Diagnostic Value of SALL4 and OCT3/4 in Pediatric Testicular Tumors.

Testicular tumors (TTs) are rare in children, posing diagnostic and therapeutic challenges. This retrospective study evaluates the diagnostic and prognostic utility of SALL4 and OCT3/4 in pediatric TTs. We analyzed 18 cases of different types of TTs using immunohistochemistry (IHC) to assess SALL4 (Spalt-like transcription factor 4) and OCT3/4 (Octamer binding transcription factor 3/4) expression. SALL4 was positive in 83.3% of tumors, while OCT3/4 was positive in 38.9% of tumors, with a significantly higher prevalence in patients aged 12-18 years compared to those aged 0-11 years (p = 0.013). Mixed germinal cell tumors were significantly more frequently associated with OCT3/4 (p = 0.003), and a high immunostaining expression for SALL4 was observed primarily in yolk sac tumors and embryonal carcinoma. Our findings suggest that SALL4 and OCT3/4 immunostaining can aid in accurate diagnosis and treatment planning, and underscores the importance of OCT3/4 as a predictive factor in pediatric testicular tumors, highlighting its substantial correlation with tumor type and its impact on treatment response. These markers may guide personalized therapeutic strategies, potentially improving patient outcomes.

Aging of Superficial Musculoaponeurotic System of the Face-Novel Biomarkers and Micro-CT Relevance of Facial Anti-Gravity Support.

The soft superficial tissues of the face are against gravity through an intricate network of ligaments and ligamentous attachments. The aim of this investigation is to delineate the relationship between the muscular, fibrous, and vascular components of the superficial musculoaponeurotic system of the face (SMAS) at the level of its periosteal fixation areas from advanced radiological and novel biomarkers' perspectives. These areas represent key points underlying skin aging and the longevity of restorative surgery results. Methods: This study was carried out on 37 surgical specimens, excised from patients admitted for surgery. On the excised specimens, we used special immunohistochemical techniques, such as markers for collagen type III, angiogenesis, vascular endothelium (I-CAM2) and muscle fibers (MYH2). We performed a micro-CT evaluation of these 37 specimens. Results: The results of this study showed different radiologic and IHC characteristics of the means of periosteal fixation of the SMAS. Evidence of morphohistological and radiological peculiarities of the retaining ligaments highlights new data for future functional studies of these structures. Our research must be continued with larger groups of subjects and through detailed methodological studies of vascular microperfusion and could represent an important new step in biotissue engineering and the customization of surgical techniques involving the sub-SMAS layers.

Assessment of Molecular Markers in Pediatric Ovarian Tumors: Romanian Single-Center Experience.

Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.

BRAF V600E Mutation in Malignant Melanoma-A Romanian Research Experience.

Background and Objectives: The most common mutation in malignant melanoma (MM) is the single-point mutation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) oncogene. Our study aims to evaluate BRAF V600E mutation, highlighting its frequency differences in primary versus metastatic MM. Materials and Methods: The study group comprised 133 patients diagnosed with MM in several county hospitals of the north-eastern region of Romania who have been assigned for investigation into BRAF V600E mutation in the private medical system. The material consisted of archived formalin-fixed paraffin-embedded (FFPE) blocks. BRAF V600E mutation was identified using the fully automated IdyllaTM BRAF mutation test system. Results: Out of the total of 133 cases, 78 cases were primary tumors, while 55 cases were metastatic MMs. Genetic analysis revealed the presence of BRAF V600E mutation in 66 cases (49.62%) and the wild-type genotype in 67 cases (50.37%). We found a statistically significant difference of the mutation frequency according to age (p = 0.0072). The mutated genotype was found in 45 cases out of 78 primary MMs (57.69%) and in 21 cases out of 55 secondary MMs (38.18%), with a statistically significant difference in favor of primary tumors (p = 0.0413). The correlations between the histopathological types, Clark's level, Breslow index, ulceration, and lymphovascular invasion, respectively, and the mutated genotype were not statistically significant. BRAF V600E mutation was identified in 15 out of 40 secondary tumors with lymph node location (37.5%) and in 6 out of 15 secondary tumors with another location (40%) without statistically significant differences between the mutation frequency and the location of the secondary tumors. Conclusions: Our results support MM high genetic heterogeneity, pointing out the relationship between BRAF V600E mutation and several clinicopathological characteristics, in primary and metastatic MMs, stressing the importance of BRAF testing implementation in Romania.

Significance of the Galectin-8 Immunohistochemical Profile in Ovarian Cancer.

Ovarian cancer (OC) still registers a high prevalence in female gynecological pathology. Given the aggressiveness of the tumor and the lack of response to conventional therapies, a current research interest is the identification of new prognostic markers. Gal-8, a member of the galectin family of molecules, involved in tumorigenesis, disease progression, and metastasis, has been assigned as a valuable tumor prognostic factor, and its inhibition may open new perspectives in cancer therapeutic management. Few studies have been carried out so far to evaluate OCs' galectin profiles. Our study aimed to characterize the Gal-8 profile in different types of ovarian neoplasia and to demonstrate its prognostic value. Our study group comprised 46 cases of OCs that were histologically and immunohistochemically investigated, introduced to Gal-8 immunoreactivity, qualitatively and semi-quantitatively evaluated, and correlated with clinicopathological characteristics. Gal-8 immunoexpression was identified in tumor epithelial cells, showing a dominant nuclear labeling, followed by cytoplasmic and mixed, nuclear, and cytoplasmic labeling. Significant differences between tumor histotypes were found in the statistical analysis between low and high Gal-8 immunoscore levels and clinicopathological features: HGSC (eng.= high-grade serous carcinoma) vs. LGSC (eng. = low-grade serous carcinoma), pathogenic types (type I vs. type II), and tumor grades. Our results reflect Gal-8 expression variability depending on the histological type and subtype, the progression stages, and the degree of differentiation of ovarian tumors, supporting its value as a prognostic factor. Our findings open perspectives for larger studies to validate our results, along with a potential Gal-8 transformation into a future therapeutic target.

Morphofunctional and histological patterns of blood vessels in the superficial cervicofacial musculoaponeurotic system in midlateral face regions.

OBJECTIVE: The superficial cervicofacial musculoaponeurotic system (SMAS) is a complex network formed by mimic muscles and conjunctive tissue of the superficial fascia of the face.This study aimed to introduce new anatomofunctional data on the importance of the trans-SMAS distribution pattern of the skin microperfusion of the face and to underline the role of SMAS in maintaining the homeostasis of the vascular network that crosses it. Considering the fibrous and muscular matrix of the SMAS, using COLIII and MyoH2 antibodies, together with endothelial immunohistochemistry(IHC)intercellular adhesion molecule 2 marker, we determined the correlation of these structures and their interaction. METHODS: This study included 33donors of SMAS tissues, which have been stained withregular hematoxylin and eosin (HE), and three different IHC markers have been used (collagen III, muscular tissue, and blood vessels). The samples were collected from parotid, masseteric, jugal, and zygomatic regions. Magnetic resonance angiography was used to identify the main vascular sources of the midlateral regions of the face of another 47 patients. RESULTS: Significant differences in topographic arrangement, density, and relations of the microsopic vasculature were observed between each of the four regions. Major differences were identified between the role of SMAS in each of these regions, from the parotid capsule to masseteric fascia, transition mobile part, and attaching manners in the zygomatic subunit. CONCLUSIONS: Blood vessel topography must be related with the surrounding conjunctive and muscular tissue, especially regarding facial SMAS. Intrinsic relations between these three components of the SMAS and nervous fibers can provide us important hints on the functionality of the whole system.

Vitamin D-The Iceberg in Endometriosis-Review and Meta-Analysis.

(1) Background: Although vitamin D has many known biological effects, very little research has been conducted on how vitamin D may be related or play a role in endometriosis. The aim of our study was to perform an evaluation regarding vitamin D levels and possible implications in endometriosis through a statistical analysis of the data collected from the included studies. (2) Methods: For this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and PubMed/Internet portal of the National Library of Medicine databases using several keywords related to our topic. (3) Results: Only nine articles were identified as complete or possessing the capacity to compute all available data. We totalized a number of 976 patients with endometriosis and 674 controls. From the nine studies included in our analysis, three of them claim there is no difference between women with and without endometriosis concerning 25(OH) vitamin D levels; however, the other six studies found significant differences regarding this aspect. (4) Conclusions: Our results underscored the complexity of analyzing the role of the vitamin D complex in a challenging condition like endometriosis and suggest that focusing on the tissue level might be essential to obtain accurate answers to our inquiries.

Galectin-8 Immunohistochemical Profile in Pancreatic Ductal Adenocarcinoma: Emerging Evidence for Its Prognostic Role.

Pancreatic ductal adenocarcinoma (PDAC) represents the most frequent pancreatic malignancy, with stromal and epithelial heterogeneity reflected in outcome variability. Therefore, a molecular classification is promoted based on the validation of new diagnostic and prognostic markers. Galectin-8 (Gal8) has been pointed out as a prognostic factor for survival in several types of tumors. Due to limited existing data on PDAC, our study aimed to evaluate the Gal8 profile in PDAC alongside its prognostic status. A total of 87 cases of PDAC were immunohistochemically investigated, and Gal8 immunoexpression was qualitatively and semi-quantitatively assessed and correlated with classical clinicopathological parameters and survival. Gal8 immunoexpression was identified to be mostly nuclear and cytoplasmic, followed by exclusively cytoplasmic and exclusively nuclear. A statistical analysis between Gal8 profiles defined by negative, low, or high scores and clinicopathological characteristics showed significant differences in tumor size, pN stage, and lympho-vascular invasion. Although a Cox regression analysis did not support the prognostic status of Gal8, and we did not confirm its relationship with OS, our results show that exclusively nuclear labeling was associated with an increased mean OS compared with cytoplasmic and nuclear labeling (29.37 vs. 17.93 months). To the best of our knowledge, this is the first study to report a detailed pattern of Gal8 immunostaining in PDAC and to correlate this pattern with clinicopathological characteristics and survival. Our results show that Gal8 immunoexpression is associated with a more aggressive phenotype, thus opening perspectives for larger studies to validate Gal8 as a prognostic factor.

Vitamin D and Mitosis Evaluation in Endometriosis: A Step toward Discovering the Connection?

(1) Background: The effects of serum vitamin D levels, the vitamin D receptor (VDR), and phosphohistone H3 (PHH3) in endometriosis were investigated in two cohorts of women with this pathology: those receiving hormonal treatment and those without treatment. (2) Methods: In 60 cases of women with endometriosis (26 with progestin treatment and 34 without), paraffin-embedded endometriosis tissue samples retrieved after surgery were immunohistochemically (IHC) analyzed to determine the expression statuses of VDR and PHH3. In addition, serum levels of 25(OH) vitamin D were assessed for each patient. (3) Results: The serum 25(OH) vitamin D evaluations revealed higher levels of 25(OH) vitamin D in women with treatment compared with those without. The positive IHC indexes of VDR and PHH3 in these two groups were compared. Vitamin D receptor levels were positively correlated with PHH3 levels, both being increased in patients without treatment. (4) Conclusions: Serum 25(OH) vitamin D levels and IHC analysis of VDR and PHH3 can be used as additional tools for risk stratification and prognostic assessment in patients with endometriosis.

Effects of Progestin on Modulation of the Expression of Biomarkers in Endometriosis.

BACKGROUND: Our study aimed to examine the osteopontin (OPN) serum levels and tissue expression of CD44 and OPN in endometriosis-affected women both undergoing and not undergoing progestin treatment, and also to determine their involvement in the pathogenesis of endometriosis. METHODS: Using an ELISA kit, we evaluated the OPN serum levels of healthy and endometriosis-affected women both undergoing and not undergoing progestin treatment. Immunohistochemical (IHC) analyses were used to assess the endometriotic tissue expressions of CD44 and OPN. RESULTS: There were statistically significant higher OPN serum levels in the healthy control group compared to the women with endometriosis. Furthermore, there were higher OPN serum levels in the endometriosis-affected women undergoing the progestin treatment, but the difference did not reach statistical significance. In comparison to OPN, CD44 expression was significantly higher in all the endometriotic tissue glands and stroma, regardless of the patient's treatment status. Compared to the group receiving therapy, the OPN levels were higher in the endometriosis group not receiving therapy. OPN's robust cytoplasmic expression seemed to be associated with the non-treatment group. CONCLUSION: Endometriosis, CD44, and OPN appear to be closely related. This study suggests that endometriosis that has not been treated has an immunological profile distinct to endometriosis that has received treatment.

Periostin in ovarian carcinoma: from heterogeneity to prognostic value.

INTRODUCTION: Periostin (POSTN), an extracellular matrix protein, is involved in tumor-associated extracellular matrix (ECM) remodeling. However, its potential value as a prognostic and/or predictive factor has not yet been confirmed. The present study aims to assess POSTN expression separately in tumor cells and stroma of different ovarian carcinoma (OC) histological types, and its relationship with clinicopathological features. MATERIAL AND METHODS: 102 cases of different histological OC subtypes were immunohistochemically investigated, for POSTN expression assessment in both epithelial tumor cells and tumor stroma. Statistical analysis was performed to correlate POSTN profile with clinicopathological characteristics, therapeutic response, and survival. RESULTS: POSTN expression in epithelial tumor cells was significantly correlated with POSTN expression in tumor stroma. The expression of POSTN in tumor cells was associated with histological type, tumor type (type I and II), tumor recurrence, progression-free survival (PFS), and overall survival (OS), whereas stromal POSTN expression was significantly correlated with age, histological type, tumor type, grade, and stage, residual disease, tumor recurrence, response to chemotherapy, and OS. Survival analysis revealed significant differences of PFS and OS in patients with high POSTN expression in tumor cells and negative stromal POSTN expression compared to patients with low POSTN expression in tumor cells and positive stromal POSTN expression (PFS: hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.33-3.37, P = 0.002; OS: HR = 1.78, 95% CI: 1.09-2.89, P = 0.019). CONCLUSIONS: The comparative assessment of POSTN immunoexpression in two tumor compartments: in tumor cells and stroma, by use of different scoring systems revealed that higher stromal POSTN levels are evidently correlated with unfavorable clinical features and poorer prognosis, while POSTN expression in tumor cells seems to be associated with a better patient outcome.

The Impact of the COVID-19 Pandemic on Quality Education of the Medical Young Generation.

(1) Generating the need to impose social distancing to reduce the spread of the virus, the COVID-19 pandemic altered the ways in which the teaching process normally happens. The aim of our study was to determine the impact of online teaching on medical students during this period. (2) Our study included 2059 medical, dental and pharmacy students from the University of Medicine and Pharmacy "Grigore T. Popa", Iasi, Romania. We used a modified metacognition questionnaire after translation into Romanian and validation. Our questionnaire included 38 items, and it was divided into four parts. Academic results and preferences regarding the on-site or online courses, information regarding practical training, self-awareness in terms of one's feelings such as anger, boredom and anxiety and also substance use linked to online teaching, and contextualization of the relationship with colleagues, teachers, friends and family were among the most important points evaluated. A comparison was made between preclinical and clinical students. A five-item Linkert-like scale was used for rating the answers in the last three parts that evaluated the impact of the SARS-CoV-2 pandemic on the educational process. (3) Preclinical medical students, compared to preclinical dental students, obtained statistically significant improvements in their evaluation results, with fewer failed exams (p < 0.001) and with similar results being obtained by comparing dental with pharmacy students. All students obtained statistically significant improvements in their academic results during the online evaluation. A statistically significant increase in anxiety and depression with a p-value of <0.001 was registered among our students. (4) The majority found it difficult to cope with this intense period. Both teachers and students found it difficult to adjust on such short notice to the challenges posed by the new concept of online teaching and learning.

COVID-19 Pandemic Affects Children's Education but Opens up a New Learning System in a Romanian Rural Area.

(1) Background: In the context of the COVID-19 pandemic, the educational system in Romania faced major challenges. Online knowledge development was necessary and mandatory during this time; (2) Methods: our study included a group of 140 preadolescents and used a phenomenology qualitative method to investigate if the novel online teaching, implemented in a hurry during the pandemic without any previous teacher training, managed to replace face-to-face teaching; (3) Results: The students have expressed their joy for online courses, as long as they are kept interactive. Even though they feel nervous and worried when it comes to evaluation, the students claim they feel capable to learn all of the learning materials. Most of them are pleased by classes and do not get bored during them, feeling constantly motivated to actively participate in dialogue; (4) Discussions: Despite the lack of teaching-method standardization, our learning providers succeeded in accomplishing their tasks during online courses. Even in remote rural areas, they managed to assure the means for these children to access and take part in online courses; (5) Conclusions: our learning system must offer teachers the possibility to emphasize online education using adequate training programs aiming to develop technical and online pedagogical skills.

Epidemiology of Adverse Outcomes in Teenage Pregnancy-A Northeastern Romanian Tertiary Referral Center.

Background: Despite being a very well-documented subject in the literature, there are still conflicting results regarding teenage pregnancies and their fetal outcomes. Methods: We conducted a retrospective, comparative cohort study that included 1082 mothers aged less than 18 years, compared to 41,998 mothers aged over 18 years, who delivered in our tertiary referral center between January 2015 and December 2021. To check for significant differences between the two groups, the chi-qquared or Fisher's test for categorical variables were used. Results: We detected statistically significant higher rates of fetal malformation, premature birth, FGR and SGA fetal growth conditions, preeclampsia, condylomatosis and vaginal infection with E. coli in our cohort of teenagers. In this subpopulation of teenagers, the rate for premature birth at less than 32 weeks of gestation was 3.26-fold higher and 3.25-fold higher for condylomatosis, and these results referred to the cohort of adult patients (>18 years old) that gave birth in the same interval of time. Conclusions: Teenage pregnancies still remain a major health problem that burdens all countries worldwide regardless of their income. It needs solutions initially to prevent pregnancy in this young age segment and last but not least to improve both maternal and fetal outcomes.

Intravascular leiomyoma­A rare case in the context of Covid­19 outbreak: A case report.

The present study reported a case of a uterine leiomyoma with an unusual growth pattern featuring areas of intravascular leiomyomatosis, rarely described in the international literature available in English. It presented the case of a 44-year-old woman who, fearing the Covid-19 outbreak, postponed the recommended surgical intervention to remove a uterine leiomyoma. The two-year delay worsened the symptoms, doubled the size of the tumor, and facilitated the development of intravascular leiomyomatosis. It was possible to establish the correct diagnosis only after the histopathological examination of the excised uterine myoma, as it was not suspected prior to surgery. No other vascular tumors were identified via magnetic resonance imaging and computed tomography imaging investigations. The careful follow-up of recovering patients is essential because of the high recurrence rate of such tumors and their potential to behave aggressively, possibly even fatally. Clinicians should be aware of this rare condition and its cardiovascular implications to improve the initial and long-term management of such cases.

Primary Clear Cell Adenocarcinoma of the Uterine Cervix in a 14-Year-Old Virgin Girl: Case Report.

Cervical cancer is rare in adolescent and pediatric populations, with adenocarcinoma being the most commonly reported. Clear cell adenocarcinoma of the uterine cervix accounts for only 4% of all adenocarcinoma cases, and about two-thirds are associated with intrauterine diethylstilbestrol (DES) exposure. We report the case of a 14-year-old virgin girl who presented with a 1-month-long history of abnormal vaginal bleeding and lower abdominal pain. Transabdominal pelvic ultrasound examination revealed the presence of an irregular, homogeneous cervical mass that was 7 cm in size. Therefore, a magnetic resonance imaging (MRI) scan was performed to establish the origin of the tumor and its relationship to adjacent pelvic organs. Furthermore, a vaginoscopy was performed to identify the tumor, and a cervical biopsy was performed. Immunohistochemical and anatomopathological studies resulted in the diagnosis of non-HPV(Human Papilloma Virus)-related clear cell adenocarcinoma of the cervix. Following the oncological examination, she was admitted for radiotherapy. The patient had no maternal history of DES exposure in utero. Even though the number of cases in the literature is low, most of the virgin girls diagnosed with clear cell adenocarcinoma of the cervix have a fatal prognosis because of the delay in making a correct diagnosis.

Hormonal, apoptotic, proliferative and inflammatory markers' expression in Desogestrel-treated women with ovarian endometriosis.

Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.

Uterine Fibroids and Pregnancy: A Review of the Challenges from a Romanian Tertiary Level Institution.

BACKGROUND AND OBJECTIVES: Uterine fibroids are relatively common in reproductive-age women and are directly linked to pregnancy. There are many debates about performing a myomectomy at the same time as a caesarian section (CS) in such cases due to the risk of a hemorrhage. Our study aims to investigate fibroid features and their evolution in pregnancy, complications of a myomectomy during CS and maternal and fetal obstetric outcomes of pregnancies with fibroids. MATERIALS AND METHODS: We realize a prospective study that includes 57 patients with fibroids in pregnancy diagnosed in January 2017-June 2019. We analyze the number, the location and the growth of fibroids during pregnancy and the maternal and fetal outcome. We appreciate the bleeding in patients with a myomectomy and without a myomectomy during CS, using hemoglobin values before and after birth. RESULTS: Most of the patients present single fibroids that are 30-160 mm in size, located on the anterior uterine wall. Vaginal delivery is used in 7% of women, whereas 85.96% deliver by CS. In addition, 68% of fibroids are diagnosed in the first trimester. In most cases, the fibroid has maximum growth in the second trimester of pregnancy. The myomectomy rate for fibroids during CS is 24.48. Hemoglobin values showed no statistically significant difference between the two groups with and without myomectomy. The operating time is double for the group with a myomectomy associated with a CS. The results of the obstetric outcomes are abortion in 7% of all patients, whereas premature delivery and births at term are 9.43% and 90.57%, respectively. CONCLUSIONS: The decision of performing a myomectomy during pregnancy can be a challenge and must be performed for selected cases. This procedure may have several benefits, such as avoiding another operation to remove fibroids.

The Interplay between Tumour Microenvironment Components in Malignant Melanoma.

Malignant melanoma has shown an increasing incidence during the last two decades, exhibiting a large spectrum of locations and clinicopathological characteristics. Although current histopathological, biochemical, immunohistochemical, and molecular methods provide a deep insight into its biological behaviour and outcome, melanoma is still an unpredictable disease, with poor outcome. This review of the literature is aimed at updating the knowledge regarding melanoma's clinicopathological and molecular hallmarks, including its heterogeneity and plasticity, involving cancer stem cells population. A special focus is given on the interplay between different cellular components and their secretion products in melanoma, considering its contribution to tumour progression, invasion, metastasis, recurrences, and resistance to classical therapy. Furthermore, the influences of the specific tumour microenvironment or "inflammasome", its association with adipose tissue products, including the release of "extracellular vesicles", and distinct microbiota are currently studied, considering their influences on diagnosis and prognosis. An insight into melanoma's particular features may reveal new molecular pathways which may be exploited in order to develop innovative therapeutic approaches or tailored therapy.

Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.