Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM­A protein.

BACKGROUND: The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. METHODS: The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. RESULTS: By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. CONCLUSIONS: The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?

F11 receptor (F11R)/Junctional Adhesion Molecule -A (JAM-A) is a transmembrane protein which belongs to the immunoglobulin superfamily of cell adhesion molecules. F11R/JAM-A is present in epithelial cells, endothelial cells, leukocytes, and blood platelets. In epithelial and endothelial cells, it takes part in the formation of tight junctions. In these structures, molecules of F11R/JAM-A located on adjacent cells form homodimers and thus take part in stabilization of cellular layer integrity. In leukocytes, F11R/JAM-A was shown to play role in their transmigration through the vascular wall. Paradoxically, the function of F11R/JAM-A in blood platelets, where it was primarily discovered, is much less understood. It has been proven to regulate downstream signaling of αIIbß3 integrin and to mediate platelet adhesion under static conditions. It was also shown to contribute to transient interactions of platelets with inflamed vascular wall. The review is aimed at summarizing the current state of knowledge of the platelet pool of F11R/JAM-A. The article also presents perspectives of the future research to better understand the role of this protein in hemostasis, thrombosis, and other processes where blood platelets are involved.

The molecule of a complex name F11R/JAM-A is a protein which was primarily discovered on blood platelets. Later, the presence of the same molecule was confirmed on endothelial cells and epithelial cells. From the moment of the discovery, most of the research was focused on the role of this protein in the latter types of cells. It was found to be an important element of so-called tight junctions. These structures are crucial for maintaining of integrity and selective permeability of cellular layers composed of these types of cells. In the following years, the presence of F11R/JAM-A has also been reported on leukocytes. An important role of specific type of leukocytes is their penetration to the sites of inflammation. Interplay of F11R/JAM-A present on endothelium and that on leukocyte is involved in this process. But what about the role of this protein in blood platelets where it was originally discovered? There is limited knowledge regarding this issue. It was found to play a role in the ability of platelets to adhere to a surface under static conditions, but it is not known if the same is true under flow. Is the protein necessary for platelets to aggregate and form thrombus? Genetically engineered mice were created which lack this protein in blood platelets to answer this question. These platelets were abnormally reactive, as it transpired that the protein plays a role of a negative regulator to one of the most important mechanisms, which triggers platelet aggregation. But is this inhibitory function the only task F11R/JAM-A has to fulfil in platelets? Presented review collects all the knowledge regarding this protein in blood platelets and tries to show interesting routes which need exploration.

The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression.

The F11 Receptor (F11R), also called Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is a transmembrane glycoprotein of the immunoglobulin superfamily, which is mainly located in epithelial and endothelial cell tight junctions and also expressed on circulating platelets and leukocytes. It participates in the regulation of various biological processes, as diverse as paracellular permeability, tight junction formation and maintenance, leukocyte transendothelial migration, epithelial-to-mesenchymal transition, angiogenesis, reovirus binding, and platelet activation. Dysregulation of F11R/JAM-A may result in pathological consequences and disorders in normal cell function. A growing body of evidence points to its role in carcinogenesis and invasiveness, but its tissue-specific pro- or anti-tumorigenic role remains a debated issue. The following review focuses on the F11R/JAM-A tissue-dependent manner in tumorigenesis and metastasis and also discusses the correlation between poor patient clinical outcomes and its aberrant expression. In the future, it will be required to clarify the signaling pathways that are activated or suppressed via the F11R/JAM-A protein in various cancer types to understand its multiple roles in cancer progression and further use it as a novel direct target for cancer treatment.

Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment.

PURPOSE: To examine the involvement of the F11R/JAM-A protein in breast cancer metastasis, we utilized the F11R/JAM-A antagonistic peptide 4D (P4D) in experiments of transendothelial migration (TEM) of breast cancer cells. METHODS: Experiments were conducted in the mouse 4T1 breast cancer model utilizing the human mammary epithelial cell and endothelial cell lines. The levels of soluble F11R/JAM-A (sJAM-A) in the murine plasmas were measured by ELISA. Levels of F11R/JAM-A mRNA and protein in cell lines were assessed by qRT-PCR and Western blot, respectively. Cell surface expression of F11R/JAM-A was demonstrated by flow cytometry. Functional tests included the TEM of breast cancer cells and adhesion of breast cancer cells to the endothelium. The endothelial permeability was studied by fluorescent tracer assay and by the Real-Time Cell Analysis (RTCA). RESULTS: The tumor inducers Tß4 and TGF-ß1 reduced the levels of sJAM-A in murine plasma, and reduced the F11R/JAM-A protein levels in the human microvascular endothelial cell line HMEC-1. The adhesion and TEM measured between breast cancer cells and inflamed or Tß4-treated endothelium were inhibited by P4D. The presence of P4D did not destabilize the pre-existing tight junctions in the endothelial monolayer. The barrier-protecting effect of P4D was stronger than that of forskolin, when a booster dose of P4D was applied to the inflamed endothelium. CONCLUSIONS: F11R/JAM-A protein can be considered as a novel target in the treatment of breast cancer metastasis. In vivo and clinical studies are needed to further investigate the effectiveness of F11R/JAM-A-derived peptide as a possible anti-metastatic drug.

No association between MRI changes in the lumbar spine and intensity of pain, quality of life, depressive and anxiety symptoms in patients with low back pain.

INTRODUCTION: The association between changes in magnetic resonance imaging (MRI) and clinical symptoms in patients with low back pain (LBP) is unclear. AIM: To evaluate correlations between combined MRI findings of the lumbar spine (LS) and pain intensity, depressive and anxiety symptoms and quality of life in patients with LBP. MATERIAL AND METHODS: 200 subjects (93 men and 107 women; mean age 51.42 ± 13.21 years) with LBP referred for MRI were enrolled in the study. All patients completed the Hospital Anxiety and Depression Scale (HADS), Quality of Life Scales (EQ-5D, EQ-VAS) and the Visual Analogue Scale (VAS). MRI scans were assessed according to a scoring system prepared by the authors, and the total MRI score was calculated. RESULTS: The mean total MRI score was 11.59 ± 6.73 points (range 0-50 points) and was higher in men than in women (p = 0.015). A correlation was observed between total MRI score and age (p < 0.001) and between total MRI score and BMI (p = 0.005). An association was found between total MRI score and EQ-5D (p = 0.012) and HADS-D results (p = 0.003). VAS and HADS-A results did not correlate with MRI score. When multivariate analysis was done, the total MRI score was only significantly related to age and BMI, and association between the total MRI score and EQ-5D or HADS-D results was not confirmed. Decreased quality of life was associated with increased intensity of pain and depressive and anxiety symptoms. CONCLUSIONS: Combined MRI changes in LS do not correlate with pain intensity, depressive and anxiety syndromes or quality of life in patients with LBP.

Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI).

Due to the fact that overweight or obesity is accompanied by hormonally active adrenal tumors: Cushing Syndrome-(CS) and Subclinical Cushing Syndrome (SCS), it is of high interest the correlation between different adipokines and cytokines secreted by adipose tissue, with metabolic disorders and hormonal activity in this group. Even in non-functioning adrenal incidentalomas (NFAI) elevated risk for cardiovascular disease and metabolic syndrome was demonstrated. The aim of the study was to investigate plasma adiponectin, leptin, resistin, tumor necrosis factor α (TNFα), interleukin 6 (IL6) and monocyte chemoattractant protein 1 (MCP1) levels in patients with NFAIs and healthy subjects. The study included 18 NFAI patients and 18 healthy subjects. The groups were homogeneous in terms of age, sex and body mass index (BMI). Patients with NFAI showed significantly higher circulating levels of pro-inflammatory cytokines compared to healthy controls (MCP 1: p < 0.001; TNFα p = 0.021; IL6 p = 0.012). On the other hand, adiponectin concentration was significantly lower in the NFAI group (p = 0.034). The serum leptin and resistin concentrations did not differ significantly between the two groups. Acquired results were not dependent on glucocorticoid and catecholamine secretion in NFAI patients. Also, there were no clear correlations between BMI and cytokine levels. It is possible that increased risk for cardiovascular and metabolic diseases reported in NFAI patients is at least partially dependent on adipose tissue activity.

[Sexual quality of life in patients with low back pain and the radiological changes evaluated in magnetic resonance].

OBJECTIVE: Introduction: Literature data concerning the association between the back pain syndrome and the quality of sexual life are rare, especially in the Polish literature. There are also no reports on the association between magnetic resonance (MRI) results and sexual satisfaction in patients with low back pain (L-S). The aim: To assess the association between the severity of degenerative-discopathic changes in the MRI of L-S spine and the quality of sexual life in patients with low back pain. PATIENTS AND METHODS: Materials and methods: The study involved 200 patients (107 women and 93 men), referred for MRI of the L-S spine due to the back pain syndrome. The assessment of satisfaction with sexual life at present and before the disease was made by the self-constructed questionnaire and with the use of the Question No. 8 of the Oswestry Questionnaire (ODI). In addition, the VAS (Visual Analogue Scale) was used. MRIs were analyzed based on the author's scoring scale, assessing selected radiological changes at levels L1-S1. The total score was in the range of 0-50 points. RESULTS: Results: There was a statistically significant decrease in the quality of sexual life (8.9 points vs 6.3 points) (<0.001). Back pain did not affect sexual life only in 36.9% of respondents. 26.5% patients were sexually inactive, 7.5% of them declared that pain was the reason for this. There was no statistically significant correlation between the intensity of radiological changes and satisfaction with sexual life. CONCLUSION: Conclusions: Back pain affects the patients' sexual life. There was no association between the severity of degenerative-discopathic changes assessed in the MRI and the quality of sexual life in patients with L-S back pain syndrome.

[Patient with spine pain and magnetic resonance imaging result].

Degenerative spine disease is a serious social problem. In most cases, it causes pain and neurological symptoms. Most patients are therefore referred for magnetic resonance imaging (MRI). The article discusses the relationship between back pain and magnetic resonance changes. The signification of some of the radiological symptoms remains controversial. Some of them are markers of acute pain, others may be clinically insignificant, occurring with age. Authors presents some of the magnetic resonance alterations and based on the latest articles discusses their clinical significance. The issues of performing routine, control MRI examination due to chronic back pain and the incidence of new radiological findings were also discussed.

Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors.

BACKGROUND: The authors have examined the immunohistochemical expression of several proteins and their relationship with adrenal cortical carcinoma (ACC) diagnosis and progression. MATERIALS AND METHODS: A total of 83 patients with benign and malignant adrenal cortex tumors operated on in a single center were included in the study. Expression of the following proteins was examined: steroidogenic factor 1 (SF1), insulin growth factor 2 (IGF2), Ki67, p53, as well as adiponectin (Adipo R1, Adipo R2), and leptin (Ob-R) receptors. RESULTS: Multivariate analysis revealed that the expression of SF1, IGF2, and Adipo R1 and R2 receptors was associated with ACC diagnosis. An acknowledged proliferation marker Ki67 was related with the size of ACC and was an independent ACC diagnosis marker. The authors also assessed the relationship between immunohistochemical parameters and overall survival (OS) and disease progression. Only high IGF2 expression was associated with longer OS (P = 0.025). The most significant one for the prognosis of ACC patients was tumor resectability of the primary tumor. More favorable prognosis was found for young men (P = 0.033). CONCLUSIONS: The presented data indicate that immunohistochemical assessment (of IGF2, SF1, Adipo R1, and R2 receptors' expression) may be useful in making the diagnosis of uncertain ACC cases.

The Bony Bankart Lesion: How to Measure the Glenoid Bone Loss.

An osseous Bankart lesion is commonly seen in patients with an anterior shoulder dislocation. It is defined as a detachment of the anteroinferior labrum associated with a glenoid rim fracture. Radiological studies are crucial not only for detecting glenoid bone defects but also for measuring the amount of bone loss. The precise quantification of the bony defect is crucial for the therapeutic desicion-making and clinical outcomes. Although we know that major glenoid bone loss requires surgical intervention, none of the studies performed so far answered the question what size of the defect should be an indication for open surgery procedures. Moreover, there is still no consensus on the exact percentage of glenoid loss that results in a higher risk of re-dislocations. In our opinion, there is a strong need for a consensus on universally accepted measuring techniques of the glenoid defect as well as on algorithms with validated glenoid bone loss threshold values for therapeutic decision-making. In this study, we review the techniques described so far in the literature and try to assess if any of these techniques should be treated as a leading method of detecting and quantifying osseous glenoid lesions.

Right Aortic Arch with Aplasia of the Left Brachiocephalic Trunk Presented as Systolic Blood Pressure Difference Between Upper Extremities.

BACKGROUND: The right aortic arch with mirror-image of branching arteries without coexisting congenital heart disease is a very rare anomaly. CASE REPORT: We report a case of the right-sided aortic arch with aplasia of the left brachiocephalic trunk in a 64-year-old women, presenting difference in systolic blood pressure between upper extremities. The history of the patient and angio-CT findings were described and visualized with images. CONCLUSIONS: The knowledge of vascular variations is important for the clinical and therapeutic aspects.

Primary malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland.

An increased number of adrenal tumors are now diagnosed due to the increased number of abdominal CT scans being performed. We present the first case of malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland. An abdominal CT scan demonstrates unilateral adrenal lesion which suggests pheochromocytoma or adrenal carcinoma. Laboratory examinations revealed a slight increase of 24-h urine vanillylmandelic acid and 24-h urinary methanephrine excretion. Histological examination revealed two intermingled tumor cell proliferations-diffuse B cell lymphoma and pheochromocytoma.Unexpected coexistence of catecholamine-producing tumor with the other adrenal lesion can lead to serious complications of diagnosis and treatment. The adequate preparation for surgery can protect patient from threatening catecholamine crisis.

Sunitinib treatment for multifocal renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (NET) in patient with Von Hippel-Lindau disease. Case Report.

OBJECTIVE: Von Hippel-Lindau disease (VHL) is an autosomal, dominant, hereditary disease occurring in approximately one in 36,000 births. VHL disease produces a variety of tumors and cysts in the central nervous system and visceral organs. Surgical management, when possible, improves prognosis and extends patient's life. When surgery is impossible, treatment with tyrosine kinase inhibitors demonstrates encouraging response rates. MATERIAL AND METHOD: We present a 60-year old patient with coexistence of multifocal renal cell carcinomas (RCC) and pancreatic neuroendocrine tumor (NET) in VHL disease, who received Sunitinib as the best option of treatment. RESULTS: Progression - free survival time is over 4 years. Regarding her acceptable tolerance for tyrosine kinase inhibitors, medical treatment is continued. CONCLUSION: RCC and pancreatic NET associated with VHL are responsive to Sunitinib for prolonged periods of time. Tyrosine kinase inhibitors treatment for patients with multiple neoplasms associated with VHL disease may too be considered. Sunitinib showed acceptable toxicity.

The collection of five interesting cases of adrenal tumors from one medical center.

INTRODUCTION: Adrenal tumors are detected incidentally in 4 to 8% of patients in imaging studies. Adenomas, pheochromocytomas and adrenocortical carcinomas represent the most common tumors of the adrenal glands. Rarely are final histopathological reports are surprising. AIM: The aim of our study is a retrospective analysis of selected clinical characteristics and hormonal studies in five cases of rare adrenal tumors. MATERIALS AND METHODS: We present five interesting cases of adrenal tumors: two medullary hyperplasia, one adenomatoid tumor, one hydatid cyst and a primary angiosarcoma of the adrenal gland. The final diagnosis was established by means of microscopic examination of the specimens. CONCLUSIONS: The number of adrenal tumors was increased due to widespread use of imaging procedures. In patients without any known extra-adrenal malignancy most lesions are benign, non-hyper functioning adenomas. Adrenal tumors should be evaluated biochemically and radiologically.

Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).

(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer (p = 0.000814), the number of mucus peaks was statistically higher (p = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

The role of selected adipokines in tumorigenesis and metabolic disorders in patients with adrenal tumors.

Recently, more and more attention has been directed to the role of adipose tissue and adipocytokines in the pathogenesis of metabolic and inflammatory disorders in humans. Excess fat tissue has also been associated with a higher risk of malignancies. Advances in the research on the role of adipokines in adrenal tumors may elucidate the relationship between various types of adipose tissue (visceral, subcutaneous, and periadrenal) and metabolic disorders observed in hormonally active adrenal tumors, as well as associations with adrenal cortex cancer. In patients with active or cured Cushing syndrome, increased leptin and resistin concentrations as well as release of pro-inflammatory cytokines can be associated with cardiovascular risk. Also, the renin-angiotensin-aldosterone system in patients with primary hyperaldosteronism may affect the metabolic activity of the adipose tissue. Elevated resistin concentrations in this group of patients are associated with morphological changes of the myocardium independently of the effects of the metabolic syndrome. Further, it has been suggested that hypoadiponectinemia comprises an additional factor in the pathogenesis of carbohydrate metabolism disorders and the risk of cardiovascular complications in pheochromocytoma patients. Understanding the mechanisms of action of adipokines may be important in developing prophylactic and therapeutic strategies in hormonally active and malignant tumors of the adrenal glands.

Review of Diagnostic Modalities for Adrenal Incidentaloma.

Adrenal incidentalomas are common findings in clinical practice, with a prevalence of up to 4.2% in radiological studies. Due to the large number of focal lesions in the adrenal glands, it can be challenging to make a definitive diagnosis and determine the appropriate management. The purpose of this review is to present current diagnostic modalities used to preoperatively distinguish between adrenocortical adenoma (ACA) and adrenocortical cancer (ACC). Proper management and diagnosis are crucial in avoiding unnecessary adrenalectomies, which occur in over 40% of cases. A literature analysis was conducted to compare ACA and ACC using imaging studies, hormonal evaluation, pathological workup, and liquid biopsy. Before deciding on surgical treatment, the nature of the tumor can be accurately determined using noncontrast CT imaging combined with tumor size and metabolomics. This approach helps to narrow down the group of patients with adrenal tumors who require surgical treatment due to the suspected malignant nature of the lesion.

Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome.

Infertility has been recognized as a civilizational disease. One of the most common causes of infertility is polycystic ovary syndrome (PCOS). Closely interrelated immunometabolic mechanisms underlie the development of this complex syndrome and lead to infertility. The direct cause of infertility in PCOS is ovulation and implantation disorders caused by low-grade inflammation of ovarian tissue and endometrium which, in turn, result from immune and metabolic system disorders. The systemic immune response, in particular the inflammatory response, in conjunction with metabolic disorders, insulin resistance (IR), hyperadrenalism, insufficient secretion of progesterone, and oxidative stress lead not only to cardiovascular diseases, cancer, autoimmunity, and lipid metabolism disorders but also to infertility. Depending on the genetic and environmental conditions as well as certain cultural factors, some diseases may occur immediately, while others may become apparent years after an infertility diagnosis. Each of them alone can be a significant factor contributing to the development of PCOS and infertility. Further research will allow clinical management protocols to be established for PCOS patients experiencing infertility so that a targeted therapy approach can be applied to the factor underlying and driving the "vicious circle" alongside symptomatic treatment and ovulation stimulation. Hence, therapy of fertility for PCOS should be conducted by interdisciplinary teams of specialists as an in-depth understanding of the molecular relationships and clinical implications between the immunological and metabolic factors that trigger reproductive system disorders is necessary to restore the physiology and homeostasis of the body and, thus, fertility, among PCOS patients.