Significant Pathology Research Articles

Imaging Outcomes of Emergency MR Imaging in Dizziness and Vertigo: A Retrospective Cohort Study.

Patients exhibiting acute dizziness or vertigo often represent a diagnostic challenge, and many undergo neuroimaging for stroke detection. We aimed to demonstrate the imaging outcomes of first-line emergency MR imaging among patients with acute dizziness or vertigo and to determine the clinical risk factors for stroke and other acute pathology. This retrospective study included consecutive patients with acute dizziness or vertigo referred for emergency MR imaging in a tertiary hospital during 5 years. We recorded and analyzed patient characteristics, relevant clinical information, and imaging outcomes. Risk score models were derived to predict which patients were more likely to present with positive MR imaging findings. A total of 1169 patients were included. Acute stroke was found in 17%; other clinically significant pathology, in 8% of patients. In 75% of the patients, emergency MR imaging showed no significant abnormalities. Risk factors for acute stroke included older age, male sex, and a prevalence of cardiovascular risk factors and neurologic signs. Isolated dizziness had no discriminative power on imaging outcomes, and 14% of these patients showed acute stroke. Risk scores had only moderate performance in predicting acute ischemic stroke (receiver operating characteristic area under curve = 0.75) or any significant pathology (receiver operating characteristic area under curve = 0.70). Acute dizziness and vertigo remain challenging even when emergency MR imaging is readily available. One in 4 patients had acute pathology on MR imaging. Predictors for acute pathology (older age, male sex, cardiovascular risk factors, and neurologic signs) may aid in patient selection for MR imaging, optimizing the yield and clinical impact of emergency neuroimaging. Low diagnostic yields of CT and internal acoustic canal MR imaging may offer an opportunity to reduce health care expenditures in the future.

SOME FEATURES OF CELLULAR ENERGY SUPPLY OF THE BODY IN PREMATURE INFANTS WITH SEVERE FORMS OF PERINATAL PATHOLOGY

The nature of postnatal adaptation of newborns, their further growth, development, health status and quality of life largelydepend on the well-being of intrauterine development and maturity at birth. Premature birth under hypoxia causes signifi cant metabolic disorders in the body, is accompanied by a high risk of severe organ dysfunction, which requires in-depth research to clarify the features of intracellular metabolism in order to further improve methods of diagnosis and treatment of newborns with various forms of perinatal pathology.Aim of the research. To study the trends of changes in energy metabolism in premature infants with severe forms of perinatal pathology to investigate the possibility of using them as additional criteria of hypoxic damage to the body in conditions of morphological and functional immaturity.Materials and methods. Clinical and laboratory examinations were performed on 68 newborns with severe forms of perinatal pathology at the gestational age of 32 to 34 weeks; the comparison group consisted of 27 conditionally healthy newborns at the gestational age of 34 to 37 weeks. Inclusion criteria for the main study group: gestational age at birth from 32 to 34 weeks, clinical signs of severe perinatal pathology. Exclusion criteria: gestational age at birth < 32 and ≥ 37 weeks, diagnosed congenital malformations and septic conditions. The list of diseases was determined according to the International Classifi cation of Diseases, X Revision. The following blood serum laboratory parameters were studied: lactate level, glycerol-3-phosphate dehydrogenase (GPDH) (EC 1.1.99.5), succinate dehydrogenase (SDH), NADH dehydrogenase (NADH) (EC 1.6.5.3); the electron transport chain coeffi cient (ETC) was calculated. Laboratory studies were performed using micromethods. The study was conducted in accordance with the provisions of GCP (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (April 4, 1997), the Declaration of Helsinki of the World Medical Association (1964-2008), Order of the Ministry of Health of Ukraine No. 690 dated September 23, 2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 dated July 12, 2012). Protocol of scientifi c research of the Biomedical Ethics Committee of BSMU dated September 12, 2015. Informed written consent was obtained from the parents of the patients before the study with an explanationof the purpose, objectives and methods of laboratory testing. Statistical processing of the results was performed using STATISTICA software (StatSoft Inc., USA, version 10). Comparison of quantitative indicators with normal distribution was performed using Student’s t-test, and the probability of diff erences was considered statistically signifi cant at p<0.05. The complex of studies was conducted within the framework of the planned research topics of the Department of Pediatrics, Neonatology and Perinatal Medicine of the Bukovinian State Medical University: «Improvement of the areas of prognosis, diagnostics and treatment of perinatal pathology in newborns and infants, optimization of the schemes of catamenial observation and rehabilitation» (State registration No. 0115U002768, term of execution 01.2015-12.2019) and «Chronobiological and adaptive aspects and features of vegetative regulation in pathological conditions in children of diff erent age groups» (State registration No. 0122U002245, term of execution 01.2020-12.2024).Results. In newborns of the main group, in comparison with the control group, a signifi cant decrease in GFDH and SDHwas found, which indicates a signifi cant impairment of the activity of enzymes of the respiratory chain and explains the lack of oxygen absorption in the body at the cellular and tissue level, causing the severity of the condition of newborns. Determination of the level of GPDH and SDH in the dynamics of observation in children showed some improvement in these indicators. In the severe condition of newborns, a signifi cant increase in the NADPH index was found, with a further probable increase in its level in the dynamics of observation. Calculations of ETC coeffi cient in cord blood showed a signifi cant decrease of this indicator in comparison with the control group. The identifi ed disorders of intracellular energy metabolism under hypoxia indicate the expediency of conducting comprehensive scientifi c research to study the possibilities of appropriate pharmacological correction to improve the eff ectiveness of treatment of severe forms of perinatal pathology in premature infants.Conclusions: 1. The results of the study revealed a signifi cant decrease in GPDH and SDH at elevated levels of NADPH andETC coeffi cient, which confi rms the presence of signifi cant disturbances in intracellular energy metabolism and mitochondrial oxidation processes. 2. Timely detection of metabolic disorders with the determination of mitochondrial oxidation, in particular energy metabolism, is an important area for improving diagnostic measures in severe forms of perinatal pathology in preterm infants with hypoxic damage to the body in the pathogenesis.

The role of tubular cells in the pathogenesis of Fabry nephropathy

The pathophysiology of Fabry nephropathy (FN) is induced by galactosidase A deficiency with a chronic exposure of glycolipids to every lineage of renal cells. Tissue damage is attributed to the activation of molecular pathways, resulting in tissue fibrosis and chronic kidney disease. Podocytes have been the primary focus in clinical pathophysiological research because of the striking accumulation of large glycolipid deposits observable in histology. Yet, the tubular interstitium makes up a large portion of the whole organ, and therefore, its role must be further considered in pathogenic processes. In this review, we would like to propose Fabry tubulopathy and its ensuing functional effects as the first pathological signs and contributing factors to the development of FN. We will summarize and discuss the current literature regarding the role of tubular cells in Fabry kidney pathophysiology. Starting from clinical and histological evidence, we will highlight the data from animal models and cell cultures outlining the pathophysiological pathways associated with tubular interstitial injury causing renal fibrosis in Fabry nephropathy.

Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm

AimsSignificance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. Materials and MethodsBilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. ResultsIn non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). ConclusionA two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.

[Current and Future Status of Muscle Pathology: The Position of Muscle Pathology Diagnosis in the Future].

Many muscle disease names are mostly based on muscle pathology findings. Naturally, muscle pathology is important in the diagnosis of muscle diseases. Moreover, in recent years, extensive genetic analysis and autoantibody testing for myositis have been applied clinically, although muscle biopsies are less performed. However, muscle pathology should be proactively considered when a single gene presents multiple phenotypes, when variants of unknown pathological significance are detected, or in cases of autoimmune myositis that may be misdiagnosed as muscular dystrophy.

An activity-based sensing fluorescent probe for monitoring endogenous peroxynitrite in Alzheimer's disease models

Alzheimer's disease (AD) is a common neurodegenerative disease that brings great suffering and heavy economic burden to patients. Increasing evidence suggests that peroxynitrite (ONOO−) plays a crucial role in the pathogenesis of AD by mediating neurotoxicity and neuroinflammation. Developing effective peroxynitrite probes to monitor ONOO− is of great significance for the investigation and diagnosis of AD. Herein, two molecular fluorescent probes (NBD-Y and NBD-I) bearing a 7-nitro-2,1,3-benzoxadiazole (NBD) moiety were designed and synthesized for specific ONOO− detection. NBD-Y and NBD-I exhibited a rapid response (within 3 s), low detection limits (11 and 45 nM, respectively), high aqueous solubility (DMSO/PBS = 1: 199, v/v), high selectivity, excellent blood-brain barrier (BBB) penetrability (log P = 3.397), and a ∼78-fold decrease in fluorescence intensity in response to ONOO−. High-resolution mass spectrometry (HRMS), High-performance liquid chromatography (HPLC), and density functional theory (DFT) calculation results indicated that ONOO− may oxidatively break the C-N bond of the probe, resulting in a blue shift of the absorption spectrum due to the principle of intramolecular charge transfer (ICT). Furthermore, NBD-Y has been successfully applied for the detection of endogenous ONOO− in SH-SY5Y cells and is further employed for in vivo imaging in AD mouse models. These results denoted that NBD-Y may serve as a potential biological tool for further understanding the distinct physiological and pathological significance of ONOO−.

The diagnostic and prognostic value of tau-PET in amnestic MCI with different FDG-PET subtypes.

Mild cognitive impairment presenting with an amnestic syndrome (aMCI) and amyloid positivity is considered due to AD. Many subjects, however, can show an overall very slow progression relevant for differential diagnosis, prognosis, and treatment. This study assessed PET biomarkers, includingbrain glucose metabolism, tau, and amyloid load, in a series of comparable aMCI at baseline, clinically evaluated at follow-up. We included 72 aMCI subjects from Geneva Memory Center (N = 31) and ADNI cohorts (N = 41), selected based on available FDG-PET, tau-PET, amyloid-PET, and clinical follow-up (2.3 years ± 1.2). A data-driven algorithm classified brain metabolic patterns into subtypes that were then compared for clinical and PET biomarker measures and cognitive decline. Voxel-wise comparisons were performed both with FDG-PET and tau-PET data. The algorithm classified three metabolic subtypes, namely "Hippocampal-sparing with cortical hypometabolism" (Type1; N = 27), "Hippocampal and cortical hypometabolism" (Type 2; N = 23), and "Medial temporal hypometabolism" (Type 3; N = 22). Amyloid positivity and tau accumulation in the medial temporal and neocortical regions characterized Type 1 and Type 2, whereas Type 3 showed no significant tau pathology, variable amyloid positivity, and stability at follow-up. All tau-positive patients, independently of the FDG-based subtype, showed faster cognitive decline. aMCI subjects can differ in metabolic patterns, tau and amyloid pathology, and clinical progression. Here, we complemented with PET tau biomarker the specific brain hypometabolic patterns at the individual level in the prodromal phase, contributing to the patient's classification. Tau PET is the most accurate biomarker in supporting or excluding the AD diagnosis in aMCI across metabolic subtypes and also predicting the risk of decline.

Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy.

Breast cancer (BCA) remains the leading cause of cancer-related mortality among women worldwide. This review delves into the therapeutic challenges of BCA, emphasizing the roles of interleukin-13 receptor α2 (IL-13Rα2) and erythropoietin-producing hepatocellular receptor A2 (EphA2) in tumor progression and resistance. Highlighting their overexpression in BCA, particularly in aggressive subtypes, such as Her-2-enriched and triple-negative breast cancer (TNBC), we discuss the potential of these receptors as targets for chimeric antigen receptor T-cell (CAR-T) therapies. We examine the structural and functional roles of IL-13Rα2 and EphA2, their pathological significance in BCA, and the promising therapeutic avenues their targeting presents. With an in-depth analysis of current immunotherapeutic strategies, including the limitations of existing treatments and the potential of dual antigen-targeting CAR T-cell therapies, this review aims to summarize potential future novel, more effective therapeutic interventions for BCA. Through a thorough examination of preclinical and clinical studies, it underlines the urgent need for targeted therapies in combating the high mortality rates associated with Her-2-enriched and TNBC subtypes and discusses the potential role of IL-13Rα2 and EphA2 as promising candidates for the development of CAR T-cell therapies.

The Protective Effects of Vanillic Acid and Vanillic Acid-Coated Silver Nanoparticles (AgNPs) in Streptozotocin-Induced Diabetic Rats.

The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (n = 6) for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at P = 0.05) increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly increased the antioxidant and antidiabetic activity and reduced inflammation when compared to using vanillic acid alone.

Is Cranial Imaging Necessary in Children with First-Time Focal Seizures?

Objective: Seizures in children represent a common cause of admission to the emergency department. This study aimed to determine clinically significant intracranial abnormalities in children presenting to the pediatric emergency department with first-time focal seizures.
 Methods: Patients aged 1 month-18 years, who presented to the pediatric emergency department with first-time focal seizures between 2009 and 2019, were retrospectively screened. Patients with a history of trauma, cases in which focal neurological signs could not be assessed, and patients with pre-existing structural brain or neurological abnormalities, and metabolic disorders were excluded from the study. Cranial computed tomography findings were re-evaluated by a pediatric radiologist. The fourth and fifth-level according to the classification of the International League Against Epilepsy were interpreted as urgent intracranial pathologies requiring medical or surgical intervention. The univariate analysis was performed using the chi-square test for categorical data and the Mann-Whitney U test for continuous data.
 Results: The mean age of the 121 patients was 46.8±44.4 months, and 52.9% were male. Clinically significant emergency intracranial pathologies were detected in the neuroimaging of eight patients. Intracranial masses, bleeding, and hematomas were the most common pathologies. The presence of focal neurologic findings and an age below six months were clinically determined as predictors of an urgent intracranial pathology.
 Conclusion: We found the rate of urgent cranial pathologies to be 6.6% in patients presenting to the emergency department following the first focal seizure. Children younger than six months with focal neurological signs should be evaluated for emergency neuroimaging.

Cystic Features in Renal Epithelial Neoplasms and Their Increasing Clinical and Pathologic Significance.

Most cystic renal tumors after resection (Boniak IIF to IV cysts) have an indolent course despite the significantly higher proportion of malignant [ie, renal cell carcinoma (RCC)] diagnosis. Most cystic renal tumors have clear cell histology that include cystic clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (MCNLMP). There is growing evidence to suggest that MCNLMP, cystic clear cell RCC, and noncystic clear cell RCC form a cystic-to-solid biological spectrum with MCNLMP representing the most indolent form and with cystic clear cell RCC behaving better than noncystic (solid) clear cell RCC. Extensively (>75%) cystic clear cell RCC also has an excellent outcome similar to MCNLMP stressing the need to reevaluate the histologic criteria that separate these 2 cystic clear cell tumors. Other tumors with clear cells that can be extensively cystic such as the recently reclassified noncancerous clear cell papillary renal tumor and the newly described MED15::TFE3 RCC also have indolent course and may mimic MCNLMP. Cystic features occur also in renal tumors with nonclear cell histology including tumors capable of metastasis such as acquired cystic disease-associated, tubulocystic, fumarate hydratase-deficient, and eosinophilic solid and cystic RCCs. Cystic imaging presentation of some renal tumors such as papillary RCC can be attributed in part to pseudocystic necrosis and hemorrhage. It is important to know that tubulocystic RCC may have a lower Bosniak class presentation that overlaps with benign renal cysts (Bosniak I to IIF) that are managed conservatively. This review highlights the cystic renal tumors with clear cell and nonclear cell morphologies including some novel RCC subtypes that may have cystic features. The presence of cystic features and their extent may aid in the classification and prognostication of renal neoplasms underscoring its increasing importance in the pathologic diagnosis and reporting of renal neoplasia.

The impact of treatment on endometrium ultrasound findings in reproductive age women with chronic endometritis

Purpose: to evaluate the dynamics of ultrasound parameter of structural changes of endometrium in B-mode before and after therapy in reproductive age women with chronic endometritis.Material and methods. A retrospective cohort study of 158 reproductive age patients (34.5 ± 6.5 years) with a established diagnosis of chronic endometritis was carried out. Ultrasound was performed twice prior and after comprehensive etiotropic therapy in the proliferative phase of the menstrual cycle with measurements of uterus volume, endometrium thickness and volume, with calculation of endometrial/uterine volume percentage ratio. Echogenicity and structure, including the presence of polyps, liquid in the uterine cavity, gas in   the endometrial layer or on midline, the line of endometrial layers closure and the contour of endometrial midline were assessed.Results. There was no complete regress of any of pathological signs after treatment, but the frequency of most of them decreased significantly (p < 0.05). At the same time, there was no significant changes in such signs as heterogeneous structure and increased echogenicity of the endometrium (p > 0.05). In addition, a statistically significant decrease of endometrium thickness and volume, as well as endometrial/uterine volume ratio was obtained with a constant uterus volume (p < 0.05).Conclusion. The dynamic decrease in the frequency of revealing of the ultrasound signs in chronic endometritis on the background of comprehensive etiotropic therapy allows to assess a positive therapeutic benefits.

Incidence of surgically treated chronic subdural hematoma after head injury with normal initial computed tomography

PurposeThe objective was to determine the incidence of surgically treated chronic subdural hematoma (cSDH) within six months after head trauma in a consecutive series of head injury patients with a normal initial computed tomography (CT).MethodsA total of 1941 adult patients with head injuries who underwent head CT within 48 h after injury and were treated at the Tampere University Hospital’s emergency department were retrospectively evaluated from medical records (median age = 59 years, IQR = 39–79 years, males = 58%, patients using antithrombotic medication = 26%). Patients with no signs of acute traumatic intracranial pathology or any type of subdural collection on initial head CT were regarded as CT negative (n = 1573, 81%).ResultsTwo (n = 2) of the 1573 CT negative patients received surgical treatment for cSDH. Consequently, the incidence of surgically treated cSDH after a normal initial head CT during a six-month follow-up was 0.13%. Both patients sustained mild traumatic brain injuries initially. One of the two patients was on antithrombotic medication (warfarin) at the time of trauma, hence incidence of surgically treated cSDH among patients with antithrombotic medication in CT negative patients (n = 376, 23.9%) was 0.27%. Additionally, within CT negative patients, one subdural hygroma was operated shortly after trauma.ConclusionThe extremely low incidence of surgically treated cSDH after a normal initial head CT, even in patients on antithrombotic medication, supports the notion that routine follow-up imaging after an initial normal head CT is not indicated to exclude the development of cSDH. Additionally, our findings support the concept of cSDH not being a purely head trauma-related disease.

Significance of the Wnt signaling pathway in coronary artery atherosclerosis.

The progression of coronary atherosclerosis is an active and regulated process. The Wnt signaling pathway is thought to play an active role in the pathogenesis of several cardiovascular diseases; however, a better understanding of this system in atherosclerosis is yet to be unraveled. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were used to quantify the expression of Wnt3a, Wnt5a, and Wnt5b in the human coronary plaque, and immunohistochemistry was used to identify sites of local expression. To determine the pathologic significance of increased Wnt, human vascular smooth muscle cells (vSMCs) were treated with Wnt3a, Wnt5a, and Wnt5b recombinant proteins and assessed for changes in cell differentiation and function. RT-PCR and Western blotting showed a significant increase in the expression of Wnt3a, Wnt5a, Wnt5b, and their receptors in diseased coronary arteries compared with that in non-diseased coronary arteries. Immunohistochemistry revealed an abundant expression of Wnt3a and Wnt5b in diseased coronary arteries, which contrasted with little or no signals in normal coronary arteries. Immunostaining of Wnt3a and Wnt5b was found largely in inflammatory cells and myointimal cells. The treatment of vSMCs with Wnt3a, Wnt5a, and Wnt5b resulted in increased vSMC differentiation, migration, calcification, oxidative stress, and impaired cholesterol handling. This study demonstrates the upregulation of three important members of canonical and non-canonical Wnt signaling pathways and their receptors in coronary atherosclerosis and shows an important role for these molecules in plaque development through increased cellular remodeling and impaired cholesterol handling.

Risk Factors for Bone Fractures in Patients With Comorbid Pathology

Patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), leading to macrophage activation, impaired microvascular function, changes in muscle contraction and fibrosis development. In addition, these proinflammatory cytokines promote bone resorption, thereby increasing the incidence of bone fractures. The aim of the study is to evaluate the effect of tumor necrosis factor-alpha receptor types 1 and 2 (TNF-α-SR1 and TNF-α-SR2) on fracture probability in individuals with osteoporosis who have concurrent chronic heart failure (HF) and type 2 diabetes mellitus (T2DM). The study was conducted on 178 women aged 50 to 65 years. Among these women, 48 were in group 1 and had both heart failure and type 2 diabetes. Group 2 included 93 patients with osteoporosis and heart failure and group 3 included 37 women with osteoporosis, heart failure and type 2 diabetes. Thirty-five postmenopausal women without any clinical and instrumental signs of cardiovascular pathology or osteoporosis were selected as the control group. The levels of TNF-α-SR1 and TNF-α-SR2 receptors in patient groups 1-3 were significantly higher (p<0.01) than in the control group, as were their concentrations. In addition, it was found that the levels of both receptors were significantly higher in group 3 than in patients in groups 1 and 2. To evaluate the levels of TNF-α-SR1 and TNF-α-SR2, the data were divided into four quartiles (Q1-Q4) based on the increase in the concentrations of these markers. For TNF-α-SR2, an increasing risk gradient was observed, with the odds ratio (OR) for osteoporosis events increasing from 1.4 to 12.83, but the risk was statistically significant only for Q3-Q4. For Q4 TNF-α-SR1 levels, a significant increase in the risk of an adverse osteoporosis outcome at 36 months was also found (OR=5.25, p=0.038). In addition, the use of loop diuretics was found to be a predictor of high risk of osteoporotic fractures in patients with chronic HF (JR=6.29, 95% CI=1.45-17.26, p=0.015). Postmenopausal women with chronic HF and elevated levels of soluble TNF-α-SR1 and TNF-α-SR2 receptors are at higher risk for osteoporosis and adverse disease progression. In addition, the use of loop diuretics in these individuals is associated with an increased risk of osteoporotic fractures.

RADIOLOGICAL FEATURES OF THE LOCATION OF CYSTIC FORMATIONS IN THE MAXILLARY SINUS AND THEIR RELATIONSHIP WITH ALVEOLAR BONE PATHOLOGY OF THE UPPER JAW

The aim of the study. To study the features of the location of cystic formations in the maxillary sinus based on CT scans and to determine their relationship with the pathology of the upper jaw teeth.
 Materials and methods. The study involved the analysis of 552 head computed tomography scans of patients referred for examination by an otolaryngologist or dentist. The total number of individuals examined was 552, comprising 44.7% females and 55.3% males, aged 18-74 years. The investigation was conducted using the NewTom GO device with a measurement range of 155-172 mGy/cm±10%, with an error of ±4.24%. Statistical processing of data was carried out using the STATISTICA v.12.6 software.
 Results. Out of 552 computed tomography images analyzed, 92 images of individual maxillary sinuses (MS) of 79 patients with single cysts were selected. They were divided into two groups. Group 1 involved patients with cysts on the lower wall of MS (n=76). Group 2 included patients with cysts on other walls (n=16). The assessment of the ratio of 4, 5, 6, 7 tooth roots of the upper jaw to the lower wall of the upper jaw showed that the protrusion frequency in Group 1 was significantly higher (42.1%) compared to Group 2 (18.7%). Meanwhile, the average thickness of the bone over these teeth in Group 2 was significantly greater (3.4 ± 1.09 mm) than in Group 1 (1.9 ± 0.92 mm) (p=0.0003). In both patient groups, the greatest thickness was observed over tooth 4, and the smallest over tooth 7. Additionally, in 33.7% of cases, the cyst was associated with involvement of deep structures of the projecting teeth and the spread of inflammation to the lower wall of MS.
 Conclusions. Among patients referred by an otolaryngologist or dentist for CT examination to radiologically verify pathological processes in the nasal cavity, paranasal sinuses, and the upper jaw teeth, MS cysts were detected in 19.6% of cases, with 83% of them being localized in its lower parts. In patients with cysts located in the lower parts of MS, the roots protruding into the sinus cavity and a thinner layer of bone over them are more frequently observed compared to those where cysts are located in other areas of MS. In patients with cystic formations in the alveolar recess of MS, radiological signs of pathology of the upper jaw teeth are detected in 34% of cases.

Lymphatic malformations: mechanistic insights and evolving therapeutic frontiers.

The lymphatic vascular system is gaining recognition for its multifaceted role and broad pathological significance. Once perceived as a mere conduit for interstitial fluid and immune cell transport, recent research has unveiled its active involvement in critical physiological processes and common diseases, including inflammation, autoimmune diseases, and atherosclerosis. Consequently, abnormal development or functionality of lymphatic vessels can result in serious health complications. Here, we discuss lymphatic malformations (LMs), which are localized lesions that manifest as fluid-filled cysts or extensive infiltrative lymphatic vessel overgrowth, often associated with debilitating, even life-threatening, consequences. Genetic causes of LMs have been uncovered, and several promising drug-based therapies are currently under investigation and will be discussed.

Circular RNA circNCOA3 promotes tumor progression and anti-PD-1 resistance in colorectal cancer.

Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal cancer (CRC) immune escape remains to be elucidated. Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1 (PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream targets of circNCOA3. Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3 expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients. Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells. Moreover, knockdown of circNCOA3 increased the proportion of CD8+ T cells while decreasing the proportion of myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1. Conclusion: Our findings indicate that circNCOA3 might be useful as a potential biomarker to predict the efficacy and prognosis of CRC patients treated with anti-PD-1 therapy.

Frequency of Clinically Significant Findings in the Surgical Pathology Specimen Following Laparoscopic Sleeve Gastrectomy and Concordance with Preoperative Endoscopy: Insights from a Large Single-Center Experience.

Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.

Pathogenetic aspects of the autoreactive form of spontaneous urticaria in adult patients

Objective: to study the parameters of the immune status and the spectrum of autoimmune markers of patients suffering from an autoreactive form of chronic spontaneous urticaria. Materials and methods: the study involved 67 patients with an autoreactive form of chronic spontaneous urticaria, with clinical and laboratory signs of autoimmune pathology, aged 18 to 65 years, who were observed on an outpatient or inpatient basis in the period from 2019 to 2022. Healthy donors without signs of chronic spontaneous urticaria (n=35) were considered as a control group. The results were evaluated according to the dynamics of clinical and functional, immunological examination. Results: when assessing the immune status of patients with autoreactive chronic spontaneous urticaria, a violation of the differentiation processes of immune-competent cells was revealed, with a predominance of T-lymphocytes with helper-inductive activity, entailing an inversion of the immune-regulatory index, activation of the humoral link of the immune system was noted: an increase in B-lymphocytes, immunoglobulins of classes A, M, G, increase of circulating immune complexes. The indicators of total IgE did not differ fundamentally from the level of donors. Changes in the parameters of the monocyte-macrophage link in patients with autoreactive form of chronic spontaneous urticaria indicated an increase in the functional activity of phagocytic cells and depletion of their reserves. Conclusion: in the autoimmune genesis of chronic spontaneous urticaria, there are significant changes in the autoimmune markers corresponding to the concomitant autoimmune disease (rheumatoid factor, antibodies (Ab) to nDNA, Ab to cardiolipin, Ab to β2-glycoprotein, Ab to neutrophils), there is a high percentage of correlation with a positive test result with autologous serum, there are features of immune status of patients with autoreactive form of chronic spontaneous urticaria.