Exploring vasculogenesis in the normal human kidney and clear cell renal cell carcinoma: insights from development to tumor progression and biomarkers for therapy response.

Vasculogenesis, which refers to the development of blood vessels from precursor cells, is a process that occurs predominantly during early embryonic life. It plays a crucial role in the establishment of the primitive vascular network. Vasculogenesis diminishes throughout the fetal vascular remodeling process, giving way to angiogenesis, which becomes the predominant mechanism after birth. At first, the development of the kidney's blood vessels depends on vasculogenesis, and then both vasculogenesis and angiogenesis happen simultaneously. Both processes are necessary for the normal development of the renal vasculature. Although the kidneys are highly vascularized, our understanding of normal kidney vasculogenesis is still incomplete. This lack of knowledge may explain the limited data available on the role of vasculogenesis in the progression and spread of renal cancers. In other types of cancer, researchers have well documented the phenomenon of tumor vasculogenesis. However, there is currently limited and fragmented information about the occurrence of clear-cell renal cell carcinomas (cc-RCC). In this article, we provide a comprehensive review of the current understanding of normal kidney vasculogenesis and vasculogenic pathways in clear cell renal cell carcinoma (cc-RCC). We specifically focus on cellular precursors, growth factors, and the influence of the normal and tumor environments on these processes. It will carefully look at how tumor vasculogenesis might affect the growth and metastasis of clear cell renal cell carcinoma (cc-RCC), as well as how it might affect the effectiveness of drugs and the development of therapy resistance.

Retrospective Analysis of Vitamin D Deficiency in an Adult Population of Arad County, Western Romania (2019-2022).

Vitamin D, a steroid hormone synthesized primarily in the skin upon exposure to ultraviolet light, is widely deficient across global populations. This study aimed to fill the data gap in Western Romania by measuring 25-hydroxy-vitamin D levels in a cohort of 7141 from Arad County. It was observed that women, younger adults (18-29 years), and older adults (70-79 years) had notably lower vitamin D levels compared to the average population. Additionally, there was a rise in vitamin D levels over the four-year span of 2018-2022, coinciding with the COVID-19 pandemic. Our research provides fresh data on those most susceptible to vitamin D deficiency and lays the groundwork for educational campaigns on vitamin D supplementation benefits.

Lipid Profile Paradox: Investigating Improved Lipid Levels in Diabetic Mellitus Patients with Foot Ulcer Infections-A Prospective Descriptive Study.

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder posing multifaceted challenges to global public health. Among its numerous complications, infected diabetic foot ulcers (IDFUs) represent a particularly debilitating consequence. Beyond cardiovascular implications, there is an emerging understanding of the interconnectedness among IDFUs, neuropathy, atherosclerosis, and dyslipidemia. IDFUs, peripheral neuropathy, and atherosclerosis share common risk factors and mechanistic pathways. The primary objective of this study was to characterize the lipid profiles in DM patients with IDFUs, comparing them with DM patients without foot ulcers, and with a control group of healthy subjects. The secondary objectives included evaluating apolipoprotein E (ApoE) levels across these study groups and comparing lipid profiles within IDFU subgroups. A total of 160 patients were assessed for this study. After applying exclusion criteria, 140 participants were included, divided into three groups: Group IDFU (80 patients with IDFUs), Group DM (32 patients with DM but no foot ulcers), and Group Controls (28 healthy controls). Compared to Group DM, Group IDFU demonstrated lower levels of high-density lipoprotein cholesterol (HDL-C) (30.9 ± 12.6 mg/dL vs. 40.8 ± 16.6 mg/dL, p = 0.002), but improved levels of ApoE (160.9 ± 68.4 mg/dL vs. 197.2 ± 69.6 mg/dL, p = 0.01), triglycerides (TG) (126.9 ± 56.2 mg/dL vs. 165.8 ± 79.0 mg/dL, p = 0.004), low-density lipoprotein cholesterol (LDL-C) (84.2 ± 32.3 mg/dL vs. 92.3 ± 39.3 mg/dL, p = 0.1), and total cholesterol (133.6 ± 43 mg/dL vs. 164.6 ± 44.4 mg/dL, p = 0.002). The IDFU patients exhibit improved lipid profiles, excepting HDL-C, which is unusual because IDFU follows complications related to dyslipidemia for DM patients. Anemia, impaired renal function, and elevated TG levels were identified as biomarkers for mortality among patients with IDFUs. The data suggest that a lower level of HDL-C and an improved lipid profile may indicate a systemic end-stage disease manifestation in DM patients with IDFUs.

Cystic Echinococcosis in Hospitalized Adult Patients from Western Romania: 2007-2022.

Cystic echinococcosis (CE) is a neglected parasitic disease caused by the tapeworm Echinococcus granulosus. The aim of this study was to assess the epidemiological features of human cystic echinococcosis in patients from Western Romania. We retrospectively investigated the medical records of patients hospitalized with CE between 1 January 2007 and 1 September 2022. A total of 366 patients (range 18-90 years) were recorded. The number of hospitalized individuals was higher in patients aged 50-59 years (83/366, 22.7%), in females (194/366, 53%), and in residents of rural areas (225/366, 61.5%). The liver was the most common localization of the cysts (302/366, 82.5%). Ninety-eight patients (26.8%) presented complications, including biliary fistula, allergies, and infection of the cyst. Patients with complications had a longer mean hospital stay (15.7 ± 8.3 days) compared to patients without complications (11.5 ± 7.3 days) (p < 0.001). The results of this study revealed that patients diagnosed with CE required hospitalization and extended medical care, indicating that this zoonotic disease remains a significant public health problem in Western Romania. Public health authorities should enhance CE surveillance by implementing control programs and mandatory notification of new cases.

The importance of CA 72-4 and CA 19-9 dosing in gastric cancer.

Serological analysis of tumor markers has emerged as a non-invasive method for monitoring cancer patients, including tumor recurrence and response to treatment. Tumor markers have the potential to aid in both the diagnosis and prognosis of cancer, but their most important role currently lies in the monitoring of tumor progression. Tumor markers can also provide valuable information on treatment effectiveness, with changes in plasma values indicating tumor regression or progression. This research aimed to investigate the correlation between the serum detection values of three tumor markers - CEA, CA 19-9, and CA 72-4 - and their utility in the diagnosis and prognosis of patients with gastric cancer. The study seeks to uncover the relationship between these tumor markers and the evolution of gastric cancer, providing insights into their potential use in clinical practice.

Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview.

In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.

First Case of Raoultella planticola Urinary Tract Infection Reported in Western Romania.

Raoultella planticola is a Gram-negative bacterium rarely involved in urinary tract infections. The patient was an 80-year-old woman with several associated diseases who presented to the hospital with fever and dysuria. Raoultella planticola was identified to be the causative agent of the urinary tract infection. Antibacterial treatment led to a full recovery within 7 days. This report highlights the presence of a rare pathogen as a causative agent in the case of a urinary tract infection and also the importance of using multiple methods in order to identify bacteria and to establish the diagnosis.

The Mutually Mediated Chloride Intracellular Channel Protein 1 (CLIC1) Relationship between Malignant Cells and Tumor Blood Vessel Endothelium Exhibits a Significant Impact on Tumor Angiogenesis, Progression, and Metastasis in Clear Cell Renal Cell Carcinoma (ccRCC).

Background: Overexpression of chloride intracellular channel protein 1 (CLIC1) in tumor cells has been confirmed, but it has received less attention in the tumor blood vessel endothelium. Aim: The assessment of CLIC1 expression in ccRCC tumor blood vessels and its relationship with TNM parameters and tumor cell CLIC1 expression. Methods: CLIC1 immunostaining in ccRCC was evaluated in 50 cases in both malignant cells and tumor blood vessels (CLIC1 microvessel density-CLIC1-MVD) and was correlated with TNM staging parameters. Results: CLIC1-MVD was observed in approximately 65% of cases, and CLIC1 co-localization in both tumor and endothelial cells was observed in 59% of cases. ccRCC was classified into four groups (Classes 0−3) based on the percentage of positive tumor cells, with each group including sub-groups defined by CLIC1 expression in the endothelium. Class 3 (60−100% positive tumor cells) had the highest CLIC1-MVD, with an impact on T and M parameters (p value = 0.007 for T, and p value = 0.006 for M). For cases with CLIC1 intracellular translocation, there was a strong correlation between CLIC1-MVD and M (p value < 0.001). Conclusions: Co-expression of ccRCC tumor and endothelial cells promotes tumor progression and metastasis and should be investigated further as a potential therapeutic target for ccRCC and other human malignancies.

Screening for the Detection of Toxoplasma gondii IgG, IgM and IgA in Females of Reproductive Age from Western Romania.

Toxoplasma gondii, a zoonotic protozoan parasite, has the capacity to infect the fetus if the pregnant woman primarily acquires the infection during pregnancy. We evaluated the prevalence of T. gondii IgG, IgM and IgA antibodies in women of reproductive age residing in Western Romania. We also assessed the value of adding a T. gondii IgA test to the serologic panel for the diagnosis of toxoplasmosis, including the detection of a recently acquired infection. Serologic testing to demonstrate the presence of T. gondii IgG antibodies was conducted in 1317 females aged 15−45 years. T. gondii IgM and IgA antibody tests were performed in those with detectable IgG antibodies and IgG avidity test was performed if IgM and/or IgA screening test results were positive. T. gondii IgG were detected in 607 (46.09%; 95%CI: 43.41−48.79) of 1317 study participants and IgG seroprevalence tended to increase with age from 35.44% (95%CI: 29.89−41.30) in age group 15−24 years to 62.85% (95%CI: 56.57−68.82) in age group 35−45 years, showing a significant age-associated increase (p < 0.001). Of the 607 persons with detectable T. gondii IgG antibodies, T. gondii IgM antibodies were demonstrated in 8.90% (95%CI: 6.88−11.43), T. gondii IgA in 1.65% (95%CI: 0.90−3.01) and both T. gondii IgM and IgA in 0.99% (95%CI: 0.45−2.14). The prevalence of IgA antibodies tended to decrease with increasing avidity, from 75% (95%CI: 19.41−99.37) in samples with low avidity to 11.76% (95%CI: 4.44−23.87) in those with high avidity (p = 0.01). Of the study participants who were positive for both T. gondii IgM and IgA antibodies, 66.67% had low or equivocal IgG avidity test results compared to 6.25% who tested positive for IgM, were negative for IgA and in whom low or equivocal IgG avidity test results were noted (p = 0.001). This study indicates that in Western Romania, T. gondii IgG seroprevalence is high in females of reproductive age and T. gondii IgA antibodies may be rarely detected during a serologic screening. However, in individuals with demonstrable T. gondii IgG and IgM antibodies, testing for T. gondii IgA may improve the rate for the detection of a recently acquired toxoplasmosis.

Heterogeneity of Platelet Derived Growth Factor Pathway Gene Expression Profile Defines Three Distinct Subgroups of Renal Cell Carcinomas.

BACKGROUND/AIM: We previously described four different vascular patterns (reticular, diffuse, fasciculate, and trabecular) in renal cell carcinoma (RCC) suggesting an early and heterogeneous acquisition of perivascular cells most probably due to a particular PDGF pathway gene expression profile. The aim of the study was to study PDGF pathway gene expression profiles, separately for each vascular pattern. MATERIALS AND METHODS: TaqMan assay for the PDGF pathway was performed on twelve cases of ccRCC previously evaluated by histopathology, immunohistochemistry, and RNAscope. Gene expression profile was correlated with grade, invasion, vascular patterns, and VEGF. RESULTS: PIK3C3 and SLC9A3 genes were overexpressed in all vascular patterns, but they were significantly correlated with high VEGF mRNA in the reticular and diffuse pattern. STAT1, JAK2, SHC2, SRF and CHUK (IKK) were exclusively overexpressed in cases with diffuse vascular pattern. SLC9A3, CHUK and STAT3 were overexpressed in G2 tumors. CONCLUSION: Three ccRCC subgroups were defined: 1) PIK3C3 (VSP34)/SLC9A3 which may be proper for anti PIK3C3 inhibitors; 2) VEGFhigh subgroup where association of anti VEGF may be a benefit and 3) JAK2/STAT1 subgroup, potentially being eligible for anti JAK/STAT therapy associated with IKK inhibitors.

Anti-chloride Intracellular Channel Protein 1 (CLIC1) Antibodies Induce Tumour Necrosis and Angiogenesis Inhibition on In Vivo Experimental Models of Human Renal Cancer.

BACKGROUND/AIM: Chloride intracellular channel protein 1 (CLIC1) is known as a promoter of cancer progression, metastasis, and angiogenesis. Thus, CLIC1 could be a future therapeutic target. This study aimed to evaluate the effect of anti-CLIC1 antibodies on tumour cells and vessels of human renal cell carcinoma (RCC) in rabbit cornea and chick embryo chorioallantoic membrane (CAM) models. MATERIALS AND METHODS: Human cc-RCC xenografts on rabbit cornea and CAM surface were performed. Anti-CLIC1 antibodies were applied for 5 consecutive days on both tumor models. We comparatively evaluated treated and untreated tumors by combining ultrasonography with microscopic techniques. RESULTS: RCC implants rapidly recruited blood vessels and had an exponential growth rate on both tumor models. Anti-CLIC1 antibodies suppressed tumor growth by inducing tumor cell necrosis. Tumor vessels regressed rapidly but not completely during anti-CLIC1 antibodies based therapy. CONCLUSION: Anti-CLIC1 antibodies induced tumor necrosis and tumor vasculature regression in human cc-RCC xenografts in both in vivo experimental models.

Esophageal ulcer associated with mild hemophilia A: case report.

In this paper, we present the case of a 68-year-old male with personal medical history of coagulopathy issues, who presented to our Emergency Room (Emergency County Hospital, Arad, Romania) with bleeding of the superior tract of the digestive system; the case was difficult to manage, thus warranting the intervention of the Department of Gastroenterology. Endoscopy was performed to localize the site of bleeding and to stop the hemorrhage. This procedure was not successful. The patient was transferred to our Intensive Care Unit where different medications, such as proton pump inhibitor, hemostatic agent and prokinetic drugs were administered. Unfortunately, our attempt to stop bleeding failed; this led us to expand our investigation. We focused on a possible hemophilia as the cause of bleeding, which was confirmed as hemophilia A through the coagulometry test after a period of three days. Patient medical history and coagulation test led us to believe that this is a very rare case of a mild hemophilia A. Finally, the correction of Factor VIII deficiency and repeated endoscopic hemostasis clip was able to stop patients bleeding and ensured a favorable clinical evolution of the patient.

Sarcomatoid renal cell carcinoma with clear cells and eosinophilia: a case report and short review of the literature.

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive form of de-differentiated renal cell carcinoma. We report a case of a 79-year-old male who presented himself to the Department of Emergency complaining of macroscopic hematuria for the last two days and a back pain located in the lumbar region persisting for around a month; there were no major changes in the initial laboratory tests. Abdominal ultrasonography identified a renal mass located in the lower pole of the left kidney. The computed tomography (CT) scan with iodine-based contrast revealed the left kidney had a complete deletion of corticomedullary differentiation and a large renal mass located in the lower pole with inhomogeneous iodophilia, which measured around about 15 cm in transversal diameter and 13.6 cm in craniocaudal diameter. Nephrectomy of the left kidney was performed. Histopathological and immunochemistry tests diagnosed a SRCC with clear cells and eosinophilia. We present these findings along with a short review of the literature.

Intracellular Chloride Ion Channel Protein-1 Expression in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Chloride intracellular channel 1 (CLIC1) represents a promising target for personalized therapy. Our aim was to assess CLIC1 expression in clear cell renal cell carcinoma (cc RCC) and identify its possible prognostic role. MATERIALS AND METHODS: Fifty cases of cc RCC were evaluated and selected for immunohistochemistry. CLIC1 expression was correlated with tumor grade, invasion and heterogeneity. RESULTS: A total of 87.5% of the cases were CLIC1 positive, with either a homogeneous (31.42%) or a heterogeneous (68.57%) pattern. Low, mild and strong CLIC1 expressing tumors were defined based on nuclear (N), cytoplasmic (C), membrane (M) or combinations of them (NC, NM, CM, NCM) in terms of CLIC1 distribution. A significant correlation was found between tumor grade and percent of positive tumor cells (p=0.017). For G3 tumors, CLIC1 cytoplasmic expression was strongly correlated with high expression status (p=0.025) and tumor heterogeneity (p=0.004). CLIC1 expression was also correlated with metastasis (p=0.046). CONCLUSION: We defined four cc RCC groups depending on G, CLIC1 expression and pattern: i) G3/NM/low CLIC1+, ii) G2/CM/mild CLIC1+ iii) G1 or G2/NM or CM /high CLIC1+, and iv) G2/M /high CLIC1.