months ago, in July, he was operated on for acute phlegmonous appendicitis. On November 1, after physical exertion, the wound reappeared, and on November 3, the patient independently sought a consultation at the reception department of the Clinical City Hospital No3. He was examined by a surgeon and hospitalized. During the revision of the wound, a tumor‑like formation measuring 2.5x3.0x2.5 cm, as well as the parietal peritoneum, was revealed. Appendectomy was performed by the method of pouch ligation with drainage of the abdominal cavity through a separate contraperture with polyvinyl chloride drainage. After the operation, a diagnosis was established: abscess of the stump of the appendix, and external fistula of the anterior abdominal wall. The postoperative wound healed with primary tension, and the sutures were removed. The diagnosis of appendicitis may be mistakenly excluded from the clinical search due to the presence of a postoperative scar after appendectomy. A clear clinical picture of acute appendicitis or the opening of a fistula at the site of a postoperative scar in the right iliac region indicates the need for a computer tomography of the abdominal organs with contrast to establish an accurate diagnosis and choose the correct treatment tactics. The only treatment for inflammation of the appendiceal stump is a complete appendectomy with appendix removal either by open or laparoscopic surgery, which should be performed urgently to avoid further complications.

INTERPLAY OF METABOLIC DYSREGULATIONS, OBESITY, PATHOLOGIES OF ABDOMINAL ORGANS, RESPIRATORY ORGANS, CARDIOVASCULAR SYSTEM, AND CHRONIC KIDNEY DISORDERS AS POTENTIAL RISK FACTORS FOR MALIGNANT NEOPLASMS IN THE CONTEXT OF PALLIATIVE MEDICAL PRACTICE

Metabolic changes, obesity, diseases of the abdominal cavity organs, respiratory organs, cardiovascular system, and chronic kidney diseases are risk factors for the development of malignant neoplasms. This poses new challenges in palliative practice: the use of integrated methods, the study of new biomarkers, and the application of modern technologies, the formation of professional readiness of medical personnel for activities in the field of palliative and hospice care. Objective. The study aims to conduct an epidemiological analysis of the prevalence and comorbidity of malignant neoplasms among patients in northern Bukovyna and to analyze the relationship between metabolic changes, obesity, diseases of the abdominal cavity organs and respiratory organs, cardiovascular system, and chronic kidney diseases as risk factors for the development of malignant neoplasms in the context of palliative medical practice. Material and methods. Clinical data of patients, data on metabolic status and obesity, information on the condition of abdominal cavity organs, respiratory organs, cardiovascular system, and kidneys, results of diagnostic tests, as well as applied statistical methods for assessing the relationships between different factors and the risk of malignant neoplasms were utilized.Results. The obtained results indicate a significant impact of metabolic changes, obesity, and diseases of various organs on the increased risk of malignant neoplasms in patients undergoing palliative care. The identified correlations underscore the necessity of an integrated approach to treatment, focused on managing metabolic status and systemic diseases. The discussion complements this by highlighting potential interaction mechanisms and pointing out opportunities for improving palliative care through emphasis on prevention and management of these risk factors.Conclusion. The research highlights the importance of understanding and managing metabolic, organic, and systemic risk factors, as they are interdependent in palliative practice, pointing to potential opportunities for improving treatment outcomes and the quality of life for patients with malignant diseases.

Вплив наркотичної залежності на рівні перекисного окислення ліпідів у жінок із хронічними запальними захворюваннями статевих органів, викликаними інфекціями, що передаються статевим шляхом

Oxidative stress, induced by drug addiction, and its consequences for women's reproductive health, especially in the context of chronic inflammatory diseases of the genital organs caused by sexually transmitted infections (STIs), is one of the significant areas of impact. Aim - to assess the effect of drug addiction on the level of lipid peroxidation (LPO) in women with chronic inflammatory diseases of the genital organs caused by sexually transmitted infections (STIs), which will allow to further determine the ways of correcting the detected changes. Materials and methods. The study investigated the level of LPO in 60 women with chronic inflammatory diseases of the genital organs caused by sexually transmitted infections and with drug and psychotropic substance dependence. Women were divided into 3 groups depending on the quality of drugs and psychotropic substances they abused: the Group 1 - 25 women addicted to several drugs; the Group 2 - 25 women addicted to opioids; the Group 3 - 10 women addicted to sleeping pills or sedatives. The intensity of LPO and the state of the antioxidant system were assessed by the spectrophotometric method. Statistical data processing was performed using the “Data Analysis” package in Microsoft Excel. Results. The study showed that women with drug addiction exhibit increased levels of LPO, indicating a disruption of the antioxidant system and increased formation of free radicals. This can cause damage to cellular membranes and other biomolecules. The use of synthetic opiate receptor antagonist drug in treatment contributed to the normalization of these indicators, pointing to the restoration of the antioxidant system and reducing the risk of further oxidative stress. Conclusions. Drug dependence causes an increase in oxidative stress in women with STIs, which negatively affects their reproductive health. The synthetic opiate receptor antagonist drug can be effective in reducing the levels of LPO and improving the condition of patients. The research was conducted according to principles of Declaration of Helsinki. Protocol of research was proved by local ethical committee, mentioned in institution’s work. Informed consent of women was obtained for the study. No conflict of interests was declared by the authors.

Analysis of the Expression of LSF Transcription Factor in the Regulation of Transcription and TSG101 during the Neoplastic Transformation of Endometrial Cells.

Previous research indicates that carcinogenesis involves disrupting the functions of numerous genes, including factors involved in the regulation of transcription and cell proliferation. For these reasons, in endometrial carcinogenesis, we decided to investigate the expression of TSG101 (a suppressor of tumor transformation) and LSF (a transcription factor involved in numerous cellular processes, such as cell cycle regulation, cell growth, development, and apoptosis). LSF may be involved in the regulation of TSG101 expression. The research material consisted of endometrial cancer samples from 60 patients. The control group consisted of normal endometrium samples donated by 60 women undergoing surgery for benign diseases of the female reproductive organs. The samples were subjected to immunohistochemical staining with antibodies specific to TSG101 and LSF. Specific antibodies were used to identify TSG101 and LSF in the examined histopathological preparations. An approximately 14-fold lower risk of endometrial cancer development was observed in patients with TSG expression in more than 75% of the assessed cells (4% vs. 36%; OR = 0.07; p = 0.0182). There was a four-fold lower risk of endometrial cancer development in patients with LSF expression in more than 50% of the assessed cells (32% vs. 64%; OR = 0.26; p = 0.0262). A more than three-fold lower risk of endometrial cancer development was observed in patients with LSF expression in more than 75% of the assessed cells (24% vs. 52%; OR = 0.29; p = 0.0454). Endometrial cancer was diagnosed in those with a lower level of TSG101 expression than in those with a cancer-free endometrium. Decreased expression of TSG101 may be a marker of endometrial cancer, and increased expression of LSF when diagnosed with endometrial cancer may indicate greater advancement of the disease. These markers might be used as diagnostic and prognostic markers-however, there is a lack of a correlation between them.

Abstract 3827: Optimizing the treatment schedule of radiotherapy combined with VEGFR-TKIs and PD-(L) 1 inhibitors in metastatic colorectal cancer

Abstract Background: The oral vascular endothelial growth factor receptor (VEGFR) inhibitor fruquintinib, an innovative Chinese drug, has recently been approved by the U.S. Food and Drug Administration (FDA) for third-line treatment of metastatic colorectal cancer (mCRC) in adults. This study aims to investigate the efficacy and safety of radiotherapy (RT) combined with VEGFR-TKIs (such as fruquintinib) and PD-(L) 1 inhibitors in mCRC, and explore optimal sequence of RT with the systemic regimen. Methods: This retrospective study enrolled eligible patients with MSS/pMMR mCRC who had received RT in combination with anti-angiogenic drugs (Fruquintinib or Regorafenib) and immunotherapy (IT) between April 2018 and September 2023. Data on treatment response, progression-free survival (PFS), overall survival (OS), and adverse events were collected. Results: A total of 42 pts were analyzed. For Fru + IT + RT (n = 33) and Reg + IT + RT (n = 9), ORR were 21.2% (7/33) and 11.1% (1/9); DCR were 81.8% (27/33) and 88.9% (8/9), respectively. Median PFS were 6.4 mo and 5.0 mo (P=0.856) while median OS were 17.2 mo and 7.2 mo (P=0.578), respectively. In-depth analysis of Fru + IT + RT treated population, the PFS and OS of 3rd-line treatment were superior to later (≥ 4th) -line treatment (median: 6.7 vs 4.2 mo, P=0.02) and (median: 17.5 vs 8.9 mo, P=0.27), seemingly. Additionally, RT before initiation of Fru + IT demonstrated superior PFS compared to simultaneous/sequential RT with Fru + IT (median 7.1 vs 6.1 vs. 3.2 mo, p&amp;lt;0.001). Simultaneously, pts with interval time ≤1 month, received numerically benefit compared to interval time &amp;gt;1 month between RT and FRU+IT (mPFS: 6.2 vs. 3.8 mo, P=0.16; mOS: not reached vs. 7.65 mo, P=0.08). Further subgroup analysis revealed that men, age ≤56 years, ECOG PS score of 1, primary focal resection, recurrent metastatic disease, liver/pulmonary metastases, and metastatic involvement of organs ≥2, were more favorably treated with Fru for prolonged OS. Intriguingly, the 3rd-line treatment of Fru exhibited a tendency to prolong OS compared to Reg. Cox multivariate regression analysis suggested that the cycle of Fru/Reg combined with PD-1 inhibitor treatment was a common independent influencing factor for PFS and OS. Safety was consistent with previous reports, and the incidence of AE appeared to be lower in Fru + IT + RT than in Reg + IT + RT. Conclusion: In pts receiving RT of localized lesions, the addition of Fru combined with PD-1 inhibitor could prolong the pts' OS more than Reg plus PD-1 inhibitor. And radiotherapy sequential Fru + IT (interval time ≤1 mo) treatment is expected to be the optimal strategy for MSS/pMMR mCRC. Citation Format: Zhenyu Lin, Menglan Zhai, Tao Zhang. Optimizing the treatment schedule of radiotherapy combined with VEGFR-TKIs and PD-(L) 1 inhibitors in metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3827.

Aberrant tumor vasculature. Facts and pitfalls.

Endothelial cells form a single cell layer lining the inner walls of blood vessels and play critical roles in organ homeostasis and disease progression. Specifically, tumor endothelial cells are heterogenous, and highly permeable, because of specific interactions with the tumor tissue environment and through soluble factors and cell-cell interactions. This review article aims to analyze different aspects of endothelial cell heterogeneity in tumor vasculature, with particular emphasis on vascular normalization, vascular permeability, metabolism, endothelial-to-mesenchymal transition, resistance to therapy, and the interplay between endothelial cells and the immune system.

PACULIARITIES OF CLINICAL PRESENTATION, DIAGNOSIS, AND TREATMENT FOR INJURIES OF THE LARGE SALIVARY GLANDS

Background. Salivary gland lesions of various genesis are quite widespread among patients, tumorous processes involving these organs make up 2.2-3.7% of the total number of head and neck tumors, 78-82% of salivary gland tumor cases, and sialoadenitis, which makes 3.8-6.7% of the total number of inflammatory diseases of maxillofacial organs. The initial diagnostic imaging for parotid gland tumors typically involves an ultrasound examination; however, it does not definitively indicate the need for surgical intervention. While computed tomography or magnetic resonance imaging are not obligatory elements of patient assessment, they may be recommended in specific instances to facilitate accurate treatment planning.&#x0D; Fine-needle aspiration biopsy can serve as an obligatory diagnostic test, irrespective of whether an ultrasound examination has been conducted, particularly when there are suspicions of atypical presentations of polymorphic adenoma. Incisional biopsy is contraindicated, as it frequently leads to neoplastic implantation, thereby increasing the risk of recurrence of polymorphic adenomas and malignant neoplasms.&#x0D; The purpose of the study is to conduct a comparative analysis of the data of clinical examinations, laboratory tests, surgical treatment, complications and postoperative results, taking into account the prevalence of tumor and inflammatory processes of the parotid salivary glands.&#x0D; Material and methods. We have conducted a retrospective study of the medical histories of 174 patients operated on at the Department of Maxillofacial Surgery of the “Poltava Regional Clinical Hospital named after M.V. Sklifosovsky”.&#x0D; Results. According to our data, pleomorphic adenoma was the most common benign tumor, and mucoepidermoid carcinoma was the most frequently detected malignant tumor. Regarding initial presentations, the primary observation was a tumor mass in 96.1% of all cases. Additional findings included incidental lesions detected during imaging studies and localized pain or inflammation. Isolated occurrences of inadvertent lesions during imaging of neoplasms have also been documented. Palpation was recognized as an excellent clinical parameter for topographic localization and classification of lesions for malignancy, with proven value in the specimen due to its high sensitivity for demonstrating nodules in the superficial lobe (97.1%) and high specificity for nodules in the deep lobe. We established that the average evolution time of benign tumors was approximately three times longer than that of malignant tumors. These data are consistent with literature data that malignant tumors are more aggressive and have a rapid evolution, while benign, in turn, have an insidious onset and slow growth. During intraoperative examination, high specificity is desirable because it can reliably exclude malignancy, preventing unnecessary radical interventions. Another intervention that we have analyzed in the treatment of benign tumors is dermal parotidectomy, which showed a recurrence rate similar to superficial parotidectomy, although with a lower rate of serious complications (12.4% less on average). It has been found that the choice of this intervention is mainly related to the incidence of recurrence, and in 51-56% of cases in patients with a previous fine-needle aspiration biopsy.&#x0D; Conclusion. According to this study, taking into account the experience of our clinic, the presence and visualization of a single nodule in the parotid area is the main clinical manifestation of parotid gland cancer. Pleomorphic adenoma is the most common histological type, and facial nerve-sparing subtotal parotidectomy is the best treatment for these patients.

In-hospital ischemic stroke in ophthalmic patients

Justifi cation. Due to the high prevalence of diseases of the visual organs (cataracts, glaucoma, etc.) and the large number of surgical interventions performed annually in elderly and senile people, the prevention of in-hospital ischemic stroke (IHS) is an urgent task.The purpose of the work. To study the risk factors of development, characteristics of care and outcomes of IHS in ophthalmic patients.Material and methods. The study was performed in the period from 01.01.2022 to 31.12.2022 on the basis of ophthalmological departments specializing in the performance of planned vitreoretinal surgical interventions, two large multidisciplinary hospitals in St. Petersburg.Results. It has been established that perioperative ischemic stroke (included in the structure of the IHS) is a rare complication of minimally invasive ophthalmic operations. Its share was 0.07% (n = 5) of the total number of patients who underwent elective ophthalmological intervention during the year; the total share of patients with IHS (taking into account 4 cases of ischemic stroke in the preoperative period) was 0.13%. Most strokes (n = 5; 55.6%) belonged to the cardioembolic subtype, the proportion of using reperfusion techniques was high and amounted to 33.3% (2 endovascular interventions, 1 systemic thrombolysis); the proportion of adverse outcomes was 22.2% (n = 2). A distinctive characteristic of patients with IHS was a combination of high comorbidity with insuffi cient antithrombotic prophylaxis, which consisted in the cancellation of antiplatelet agents and anticoagulants in the preoperative period.Conclusion. Current recommendations on perioperative management of patients indicate the need to continue taking antiplatelet and anticoagulant drugs for most ophthalmic operations, due to the predominance of threats of thromboembolic complications over the risk of retrobulbar bleeding.