Combining Molecular and Traditional Prognostic Factors: A Holistic Approach to Breast Cancer Prognostication.

Breast cancer is a heterogeneous disease with various morphologies and molecular features, and it is the second leading cause of cancer death in women in developed countries. According to the literature, we currently lack both prognostic biomarkers and therapeutic targets. The most important prognostic factors are disease stage and Nottingham grade. We conducted a retrospective analysis involving 273 patients with BC who underwent neoadjuvant therapy before proceeding to curative surgical treatment between 1 January 2014 and 31 December 2023. Pathological procedures were conducted at the Department of Pathology, Emergency County Hospital of Targu Mureș, Romania. A statistical analysis was performed. Regarding the relationship between Nottingham grade and Ki67, grade I was associated with a Ki67 of less than 14. The relationship between tumor grade and luminal was similar (p = 0.0001): Grade I was associated with luminal A. Regarding TNM stage, it was statistically significantly correlated with TILs (p = 0.01) and RCB (p = 0.0001). Stages III and IV were associated with a high RCB and poor prognosis. Regarding the prognostic value, Nottingham grade 3 and TNM stages III and IV were correlated with low overall survival and disease-free survival, with poor prognosis, and, among the molecular variables, RCB played the most important prognostic role.

Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions.

Preeclampsia (PE) is a hypertensive disorder in pregnancy associated with significant fetal and maternal complications. Antiphospholipid syndrome (APS) is an acquired form of thrombophilia characterized by recurrent venous or arterial thrombosis and obstetric complications that significantly increases morbidity and mortality rates. While preeclampsia may not be the most prevalent obstetric complication in APS, it significantly impacts the long-term health of both mother and child. The treatment of preeclampsia in antiphospholipid syndrome is different from the treatment of preeclampsia as an independent disease. Despite current treatments involving anticoagulants, antiplatelet agents, and antihypertensive drugs, obstetric complications may persist, underscoring the need for cohesive management and effective treatments. The objective of our review is to briefly present knowledge about the physiopathology of preeclampsia and the role of antiphospholipid antibodies in this process. Based on the existing literature, our review aims to identify future directions in molecular pathology toward the discovery of biomarkers and targeted treatments. The application of multidisciplinary approaches and prognostic models, including new biomarkers, could be beneficial in the prediction of PE.

Shared Pathogenic and Therapeutic Characteristics of Endometriosis, Adenomyosis, and Endometrial Cancer: A Comprehensive Literature Review.

Endometriosis and adenomyosis behave similarly to cancer. No current treatments represent a cure, even if there are several options, including hormonal and surgical therapy. In advanced or recurrent pathologies, however, personalized treatment is necessary. We have found that due to the multiple common features, various therapeutic options have been used or studied for all three pathologies, with varying results. The objective of this review is to extract from the relevant literature the compounds that are used for endometriosis and adenomyosis characterized by malignant behavior, with some of these drugs being studied first in the treatment of endometrial cancer. Special attention is needed in the pathogenesis of these pathologies. Despite the multiple drugs that have been tested, only a few of them have been introduced into clinical practice. An unmet need is the cure of these diseases. Long-time treatment is necessary because symptoms persist, and surgery is often followed by postoperative recurrence. We emphasize the need for new, effective, long-term treatments based on pathogeny while considering their adverse effects.

Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature.

Endometriosis is a chronic inflammatory disease, which explains the pain that such patients report. Currently, we are faced with ineffective, non-invasive diagnostic methods and treatments that come with multiple side effects and high recurrence rates for both the disease and pain. These are the reasons why we are exploring the possibility of the involvement of pro-inflammatory and anti-inflammatory molecules in the process of the appearance of endometriosis. Cytokines play an important role in the progression of endometriosis, influencing cell proliferation and differentiation. Pro-inflammatory molecules are found in intrafollicular fluid. They have an impact on the number of mature and optimal-quality oocytes. Endometriosis affects fertility, and the involvement of endometriosis in embryo transfer during in vitro fertilization (IVF) is being investigated in several studies. Furthermore, the reciprocal influence between anti-inflammatory and pro-inflammatory cytokines and their role in the pathogenesis of endometriosis has been assessed. Today, we can affirm that pro-inflammatory and anti-inflammatory cytokines play roles in survival, growth, differentiation, invasion, angiogenesis, and immune escape, which provides a perspective for approaching future clinical implications and can be used as biomarkers or therapy.

Exploring Patient Adherence to Post-Surgical Follow-Up in Pelvic Endometriosis.

Endometriosis is a significant cause of disability that affects 5-10% of reproductive-aged women. Laparoscopy with histological confirmation is the gold standard in establishing the diagnosis as therapeutic management surgery is addressed to a certain category of patients. The objective of this study was to assess patient adherence to follow-up after surgery for endometriosis as the primary endpoint, pain symptoms, quality of life, mental health, and fertility as the secondary endpoints. We have analyzed patients' adherence to follow-up after surgery for endometriosis after 1, 3, 5, and 7 years. Out of the 2538 total number of surgeries, 453 patients replied just to the first questionnaire (group A), 528 to the first and second (group B), and only 356 carried out the entire follow-up schedule. General health was significantly lower for group A (46.6 vs. 56.4) but with no statistical difference in the post-surgical improvement in both groups. Pain level score improvement was lower for group A (10.5 vs. 18.8), which is statistically significant. In this light, laparoscopy still remains the gold standard in diagnosis only. Furthermore, no malignancy was discovered. The mental component was improved by laparoscopy based on SF-36 in group B. Studies on patient preference for surgery versus alternative treatment are needed.

Adenomyosis and Its Possible Malignancy: A Review of the Literature.

Cancer arising from adenomyosis is very rare, with transformation occurring in only 1% of cases and in older individuals. Adenomyosis, endometriosis and cancers may share a common pathogenic mechanism that includes hormonal factors, genetic predisposition, growth factors, inflammation, immune system dysregulation, environmental factors and oxidative stress. Endometriosis and adenomyosis both exhibit malignant behaviour. The most common risk factor for malignant transformation is prolonged exposure to oestrogens. The golden standard for diagnosis is histopathology. Colman and Rosenthal emphasised the most important characteristics in adenomyosis-associated cancer. Kumar and Anderson emphasised the importance of demonstrating a transition between benign and malignant endometrial glands in cancer arising from adenomyosis. As it is very rare, it is difficult to standardize treatment. In this manuscript, we try to emphasize some aspects regarding the management strategy, as well as how heterogenous the studies from the literature are in terms of prognosis in both cancers that develop from adenomyosis or those that are only associated with adenomyosis. The pathogenic mechanisms of transformation remain unclear. As these types of cancer are so rare, there is no standardised treatment. A novel target in the diagnosis and treatment of gynaecological malignancies associated with adenomyosis is also being studied for the development of new therapeutic concepts.

Immature Teratoma: Diagnosis and Management-A Review of the Literature.

An immature teratoma is a germinal malignant tumor composed of three germ cell layers, occurring more frequently in young women. It is the second most frequent among the malignant germinal tumors after dysgerminoma, and it is the only neoplasm with germ cells that are histologically graded. Even if we do not have a consensus regarding its therapeutical management, it has a good prognosis, with an excellent overall survival rate and good fertility preservation. More studies are needed regarding the necessity of adjuvant chemotherapy in pediatric oncology, and because of chemotherapy's long-term adverse effects, surveillance or a targeted treatment is preferred, but the main therapy is fertility-sparing surgery. Special attention should be given to the genetic mapping of the histological pieces for patient risk stratification due to its value in prognosis and future treatment.

The Approach of Artificial Intelligence in Neuroendocrine Carcinomas of the Breast: A Next Step towards Precision Pathology?-A Case Report and Review of the Literature.

Primary neuroendocrine tumors (NETs) of the breast are considered a rare and undervalued subtype of breast carcinoma that occur mainly in postmenopausal women and are graded as G1 or G2 NETs or an invasive neuroendocrine carcinoma (NEC) (small cell or large cell). To establish a final diagnosis of breast carcinoma with neuroendocrine differentiation, it is essential to perform an immunohistochemical profile of the tumor, using antibodies against synaptophysin or chromogranin, as well as the MIB-1 proliferation index, one of the most controversial markers in breast pathology regarding its methodology in current clinical practice. A standardization error between institutions and pathologists regarding the evaluation of the MIB-1 proliferation index is present. Another challenge refers to the counting process of MIB-1's expressiveness, which is known as a time-consuming process. The involvement of AI (artificial intelligence) automated systems could be a solution for diagnosing early stages, as well. We present the case of a post-menopausal 79-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). The purpose of this paper is to expose the interpretation of MIB-1 expression in our patient' s case of breast neuroendocrine carcinoma, assisted by artificial intelligence (AI) software (HALO-IndicaLabs), and to analyze the associations between MIB-1 and common histopathological parameters.

The Importance of Immunohistochemistry in the Evaluation of Tumor Depth of Primary Cutaneous Melanoma.

Primary cutaneous melanoma (PCM) is the most aggressive skin malignancy, with an increasing incidence and significant mortality. Tumoral invasion, expressed as Breslow thickness, is routinely assessed on hematoxylin and eosin (HE), although this stain may sometimes underestimate the tumoral depth. The aim of this study was to compare the efficiency of the immunohistochemical (IHC) markers S-100, SOX10, Melan-A, and HMB-45 with HE for the evaluation of the Breslow thickness and staging of PCM. This retrospective study included 46 cases of PCM diagnosed between 2015 and 2022; for each case, the Breslow thickness using HE, S-100, SOX10, Melan-A, and HMB-45 was measured and the appropriate T category was recorded. The highest values of the Breslow thickness were observed for S-100. However, S-100, SOX10, and Melan-A provided statistically significant higher values of the Breslow thickness compared to HE, but no difference was noted between HMB-45 and HE. S-100 was most frequently involved in increasing the T category (26.1%), the majority of cases being upstaged from T1a to T1b. The IHC markers S-100, SOX10, and Melan-A contributed to better evaluation of the melanoma invasion, especially in thin melanomas, but their impact on staging and consecutive treatment remains to be confirmed by future studies.

Electroanalysis of Naringin at Electroactivated Pencil Graphite Electrode for the Assessment of Polyphenolics with Intermediate Antioxidant Power.

A simple and rapid differential pulse voltammetric (DPV) method using a single-use electroactivated pencil graphite electrode (PGE*) is proposed for the rapid screening of the total content of polyphenolics (TCP) with intermediate antioxidant power (AOP) in grapefruit peel and fresh juice. The results were compared and correlated with those provided by the HPLC-DAD-MS method. NG voltammetric behavior at PGE* was studied by cyclic voltammetry and an oxidation mechanism was suggested. The experimental conditions (type of PGE, electroactivation procedure, pH, nature and concentration of supporting electrolyte) for NG DPV determination were optimized. The NG peak current varied linearly with the concentration in the ranges 1.40 × 10-6-2.00 × 10-5 and 2.00 × 10-5-1.40 × 10-4 mol/L NG and a limit of detection (LoD) of 6.02 × 10-7 mol/L NG was attained. The method repeatability expressed as relative standard deviation was 7.62% for the concentration level of 2.00 × 10-6 mol/L NG. After accumulation for 240 s of NG at PGE* the LoD was lowered to 1.35 × 10-7 mol/L NG, the linear range being 6.00 × 10-7-8.00 × 10-6 mol/L NG. The developed electrochemical system was successfully tested on real samples and proved to be a cost-effective tool for the simple estimation of the TCP with intermediate AOP in citrus fruits.

Diagnosis and Management of Dysgerminomas with a Brief Summary of Primitive Germ Cell Tumors.

Dysgerminoma represents a rare malignant tumor composed of germ cells, originally from the embryonic gonads. Regarding its incidence, we do not have precise data due to its rarity. Dysgerminoma occurs at a fertile age. The preferred treatment is the surgical removal of the tumor succeeded by the preservation of fertility. Even if a multidisciplinary team, founded in 2009 by a gynecologist, an oncologist, a pediatric oncologist and a pediatric surgeon, under the guidance of the Malignant Germ Cell International Consortium (MaGIC), studies this type of tumor, issues still remain related to the lack of a randomized study and to both the management and understanding of the concept of OMGCTs (ovarian malignant germ cell tumors). The aim of this review is to present from the literature the various approaches for this type of tumor, and, regarding innovative therapies or possible prevention, which can be applied in clinical practice. Multidisciplinarity and treatment in reference centers have proven their usefulness as well.

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study.

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most frequently occurring types of cancer in humans. Scientometric research is an innovative method for analyzing the research trends in various domains, with great implications in the field of medicine. Materials and Methods: We searched the Web of Science database with the following established query terms: "Squamous cell carcinoma", "skin", and "immunohistochemistry". After applying the inclusion and exclusion criteria, a total of 76 articles were selected. The present study aims to analyze, based on the frequency of use of keywords with scientometric algorithms and map-based distributions, the trends of the research concerning cSCCs in 2017-2022. Results: A graphical representation based on 11 scientometric maps presented the division of the keywords into seven clusters, from which seven categories of research interest were defined. The clusters represent a multidisciplinary approach to the diagnosis and treatment of cSCCs, cancer diagnostics, patient outcomes, histopathological importance, management of cSCCs, role of progression, and adequate treatment of and importance of immunohistochemistry for cSCCs. The distribution of the citations shows the importance of the available research on cSCCs by analyzing the first five most-cited articles included in our study in direct concordance with the seven defined clusters. Conclusion: The scientometric research method reveals the interest of research in the multidisciplinary approach used to obtain the best outcomes for the patient, including a targeted investigation, as well as diagnostic and treatment options. The trends in the research reveal that histopathological diagnostics and immunohistochemistry, combined with molecular techniques, are the most important tools used to establish a personalized diagnosis, thus increasing the quality of life and life expectancy for patients with cSCCs.

Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study.

Melanoma is the most aggressive melanocytic tumor whose incidence is continuously increasing worldwide. METHODS: We highlight the morphological, immunohistochemistry, and particularities of various melanoma types based on the cases diagnosed in our department from 2017 to 2021. RESULTS: We present 100 melanoma cases and one capsular nevus case. The most common type was nodular melanoma. The immunohistochemistry markers used were SRY-box transcription factor 10 (SOX10), S100 protein, human melanoma black 45 (HMB45), and melanoma antigen recognized by T cells 1 (Melan-A). Uveal melanoma and conjunctival melanoma represent particular tumors with independent prognostic factors. Uveal melanoma requires assessment of macrophages, microvascularisation, and mitoses. Sentinel lymph node metastases are essential targets that provide staging tools. Conjunctival melanoma and capsular nevi are diagnostic pitfalls. CONCLUSION: Melanoma can appear in various forms, and sometimes the diagnosis might be unclear. Today, immunohistochemistry remains the most important tool in confirming the diagnosis and prognosis for this type of neoplasia.

An Interesting Image of Transmural Migration of a Levonorgestrel-Releasing Intrauterine Device (LNg-IUD).

Intrauterine devices (IUDs) are very common as a method of birth control. By adding progesterone (levonorgestrel), a decrease in the risk of complications has been documented, including the risk of perforation. Even though only a few complications have been described, adjacent organs may be involved in the case of migration-a life-threatening situation. A 45-year-old G4P2 woman was seen in our clinic for LNg-IUD removal, according to the medical instructions. Her main complaints were abdominal discomfort, low back pain, and recurrent menorrhagia. A "lost" IUD was initially suspected; the patient confirmed the detection and removal of the control strings, and a subsequent discussion related to delayed transmural migration of the IUD being followed. The ultrasonography revealed the migration of the IUD to the uterine cervix and size-decreased uterine fibroids, confirming the effectiveness of the LNg-IUD. The MRI and ultrasonography being useless, a subsequent X-ray and CT scan were requested, both confirming a myometrium-positioned IUD, adjacent to the serosa and lumbosacral plexus. Even though the IUD is considered a safe device with reversible effect, it can be associated with severe morbidity, with an ultrasound follow-up being required. For more precise detection of the IUD, we strongly recommend an X-ray or CT scan examination, followed by safe removal.

Aspects of Tertiary Prevention in Patients with Primary Open Angle Glaucoma.

The purpose of the study is to assess the health of patients in the activity of tertiary prevention dedicated to preventing blindness caused by POAG (primary glaucoma with open angle and high tension) and NTG (primary glaucoma with open-angle and statistically normal tension-particular form of glaucoma with open angle) and preservation of the remaining visual function. The design of the study is epidemiological, observational, descriptive and retrospective, and uses only the data recorded in the existing records in the archives of the Ophthalmology office within the Integrated Outpatient Clinic of the Emergency Clinical Hospital of Oradea (IOCECHO) during the years 1999-2019 (anamnestic data; objective examination and paraclinical examination: intraocular pressure-IOP and visual field-VF). The methods of the study included the standardized protocol: anamnesis, physical ophthalmological examination, IOP determination, and computerized perimetry with the "Fast Threshold" strategy performed with the "Opto AP-300" perimeter. The obtained results were statistically processed with a specialized software (S.P.S.S.-I.B.M. Statistics version 22). The study examined the available data of 522 patients of which 140 were men (26.8%) and 382 were women (73.2%). The gender ratio was 0.37. In the period 1999-2019, 150,844 people with ophthalmic pathology were consulted in the Ophthalmology office of IOCECHO out of which 522 patients (0.35%) were diagnosed with primitive open-angle glaucoma, 184 people (35.2%) presented high IOP (POAG), and 338 people (64.8%) had statistically normal IOP (NTG). The annual proportion of cases diagnosed with glaucoma in the total number of patients examined was between 0.1% (2005; 2008; 2010) and 2.4% in 2012, when 101 people were detected. In the studied records, no cases of uni- and/or bilateral blindness were mentioned. The mean age of glaucoma patients at the first consultation was 60.81 ± 12.14 years with high frequencies in the 55-69 age groups and at the last consultation it was 66.10 ± 12.47 years with high frequencies in the age groups between 60-74 years. Monitoring and treatment of glaucoma patients was beneficial; IOP decreased statistically significantly: in patients with POAG by 46.16%, from 30.50 ± 7.98 mmHg to 16.42 ± 3.01 mmHg (p = 0.000) and in those with NTG by 17.44%, at 16.39 ± 3.66 mmHg at 13.53 ± 1.92 mmHG (p = 0.000). The duration of treatment and monitoring was on average 5.1 ± 3.4 years, for 184 patients (35.2%) with POAG and 5.1 ± 3.8 years for 338 patients (64.8%) with NTG. Tertiary prevention of glaucoma, by providing specialized care, ensures effective control of IOP and implicitly of the long-term evolution of the disease. IOP is the only modifiable risk factor in patients with POAG and NTG and its decrease prevents the progression of the disease and emphasizes the importance of early diagnosis and treatment. The management of the glaucoma patient consisted of: complete ophthalmological examination (subjective and objective), paraclinical examination with IOP, and VF measurement (valuable ophthalmological diagnostic tool) for disease detection and effective assessment of disease progression in order to improve the process of therapeutic decision making.

Differences between Active and Semi-Active Students Regarding the Parameters of Body Composition Using Bioimpedance and Magnetic Bioresonance Technologies.

The aim of the study was to identify differences in obesity-related parameters between active sports students and semi-active or sedentary students, differentiated by sex, in order to optimize health. The study sample included 286 students, of which the male experimental sample consisted of 86 active sports students, age X ± SD 21.25 ± 0.32 years; height X ± SD 181.08 ± 3.52 cm; control group consisting of 89 semi-active students aged X ± SD 21.07 ± 0.1.13 years; height X ± SD 182.11 ± 1.32. The female experimental sample includes 57 active sports students, age X ± SD 21.02 ± 0.92 years; height X ± SD 167.48 ± 1.34 cm; the control group includes 54 semi-active students aged X ± SD 21.57 ± 0.1.98 years; height X ± SD 168.42 ± 1.76. The study used a thalliometer, Tanita Health Ware software and Quantum Resonance Magnetic Analyzer equipment to investigate height (cm), Body Mass Index (BMI), muscle mass (kg, %), as well as the obesity analysis report, and componential analysis of body and nourishment. The differences registered between the samples of active and semi-active sports subjects were predominantly statistically significant for p < 0.05. The differences registered between the samples of active and semi-active sports subjects were predominantly statistically significant for p < 0.05. The most important parameters regarding obesity and body composition that registered significant differences between the two male groups were in favor of the group of active athletes: triglyceride content of abnormal coefficient 0.844 (CI95% 0.590-1.099), abnormal lipid metabolism coefficient 0.798 (CI95% 1.091-0.504), obesity degree of body (ODB %) 10.290 (CI95% 6.610-13.970), BMI 2.326 (CI95% 1.527-3.126), body fat (kg) 2.042 (CI95% 0.918-3.166), muscle volume (kg) 2.565 (CI95% 1.100-4.031), Lean body weight (kg) 2.841 (CI95% 5.265-0.418). In the case of female samples, the group of active sportswomen registered the biggest differences compared to the group of students who were significantly active in the parameters: abnormal lipid metabolism coefficient 1.063 (CI95% 1.380-0.746), triglyceride content of abnormal coefficient 0.807 (CI95% 0.437-1.178), obesity degree of body (ODB%) 8.082 (CI95% 2.983-13.181), BMI 2.285 (CI95% 1.247-3.324), body fat (kg) 2.586 (CI95% 0.905-4.267), muscle volume (kg) 2.570 (CI95% 0.154-4.985), lean body weight (kg) 4.118 (CI95% 1.160-7.077). The results of the study directly facilitate the understanding of the complexity of the impact of obesity on multiple parameters of body composition and health.

The Motor Impact of the Static Balance in the Up Plank Position on Three Different Balls in Physical Activities of Physical Education Students.

The present study aimed to assess the capacity of stability and motor impact in the development of the balance of student athletes by reducing the support surface on the ball in the up plank position, by using three categories of balls of equal size, but with different elasticity and weight. In this study, the second aim was to investigate the differences in maintaining static balance, on different balls, between those who are practicing individual sports or team sports. The total study sample include 48 students, active athletes (45.8% of individual sports and 54.2% of team sports), age X ± SD 18.74 ± 1.94 years. The research included two test sessions (initial and final) applied in two stages. The static balance tests were performed by measuring the time maintaining the up plank position with two and three points of support on the three balls, with different characteristics of elasticity and ranges of deformation: medical ball, handball ball and fitness ball. The results of the study showed that the superior initial and final results were recorded on the fitness ball, and the inferior results on the medicine ball. The upper difference was recorded at the up plank position with two support points (arms, legs) on the fitness ball, at 4980 s, and the lowest in the same test on the medical ball, at 3420 s. The largest difference was recorded at the up plank position with three support points on the handball ball, at 7.082 s, and the lowest in the same test on the medical ball, at 3.093 s. The subjects of the study perceived that the most difficult position to execute was the up plank position on the medical ball with two support points, with 43.8%, and the easiest stability was registered in the up plank position on the fitness ball with three points of support, of 37.5%. The relevance of the research results from the possibility of using different balls in conditions of positioning and body posture with a diminished support base in order to improve physical fitness.

Month of birth, a risk factor for violent behaviour in suicidal patients admitted in emergency?

Although there are numerous publications on the existing link between month of birth and suicide, only two studies focus on suicide attempts and auto-aggressive behavior. Research data suggest that month of birth is related to a variation of 5-HIAA in the cerebrospinal fluid, which correlates with violent behavior (VB). Therefore, the aim of this study is to search, for the first time, for a possible link between month of birth and the occurrence of VB in emergency, for patients admitted for a suicide attempt with medication. This is a 10 months prospective study among all the patients of the canton of Geneva, Switzerland, admitted in emergency for a suicide attempt with medication. During a 10 months study period we included 493 patients, of which 77 (15.62%) presented VB. Higher incidence of VB was found in subjects where born at the end of winter and the beginning of spring, with a maximum for April and a minimum for December. In spite of a relatively small number of subjects, it seems promising to study the occurrence of VB as a function of month of birth in patients admitted in emergency for a suicide attempt.