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Introduction：Ischemia reperfusion injury (IRI) is detrimental to kidney transplants and may contribute to poor long-term outcomes of transplantation. Programmed cell death (PCD), a regulated cell death form triggered by IRI, is often indicative of an unfavorable prognosis following transplantation. However, given the intricate pathophysiology of IRI and the considerable variability in clinical conditions during kidney transplantation, the specific patterns of cell death within renal tissues remain ambiguous. Consequently, accurately predicting the outcomes for transplanted kidneys continues to be a formidable challenge. Methods：Eight Gene Expression Omnibus (GEO) datasets of biopsied transplanted kidney samples post IRI and 1548 PCD-related genes derived from 18 PCD patterns were collected in our study. Consensus clustering was performed to identify distinct IRI subtypes based on PCD features (IRI PCD subtypes). Differential enrichment analysis of cell death, metabolic signatures, and immune infiltration across these subtypes was evaluated. Three machine learning algorithms were used to identify PCD patterns related to prognosis. Genes associated with graft loss were screened for each PCD type. A predictive model for graft loss was constructed using 101 combinations of 10 machine learning algorithms. Results：Four IRI subtypes were identified: PCD-A, PCD-B, PCD-C, and PCD-D. PCD-A, characterized by high enrichment of multiple cell death patterns, significant metabolic paralysis, and immune infiltration, showed the poorest prognosis among the four subtypes. While PCD-D involved the least kind of cell death patterns with the features of extensive activation of metabolic pathways and the lowest immune infiltration, correlating with the best prognosis in the four subtypes. Using various machine learning algorithms, 10 cell death patterns and 42 PCD-related genes were identified positively correlated with graft loss. The predictive model demonstrated high sensitivity and specificity, with area under the curve (AUC) values for 0.5-, 1-, 2-, 3-, and 4-year graft survival at 0.888, 0.91, 0.926, 0.923, and 0.923, respectively. Conclusion：Our study explored the comprehensive features of PCD patterns in transplanted kidney samples post IRI. The prediction model shows great promise in forecasting graft loss and could aid in risk stratification in patients following kidney transplantation.

Acute pulmonary embolism (APE) is a life-threatening condition with a high mortality rate. The pathophysiology involves various complex processes. The systemic immune-inflammatory index (SII) is a well-known biomarker that reflects the intricate balance between pro-inflammatory and anti-inflammatory immune components. In this systematic review, we aim to determine the significance of SII as a potential biomarker for APE.

Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives.

In this study, we aimed to compare metabolic risk factors, lipid indices, healthy eating index, and physical activity among premenopausal, menopausal, and postmenopausal women.

Background: Metabolic-associated fatty liver disease and liver fibrosis are intimately linked to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Transient elastography (TE) and point shear wave elastography (pSWE) were used to measure liver stiffness in patients who met the ultrasound criteria for steatotic liver diseases (SLD). This study compared two methods for estimating liver stiffness in patients with SLD, which in turn correlated with liver fibrosis. Method: Ultrasound B-mode imaging was used to identify SLD. In total, 250 MAFLD patients were recruited. Patient characteristics, laboratory investigations, and liver stiffness measurements using TE and pSWE were assessed on the same day.

Background: Polymyalgia rheumatica (PMR) is an inflammatory condition closely linked with giant cell arteritis, which is a large vessel vasculitis. To provide real-world evidence on PMR outcomes and their determinants, we conducted a longitudinal study focusing on symptom relief and acute phase reactant normalization.

The frequency of thyrotoxicosis may vary between countries and some laboratory test results may be used in etiology research. This study aimed to evaluate the prevalence of thyrotoxicosis diagnoses and laboratory test results.

Sepsis is one of the most common causes of death in patients admitted to intensive care units (ICUs). The development of sepsis is significantly influenced by genetic predisposition. In this study, we highlight a potential association between a variant of the fat mass and obesity-associated (FTO) gene and risk of sepsis in children and adolescents.

Research advances in the oncology treatment field have led to the widespread use of immunotherapy. The usage of immune checkpoint inhibitor (ICI) has improved the survival of cancer patients with metastases. This has also led to the rapidly expanding indications for ICI use. However, ICI usage may lead to toxicity, which may be immune-related, in different organ-specific targets. The immune-related adverse events (irAEs) of ICI may lead to increased morbidity, decreased quality of life, and early termination of ICI. The clinical manifestations of irAEs in the gastrointestinal system are variable, ranging from self-limited to life-threatening or fatal events. In this review article, we would like to focus on discussing ICI-induced colitis, which is one of the most common ICI irAEs in the gastrointestinal tract.

Background: Aldosterone synthase (CYP11B2) is crucial for aldosterone production, and variations in its gene may influence type 2 diabetes mellitus (T2DM) development. This study explores the link between two single nucleotide polymorphisms (SNPs) in the CYP11B2 gene - −344T/C and K173R and T2DM in the Moroccan population .

Eosinophilic Esophagitis is a widely-recognized immune-mediated esophagus disease with distinct clinical and histopathological features, exhibiting an increased global incidence. Therapeutic options encompass either dietary measures or pharmacological approaches, including proton pump inhibitors and topical corticosteroids. The use of monoclonal antibodies is currently under comprehensive evaluation, with a plethora of ongoing clinical trials designed to determine their clinical efficacy. The present case report demonstrates an exceptional case of refractory Eosinophilic Esophagitis, unresponsive to conventional treatment, achieving both clinical and histopathological remission subsequent to initiation of benralizumab treatment. Concurrently, our case underscores the necessity for continued research in the field of monoclonal antibodies for their use as a future treatment approach against Eosinophilic Esophagitis.

Objectives: Biomarker-based clinical practice is currently gaining ground and increasingly affects decision making. A variety of biomarkers have been studied through the years and some of them have already an established role in modern medicine, such as procalcitonin (PCT) which has been proposed to reduce antibiotic exposure. We purposed to systematically review all biomarkers examined for guiding the clinical practice in patients with pneumonia.

Background: Respiratory allergies mostly allergic rhinitis and asthma represent an important and increasing public health problem and one of the priorities for the European health systems. There is an increasing public concern regarding the persistence and severity of allergic diseases and many difficulties of health systems in providing prompt specialized medical assistance. Our study aims to highlight the main results of the Alliance 4Life project focused on the evaluation of the burden and management of respiratory allergies in primary care from Romania and comparative health-related data from four Central and Eastern European countries.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represented a disruptive pathology that emerged in late 2019 with profound implications ranging from individual health to health systems and world economy. Our study aimed to evaluate clinical, biochemical and computerized tomography (CT) parameters values in determining the severity of pulmonary embolism (PE) associated with COVID-19.

Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients.

Abstract Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Abstract As childhood obesity rates increase worldwide, the prevalence of obesity-related hypertension is also on the rise. Obesity has been identified as a significant risk factor for hypertension in this age group. National Health Surveys and meta-analyses show increasing trends in obesity and pediatric hypertension in obese children. The diagnosis of hypertension in children involves percentiles relative to age, sex, and height, unlike in adults, where absolute values are considered. Elevated blood pressure (BP) in childhood is consistently associated with cardiovascular disease in adulthood, emphasizing the need for early detection and intervention. The pathogenesis of hypertension in obesity involves multiple factors, including increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system (RAAS), and renal compression due to fat accumulation. Obesity disrupts normal RAAS suppression and contributes to impaired pressure natriuresis and sodium retention, which are critical factors in the development of hypertension. Risk factors for hypertension in obesity include degree, duration, and distribution of obesity, patient age, hormonal changes during puberty, high-sodium diet, sedentary lifestyle, and socioeconomic status. Treatment involves lifestyle changes, with weight loss being crucial to lowering BP. Medications such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may be considered first, and surgical approaches may be an option for severe obesity, requiring tailored antihypertensive medications that consider individual pathophysiology to avoid exacerbating insulin resistance and dyslipidemia.

Abstract Background The triglyceride-glucose (TyG) index is a reliable marker of insulin resistance that is involved in the progression of hypertension. This study aimed to evaluate the association of the TyG index with the risk for major cardiovascular events (MACE) in young adult hypertension. Methods A total of 2,651 hypertensive patients aged 18–40 years were consecutively enrolled in this study. The TyG index was calculated as Ln [triglycerides × fasting plasma glucose/2]. The cutoff value for an elevated TyG index was determined to be 8.43 by receiver-operating characteristic curve analysis. The primary endpoint was MACE, which was a composite of all-cause death, non-fatal myocardial infarction, coronary revascularization, non-fatal stroke, and end-stage renal dysfunction. The secondary endpoints were individual MACE components. Results During the median follow-up time of 2.6 years, an elevated TyG index was associated with markedly increased risk of MACE (adjusted hazard ratio [HR] 3.440, P

The Prostate Imaging Reporting and Data System (PI-RADS) is an essential tool for standardizing the interpretation of multiparametric magnetic resonance imaging (mp-MRI) of the prostate for detecting prostate cancer. This article provides a comprehensive overview of the latest version, PI-RADS 2.1, with clear pictures to guide radiologists in its practical application for improved diagnostic accuracy. The article explores the key modifications, emphasizing the changes in scoring criteria and their impact on clinical decision-making. It discusses the importance of mp-MRI sequences, such as T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging, and clarifies their significance in the PI-RADS 2.1 framework. The article highlights practical insights to help radiologists integrate this updated system into their day-to-day practice, promoting consistency and reliability in reporting.

Chronic liver disease (CLD) has been recently recognized as a major public health priority. Assessment of presence and degree of liver fibrosis is critical to the management of CLD and traditionally required a liver biopsy. However, biopsy has many limitations including the risk of complications and sampling error. Magnetic resonance elastography (MRE) has emerged as a noninvasive and highly accurate technique for evaluating liver fibrosis. In this comprehensive review, we will delve into the current uses and guidelines for the usage of MRE in CLD, highlighting its advantages and limitations.

Solid pseudopapillary tumor is a mixed solid and cystic neoplasm of the pancreas which occurs most commonly in females in second or third decade of life with few reported pediatric cases. It has a low malignancy potential with good prognosis after surgical resection.

The use of Prostate Imaging Reporting and Data System (PI-RADS) with multiparametric magnetic resonance imaging (MRI) has significantly improved the detection of clinically significant prostate cancer (csPCa), but there are certain challenges that the reader may face. This review provides an overview of the pitfalls associated with the PI-RADS system for multiparametric prostate MRI (mpMRI), with suggestions/pearls to help overcome these pitfalls.

Prostate cancer remains a significant global health concern, necessitating continuous research and innovation in treatment modalities. This review explores the currently employed techniques in radiation dose planning and tumor irradiation in the context of prostate cancer management. In addition, we delve into the nuances of expected posttreatment magnetic resonance imaging (MRI) appearances within the gland or in the prostate bed, postradiation tumor recurrence, and its mimics.

For a long time, the family of receptor tyrosine kinases, including epidermal growth factor receptor and insulin-like growth factor 1 receptor, was regarded as the main players stimulating cell proliferative signaling. Today, it is increasingly clear that many G protein-coupled receptors (GPCRs) are also involved in controlling the hallmarks of cancer by activating diverse intracellular signaling networks. GPCRs can therefore be considered as promising drug targets for fighting against diverse types of human malignancies. Although plant polyphenols, flavonoids, are well known for their diverse anticancer effects inhibiting the growth, proliferation, migration, and invasion of malignant cells, involvement of GPCRs in these activities has still remained largely unelucidated. Therefore, in this review article, the current knowledge about the role of GPCRs in anticancer action of structurally varied flavonoids is compiled, highlighting the ability of these natural polyphenols to modulate the expression levels of GPCRs but also suppress the action of endogenous ligands and downstream tumor-promoting events. These data show that targeting the respective GPCRs by specific flavonoids may open new perspectives in the therapeutic intervention in human malignancies.

Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.

Background: The European Glaucoma Society recommends that selective laser trabeculoplasty (SLT) be considered as a first-line treatment option for patients with mild or moderate primary open-angle glaucoma (POAG) or for those who have not responded well to medications. Purpose: To assess the efficacy of POAG treatment with SLT based on examination of the function of Schlemm’s canal (SC) Methods: This paper presents the results of clinical studies and one-month dynamic follow-up of 38 POAG patients (52 eyes) who underwent SLT with a Tango Reflex YAG/SLT laser (Ellex, USA) at the VISUS clinic (Zaporizhzia). Of the 38 patients, 18 (47.37%) were males and 20 (52.63%) females. Patient age ranged from 58 to 85 years (mean age ± standard deviation, 69 ± 9.9 years). Results: There was a significant difference in the response to SLT between eyes with a functional blockage and those with an organic blockage of SC. In the former eyes, true intraocular pressure (P0) decreased from 25.66 ± 0.41 mmHg before SLT to 19.2 ± 0.24 mmHg, outflow facility coefficient increased by 40%, and Becker’s coefficient decreased by 46.63% at 1 month after SLT (p < 0.05). In eyes with an organic blockage of SC, P0 changed from 27.69 ± 0.51 mmHg before SLT to 27.64 ± 0.49 mmHg at 1 week, and even increased to 28.75 ± 0.52 mmHg at month 1 after SLT (p ˃ 0.05), and tonography characteristics did not change. Conclusion: The current study demonstrated that the success rate of SLT in eyes with POAG was 69.2%. The success rate, however, may reach 100% (with a mean percentage IOP reduction of 25.18%, 40 percent increase in the outflow facility coefficient, and 46.63 percent decrease in the Becker’s coefficient) if SLT is performed only in POAG eyes with a functional blockage of SC. If established, the functional state of SC may be used for determining indications and contraindications for SLT in POAG.

Introduction. Combined drug treatment of primary open-angle glaucoma (POAG) with several types of antihypertensive drops from different pharmacological groups is performed to enhance the hypotensive effect in cases when monotherapy does not always reduce intraocular pressure (IOP) to a tolerance level. Рurpose. Evaluation of the effectiveness and tolerability of a fixed combination antihypertensive drug, Glaubrinza, in the treatment of patients with POAG. Methods. Depending on the treatment, 2 groups of patients were formed. The main group included 30 patients (60 eyes), who instilled the drug Glaubrinza, 1 drop 2 times a day. The comparison group consisted of 30 patients (60 eyes), whom the drug Simbrinza was instilled according to the same scheme as the drug Glaubrinza. All patients underwent a general ophthalmological examination and special research methods, including: computer static perimetry, pachymetry, and optical coherence tomography (OCT). The local and general tolerability of the drug was assessed within 10 days using a standard scale. Results. The effectiveness of the treatment in the main group was assessed as high in 85% and moderately high in 15% and averaged 3.8±0.1 points. The effectiveness of treatment in the comparison group was assessed as moderately high in 20% and high in 80% of patients and averaged 3.8±0.03 points. Conclusions. Glaubrinza is a highly effective drug for treating POAG and is not inferior in all studied parameters to the reference drug and is also economically accessible to all segments of the population.

Purpose. To assess and evaluate cytological changes of conjunctival epithelial cells collected by CIC and relative expression of CD15 before and after 2-month treatment with sodium hyaluronate 0.2% and 0.001% hydrocortisone among patients with dysregulatory inflammatory changes of the conjunctiva in type 2 diabetes mellitus. Methods. We prospectively enrolled 38 T2DM patients (76 eyes). All patients were further divided into two groups: Group I - study group (n=23; 46 eyes); Group II - controls (n=15; 30 eyes). Group I received one drop of sodium hyaluronate 0.2% and 0.001% hydrocortisone (HA/Hydrocortisone); group II – one drop of sodium hyaluronate two times daily for two months, respectively. Results. Relative expression of epithelial CD15 was significantly reduced after the treatment in Group I (p˂0,001) in contrast to Group II (p=0,8726). Absence of CD 15 expression was found in five cases (11%) before treatment and seven cases (15%) after HA/Hydrocortisone administration (p=0,7582). Macrophage infiltration was observed in 28% of participants upon baseline examination and it completely disappeared after treatment with HA/Hydrocortisone. These findings show that HA/hydrocortisone drops should be considered as an effective treatment for patients with dysregulated parainflammation of the conjunctiva. Conclusions. Treatment with hyaluronate/hydrocortisone eye drops showed a statistically significant improvement of conjunctival cytology and functional tests: lipid layer thickness (LLT), tear breakup time (TBUT), meibomian gland loss (MGL) along with reduction of relative expression of epithelial CD15 among T2DM patients.

Purpose. To demonstrate the effectiveness of combined surgery including calcific band keratopathy (CBK) treatment followed by cataract extraction with intraocular lens (IOL) implantation in pediatric patients, assessed through preoperative and postoperative best-corrected visual acuity (BCVA) and changes in corneal transparency. Methods. This retrospective study was conducted on the medical records of patients treated for CBK combined with cataract secondary to chronic uveitis between January 2018 and December 2020. The study included 15 eyes of 14 pediatric patients. Clinical parameters recorded included age, primary diagnosis, and preoperative and postoperative BCVA using a Tumbling E chart. Postoperative data were collected at 3 days, 6 months, and 12 months after surgery. Results. Preoperative BCVA averaged 2.03 ± 0.69. On the 3rd postoperative day, BCVA improved to 0.82 ± 0.39, with further improvements to 0.78 ± 0.43 at 6 months and 0.69 ± 0.45 at 12 months. The mean BCVA increased by 2 lines, and BCVA improved by 6 lines within one year postoperatively. Recurrence of CBK was observed in 3 eyes (20%) at 6-month follow-up. Conclusion. Simultaneous EDTA chelation of calcium plaques and phacoaspiration with IOL implantation is an effective and safe treatment for CBK combined with cataract in pediatric patients. This combined approach resulted in significant improvements in visual acuity and corneal transparency and symptomatic relief. However, the high recurrence rate indicates the need for further research.

Background: Hyperhomocysteinemia determined by polymorphisms of genes encoding folate cycle enzymes is closely correlated with markers of systemic inflammation. Prolonged excessive cytokine production in the neural tissue in patients with type 2 diabetes mellitus (T2DM) causes gliosis, posing a threat of neuroinflammation, a potential pathogenetic component of diabetic retinopathy (DR). Purpose: To assess plasma levels of neuroinflammation markers (IL-1β and IL-10) and gliosis marker, non-neuronal enolase (NNE), in T2DM patients with DR and genetically determined hyperhomocysteinemia. Methods: One hundred and six T2DM patients with DR were involved in the study. DR severity was classified according to ETDRS DR severity system (DRSS) as non-proliferatve (NPDR; DRSS level 47–53), proliferative (NPDR; DRSS level 47–53) and advanced (APDR; DRSS level 81-85). The control group was composed of 64 individuals. Cases and controls were comparable for age, sex and way of life. MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), and MTR A2756G (rs1805087) genotypes were determined using the TaqMan® SNP Genotyping Assay (Applied Biosystems, Foster City, CA) and the ABI 7500 real-time PCR system (Applied Biosystem). Enzyme-linked immunosorbent assay (ELISA) kits were used to assess plasma levels of L-homocystein, cytokines and NNE. Results: Plasma IL-1β levels were 1.7 times higher in patients with diabetes duration shorter than 15 years compared to those with longer diabetes duration. In addition, plasma NNE levels were higher in the former patients, but the difference was not significant. There was correlation of plasma L-homocystein levels with plasma IL-10 (R = 0.357, p < 0.01), IL-1b (R = 0.320, p < 0.01) and NNE (R = 0.286, p < 0.01) levels. Plasma NNE levels correlated with plasma IL-10 (R = 0.279, p < 0.01) and IL-1beta (R = 0.368, p < 0.01). Conclusion: Elevated plasma levels of pro-inflammatory cytokines in patients indicate an important role of neuroinflammation in the pathogenesis of DR. The rs1801131 CC, rs1805087 GG and rs1801131 CC genotypes may be considered risk factors for the development of DR in patients with T2DM.

Purpose: To establish prognostic biomarkers of non-prolefarative diabetic retinopathy (NPDR) progression in T2DM on the basis of examination of clinical, ophthalmological and laboratory (carbohydrate and lipid metabolism and coagulation and hemostasis) characteristics. Methods: This study included 358 T2DM2 patients with diabetic retinopathy (DR); for each patient, the eye with more severe DR was included in the study. Cases were dichotomized into three groups based on DR severity: group 1 (NPDR; 189 eyes), group 2 (preproliferative DR or PPDR; 96 eyes), and group 3 (proliferative DR or PDR; 73 eyes). Central retinal thickness (CRT; µm) and central retinal volume (CRV) were assessed by optical coherence tomography (OCT; mm3). Serum samples were taken to assess fasting serum glucose, glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, and fibrinogen. Coagulation and hemostasis parameters were assessed. Statistical analyses were performed with EZR version 1.54. Results: Associations of the variables with the risk of NPDR progression were confirmed by a univariate logistic regression analysis. The area under curve (AUC) was largest for HbA1c (AUC = 0.84), followed by CRT and CRV (AUC = 0.79). In addition, the AUC ranged from 0.56 to 0.67 for the rest of variables. Age, gender, diabetes duration, and blood HDL level were not associated with NPDR progression. Our multivatiate logistic regression analysis found six biomarkers (age, HbA1c, LDL, VLDL, prothrombin index and CRT) directly associated with the risk of NPDR progression (AUC = 0.91; p < 0.001). The established association was mostly due to the three independent variables, HbA1c, VLDL and CRT (AUC = 0.90; p < 0.001). Conclusion: Independent effects on the risk of NPDR progression were confirmed for HbA1c, VLDL and CRT. The built model was found to be of very high predictive quality, which allowed recommending it for confirming high risk for NPDR progression in equivocal clinical cases or as a criterion for conclusive prognosis in the relevant expert systems.

Purpose. The purpose of this research was to measure lens posterior cortex thickness and compare it between Chornobyl ex-clean-up workers and healthy individuals to determine whether Chornobyl ex-clean-up workers have a higher prevalence of posterior cortex cataract. Methods. The study was conducted on 32 eyes of healthy, non-exposed individuals, 32 eyes of individuals who worked only in Chornobyl City, and 16 eyes of individuals who worked on the roof of the reactor. All measurements were performed using a Heidelberg Anterion device. Statistical analyses were performed using Jamovi statistical software. Results. The results showed that those who had worked on the roof of the reactor had a significantly higher percentage of their lens occupied by the posterior cortex (median 17.3%, IQR 15.5–18.5%) compared to both the controls and city workers. Therefore, they also have a higher prevalence of posterior subcapsular cataracts (p

Purpose: To evaluate 12-month clinical outcomes of a treat-and-extend regimen with intravitreal aflibercept injections in patients with occult (type 1) choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSC). Methods: This was a prospective observational single-center study involving 24 patients (24 eyes) with occult (type 1) CNV secondary to chronic CSC. All patients received three initial loading doses of intravitreal 2 mg (0.05 ml) aflibercept at 4-weekly intervals, followed by a treat-and-extend protocol. The primary outcome was best-corrected visual acuity (BCVA) at 12 months. Statistical analyses were conducted and graphs were created using Statistica 10.0 software. Results: Mean BCVA increased significantly from 0.44 ± 0.35 at baseline to 0.58 ± 0.3 at month 12 (р = 0.01). At month 12, complete resolution of SRF was observed in 18 eyes (75%). The mean number of intravitreal aflibercept injections over 12 months was 7.5 ± 1.4. Conclusion: Treat-and-extend intravitreal aflibercept is an effective and safe approach for managing patients with occult (type 1) CNV secondary to chronic CSC.

This paper reviews the current insights into, and prospects for better understanding of, the pathogenesis of optic nerve edema or swelling in the presence of inflammatory or ischemic optic neuropathy. Forty-six Ukrainian and foreign publications on the subject were reviewed and considered. There are several theories of optic nerve damage due to swelling (edema); these include biomechanical theories (features of structural components, a change in the optic nerve architecture, and stretching of the Bruch membrane) and an ischemic theory (abnormal perfusion and axonal transport stasis). Of importance are also abnormal vascular permeability and exudation of plasma and blood cells, which results in accumulation of fluid, inflammatory mediators and metabolic products between peripapillary retinal layers, impeding the outflow and metabolism in the posterior segment of the eye. Current neuroimaging techniques (optical coherence tomography (OCT) and OCT angiography) facilitate improved understanding of structural changes in the optic nerve head. Therefore, studies on optic disc architecture, fluid circulation in the posterior segment, and interaction of optic nerve head components in optic nerve edema or swelling will facilitate (a) improved understanding of the pathogenesis and (b) the differential diagnosis of acute optic neuropathies, and, consequently, will enable treatment for inflammatory and ischemic optic nerve lesions.

The incidence of blindness due to exudative retinal diseases reduced significantly over the twenty years of the use of anti-vascular endothelial growth factor (VEGF) therapy in ophthalmology. However, despite advances in recent years, current outcomes of anti-VEGF therapy for exudative retinal diseases are not always optimal. This review aims to highlight the advances in the development of VEGF inhibitors and identify potential ways of improving the outcomes of anti-VEGF therapy for, and solving current problems in the management of, exudative retinal diseases.

We report a lethal case of a female patient who has not undergone surgery for her giant invasive infrasellar/endosellar/suprasellar/parasellar/retrosellar pituitary adenoma. The paper presents results of histological examination of optic nerves and considers the mechanisms of vision loss in prolonged chiasmal and optic nerve compression.

Abstract Introduction Acute kidney injury (AKI) is frequently seen in critically ill patients and is associated with high mortality and morbidity. However, the optimal dialysis modality in such patients remains controversial. We examined the hemodynamic tolerability of hemodialysis modalities in critically ill individuals with AKI. Methodology Critically ill patients with AKI who underwent Continuous Renal Replacement Therapy (CRRT), Sustained Low-Efficiency Diafiltration (SLEDD-f), or Sustained Low-Efficiency Dialysis (SLED) dialysis were included in the study. In-hospital mortality, number of dialysis sessions, number of sessions terminated pre-maturely, change in blood pressure during dialysis, and hemodynamic instability during dialysis sessions were noted. Results A total of 264 patients were included, of which 78 received Continuous Renal Replacement Therapy (CRRT), 62 received Sustained Low-Efficiency Diafiltration (SLEDD-f), and 124 received Sustained Low-Efficiency Dialysis (SLED), with a total of 682 sessions among 264 patients. The commonest cause for AKI was septic shock (32.6%, n=43). All CRRT and SLEDD-f sessions were delivered without anticoagulation, and SLED was delivered without anticoagulation in 88.7% of sessions. There was a significant decrease in mean arterial pressure in CRRT compared to other modalities, with higher mortality. However, patients undergoing CRRT were more sicker. There was no significant difference between SLEDD-f and SLED in terms of outcomes. Conclusion SLEDD-f and SLED have good hemodynamic tolerability compared to CRRT. There was no significant difference in hemodynamic disturbances between SLEDD-f and SLED despite a higher proportion of patients on SLEDD-f being more critical.

Abstract Background There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). Methods 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. Results In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). Conclusions The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.

Abstract Background Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN. Methods We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes. Results Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN. Conclusion This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN.

Abstract Background Kagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS. Case presentation The woman’s two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS. Conclusions Given the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

One of the directions in treatment of chemoresistant breast cancer (BC) may include new methods of activating the immune response against tumor cells. Clinically used checkpoint inhibition using antibodies to PD-1 and PD-L1 works in some patients, but the lack of biomarkers means number of respondents is low. The possibility of combining this method with chemotherapy is limited by an increased risk of toxic liver damage, development of immune-related pneumonitis, and thyroid dysfunction. This article includes introduction into the clinic of new methods of immunotherapy for BC, among which epigenetic activation of retroelements, double-stranded transcripts of which stimulate the interferon response against the tumor, is promising. For this purpose, inhibitors of DNA methyltransferase*, histone deacetylase* and histone methyltransferase* are used (* subtitles in the main text). Their antitumor effect is also mediated by removal of repressive epigenetic marks from tumor suppressor genes. However, numerous studies have proven the role of retroelements in the carcinogenesis of various malignant neoplasms, including BC. Moreover, endogenous retroviruses HERV-K and LINE1 retrotransposons are planned to be used as diagnostic biomarkers for BC. Therefore, a rational approach to using viral mimicry in antitumor therapy of BC may be the simultaneous suppression of specific retrotransposons (drivers for carcinogenesis) using reverse transcriptase inhibitors and silencing of specific transposons involved in carcinogenesis using complementary microRNAs. To determine possible pathways of influence in this direction, 35 specific transposon-derived microRNAs* changes in BC were identified, which can become guides for targeted therapy of BC.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognostics and substantial therapeutic challenges, with dismal survival rates. Tumor resistance in PDAC is primarily attributed to its fibrotic, hypoxic, and immune-suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), an Food and Drug Administration (FDA)-approved minimally invasive technique for treating pancreatic cancer, disrupts tumors with heat and induces coagulative necrosis, releasing tumor antigens that may trigger a systemic immune response—the abscopal effect. We aim to elucidate the roles of EUS-RFA-mediated thermal and mechanical stress in enhancing anti-tumor immunity in PDAC. A comprehensive literature review focused on radiofrequency immunomodulation and immunotherapy in pancreatic tumors to understand the pathophysiological mechanisms of RFA and its effect on the TME, which could prevent recurrence and resistance. We reviewed clinical, preclinical, and in vitro studies on RFA mechanisms in pancreatic adenocarcinoma, discussing the unique immunomodulatory effects of EUS-RFA. Recent findings suggest that combining RFA with immune adjuvants enhances responses in pancreatic adenocarcinoma. EUS-RFA offers a dual benefit against PDAC by directly reducing tumor viability and indirectly enhancing anti-tumor immunity. Observations of neutrophil-mediated immunomodulation and programmed cell death ligand 1 (PD-L1) modulation support integrating EUS-RFA with targeted immunotherapies for managing pancreatic adenocarcinoma. Integrating EUS-RFA in PDAC treatment promises direct cytoreduction and synergistic effects with molecular targeted therapies. Prospective clinical trials are crucial to assess the efficacy of this combined approach in improving outcomes and survival rates in advanced PDAC cases.

The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche. In fact, they share many signals that are responsible for interactions between LSCs and the bone marrow niche, due to several biological similarities between LSCs and HSCs. On the other hand, LSCs differ from HSCs in their abnormal activation of important signaling pathways that regulate survival, proliferation, drug resistance, invasion, and spread. Targeting these altered niches can help in better treatment choices for hematological malignancies and bone marrow disorders in general and acute myeloid leukemia (AML) in particular. Moreover, targeting those niches may help in decreasing the emergence of drug resistance and lower the relapse rate. In this article, the authors reviewed the most recent literature on bone marrow niches and their relations with either normal HSCs and AML cells/LSC, by focusing on pathogenetic and therapeutic implications.

Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further necessitate the exploration of alternative therapies. Anticancer peptides (ACPs) offer promising potential as cancer-fighting agents and address challenges such as treatment resistance, tumor heterogeneity, and metastasis. Although these peptides exist as components of the defense system in various plants, animals, fungi, etc., but can also be created synthetically and used as a new treatment measure. These peptides possess properties that make them appealing for cancer therapy, such as apoptosis induction, inhibition of angiogenesis, and cell membrane breakdown with low toxicity. Their capacity to specifically target cancer cells selectively holds promise for enhancing treatment environments as well as improving patients’ quality of life. This review provides detailed insights into the different prospects of ACPs, including their characterization, use as immunomodulatory agents in cancer treatment, and their mechanistic details after addressing various immunological challenges in existing cancer treatment strategies. In conclusion, ACPs have promising potential as novel cancer therapeutics due to their target specificity and fewer side effects than conventional therapies.

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.

Aim: Human epidermal growth factor receptor-2 (HER2) is a well-established prognostic and predictive biomarker. It is an FDA-approved therapeutic target for HER2 positive breast, gastroesophageal, and more recently, lung and colon cancers. It is an emerging biomarker in biliary tract, bladder, cervical, endometrial, ovarian, and pancreatic cancers. The emergence of new indications warrants further characterization of HER2 expression in diverse cancer populations. This study investigated HER2 expression in solid tumour samples and the feasibility of obtaining these results. Methods: Prospective consent was obtained at a Canadian tertiary academic cancer center from adult oncology patients who were referred for molecular genetic testing of malignant tissue samples. Standard HER2-targeted malignancies were considered breast and gastroesophageal, and were excluded from this study. Between July 2020 and November 2023, 499 samples of solid tumors underwent immunohistochemistry (IHC) HER2 staining. A median turnaround time (TAT) of 14 days would be considered feasible for clinical decision making. Results: The mean age (± SD) of participants was 67 ± 12.5 years, with 270 (54%) male and 229 (46%) female. HER2 protein expression was measured in 42 unique cancer types. IHC levels of 0, 1+, 2+, and 3+ were reported and were 43%, 12%, 35%, and 10% of all analyzable samples respectively (tissue inadequate in 3% of samples). The median TAT for HER2 expression results from time of request to result in release was 18 (interquartile range, 11 to 30) days. Conclusions: HER2 protein expression varies widely between different cancer types. TAT for HER2 IHC results was a median of 18 days, which is close to our feasibility cut-off.

Objective: To evaluate and characterize the cognitive changes in COVID-19 participants at 6-month follow-up, and to explore a possible association with clinical symptoms, emotional disturbance and disease severity. Methods: This single-center longitudinal cohort study included participants aged 20 and 60 years old to exclude cognitive impairment age-associated with confirmed COVID-19 infection. The initial evaluation occurred 10 to 30 days after hospital or ambulatory discharge, with a subsequent follow-up at 6 months. Patients who had a history of cognitive impairment, neurological conditions, or serious psychiatric disorders were not included. Information on demographics and laboratory results was gathered from medical records. Cognitive outcomes were assessed with a neuropsychological battery including attention, verbal and visual memory, language and executive function tests. Results: A total of 200 participants were included in the study, and 108 completed the follow-up visit. At the 6-month follow-up, comparing the means from baseline with those of the follow-up evaluation, significant overall improvement was observed in verbal and visual memory subtests (p = 0.001), processing speed (p = 0.001), executive function (p = 0.028; p = 0.016) and naming (p = 0.001), independently of disease severity and cognitive complaints. Anxiety and depression were significantly higher in groups with Subjective Cognitive Complaints (SCC) compared to those without (p < 0.01 for both). Conclusions: Persistent symptoms are common regardless of disease severity and are often linked to cognitive complaints. Six months after COVID-19, the most frequently reported symptoms included headache, dyspnea, fatigue, cognitive complaints, anxiety, and depression. No cognitive impairment was found to be associated with the severity of COVID-19. Overall, neuropsychological and psychopathological improvement was observed at 6 months regardless of disease severity and cognitive complaints.

There are approximately 2.5 million cases of traumatic brain injury (TBI) in the U.S. each year. Post-traumatic epilepsy (PTE), a sequela of TBI, has been shown to occur in approximately 15% of TBI patients. Pre-disposing risk factors for the development of PTE include severe TBI and penetrating head injury. PTE is associated with poor functional outcomes, increased negative social factors, and mental illness. We conducted a retrospective chart review with a 5-year timeframe at an urban Level 1 Trauma Center. Patients with ICD-10-CM codes associated with TBI were identified. Patients were coded as TBI with or without PTE by the presence of codes associated with PTE. Datapoints collected included risk factors for PTE and encounters with neurologists. A total of 1886 TBI patients were identified, with 178 (9.44%) classified as TBI with PTE. The most significant risk factor associated with PTE was severe brain injury, with an odds ratio (OR) of 2.955 (95% CI [2.062,4.236]; p < 0.0001). Only 19 of 178 patients (10.7%) visited a neurologist beyond 6 months after TBI. Our results suggest the presence of a significant population of patients with PTE and the need for better follow-up.

Moyamoya disease is a cerebrovascular pathology characterized by progressive stenosis of the internal carotid arteries and their branches, leading to ischemic and/or hemorrhagic disorders of the cerebral circulation, primarily affecting children and young adults. We present a case of a 23-year-old woman with a history of recurrent cerebrovascular accidents since childhood. Despite experiencing focal motor seizures and transient ischemic attacks, her condition remained undiagnosed until 2006, when, at the age of 7, a digital subtraction angiography revealed characteristic bilateral internal carotid artery occlusions. Subsequent diagnostic challenges and treatments preceded a worsening of symptoms in adulthood, including generalized tonic–clonic seizures. Upon presentation to our clinic, the patient exhibited upper motor neuron syndrome and occipital lobe syndrome, consistent with the disease’s pathophysiology, neuroimaging, and clinical manifestations. Imaging studies confirmed multiple ischemic lesions throughout the cerebral vasculature. Treatment adjustments were made due to the increased incidence of seizures, and the dose of her anti-seizure medication—divalproex sodium—was increased. This case underscores the diagnostic complexities and challenges in managing moyamoya disease, emphasizing the importance of early recognition and prompt intervention.

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013–2022). Epilepsy and DRE prevalence and incidence in children