Georgeta Camelia Cozaru

Background/Objectives: Inherited thrombophilia (IT) has been extensively investigated as a potential contributor to adverse pregnancy outcomes; however, reported prevalence varies widely across studies. This systematic review aimed to evaluate how cohort selection influences the reported prevalence of inherited thrombophilia in pregnancy and to explore the implications of this variability for clinical interpretation and screening practices. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Google Scholar were searched. A total of 5480 records were identified, and 7 observational studies (cohort and case–control) met inclusion criteria. Data were synthesized qualitatively due to heterogeneity. Results: Prevalence ranged from 0% to 14%, depending on population characteristics. The largest cohort study reported an inherited thrombophilia prevalence of 8.1%, comparable to the general population. Higher rates were observed in referral-based and antiphospholipid Syndrome (APS)-associated cohorts, while case–control studies showed no significant differences between affected individuals and controls. Ethnic variability was also observed. Conclusions: These findings should be interpreted as patterns observed across heterogeneous study designs rather than as definitive evidence of causality. Current evidence does not clearly support universal screening in pregnancy; however, the findings should be interpreted cautiously because several included studies were limited by small sample sizes and methodological heterogeneity.

Biomarker discovery in sarcoidosis mechanisms represents an innovative research tool. Inflammatory responses in sarcoidosis patients were analyzed by flow cytometry to highlight CD8a+CD45+, CD45+CD8a−, CD4+CD19+, CD4+CD19−, CD3+CD56+CD16+, CD56+CD16+, and CD16+CD56− as predictive biomarkers. In our study, monocyte-derived macrophage activation (M1 phenotype), represented by CD8a+CD45+ expression, is characteristic of granulomatous inflammation in active and progressive sarcoidosis and serves as a biomarker with very good accuracy and high specificity for establishing a diagnosis of sarcoidosis. As a prognostic biomarker, it is an independent predictive factor of disease progression, being negatively associated with applied treatments by sarcoidosis stage. The accumulation of activated CD4+ T-helper cells in sarcoid granulomas is responsible for the establishment of a pro-inflammatory phenotype and serves as a biomarker with good accuracy and high specificity for sarcoidosis diagnosis. As a prognostic biomarker, CD3+CD56+CD16+ (iNKT) is an independent predictor associated negatively with disease progression, being positively correlated with treatment applied by sarcoidosis stage. CD biomarker analysis, yielding predictive models with specificity for diagnosis and prognosis, is an important research tool for estimating disease progression in patients with different inflammatory response phenotypes across the stages of sarcoidosis.

Background/Objectives: Inflammatory bowel disease (IBD) and Parkinson’s disease (PD) are chronic disorders affecting different organs, and evidence has proposed a bidirectional link between them. Fecal calprotectin, which reflects intestinal inflammation and gut barrier injury, is augmented in different neurodegenerative diseases, including PD. In this study, we aimed to investigate whether fecal calprotectin levels in PD increase independently of gastrointestinal inflammation and aging. Methods: Fecal calprotectin values were compared in two groups (PD and IBD) of 30 patients each, taking into consideration variables such as endoscopic aspects and age. Analyses of fecal calprotectin levels in PD patients show an increase with advancing age, which was not observed in the IBD cohort. Results: Most PD patients had fecal calprotectin values exceeding 200 μg/g (mean value 366.25 μg/g), and their levels were comparable to those of patients with inflammatory bowel disease (Ulcerative Colitis, Crohn’s Disease, mean value 537.70 μg/g). In the PD cohort, a weak positive association between calprotectin levels and inflammatory signs was observed, and in the IBD cohort, higher calprotectin levels were strongly associated with more severe endoscopic modifications. Conclusions: This weak but positive correlation with intestinal inflammation in PD patients suggests the involvement of complex mechanisms, other than those related to inflammaging or gut barrier injuries.

Background/Objectives: The diversity of the oral microbiota exerts its effects in maintaining dental and overall health. The unique genetic profile of each individual influences the composition of the oral microbiota, determining susceptibility to certain diseases. The aim is to observe its role by highlighting the pathogenic mechanisms involved in oral dysbiosis and identify genetic determinism’s influence in maintaining balance. Methods: This study was designed as a narrative review of the oral microbiota, utilizing some of the principles and guidelines of systematic review to increase methodological rigor. We examined 121 articles such as reviews, meta-analyses, editorials, and observational studies, which met the inclusion and exclusion criteria. The inclusion criteria for studies were as follows: (1) studies that evaluated the impact of the microbiota in oral or/and systemic diseases; (2) studies that observed pathogenic mechanisms in the oral microbiota; (3) studies that evaluated the interaction of the microbiota with the immune system (4); studies that evaluated genetic implications in the microbiota. Results: Host genes regulate inflammatory and immunological reactions that play a role in microbiological balance. This explains the increased resistance of some to diseases, including gingivitis or periodontitis. Also, the implications of oral dysbiosis are reflected not only locally, but also generally, being associated with various systemic conditions. Conclusions: Understanding the pathogenic mechanisms and genetic determinants involved in oral dysbiosis may help create individualized therapies for preventing and managing oral and systemic disorders. A healthy lifestyle and adequate oral hygiene can facilitate a diverse and balanced microbiome, crucial for overall health.

Background: Brain tumors pose a significant health threat, leading to high morbidity and mortality rates. Astrocytoma IDH-mutant grade 4 (A4_IDHmt) and glioblastoma IDH-wildtype (G4I_DHwt) exhibit similar clinical and imaging characteristics. This study aims to highlight the differences in their clinical evolution and histogenetic aspects with the possible therapeutic impact, as well as the adverse prognostic factors in patient survival. Methods: We performed a 10-year retrospective study of grade 4 gliomas, evaluating immunomarkers and FISH tests. We also quantified tumor necrosis and microvascular density. Results: A total of 81 cases were identified; 54.32% were A4_IDHmt. We observed that A4_IDHmt patients were younger (34.10% under 50) and had a higher survival rate (4.55%). This group also exhibited a more pronounced microvascular density (p = 0.010) and proliferative index (p = 0.026). G4_IDHwt was associated with larger tumor volumes (94.84 cm³ vs. 86.14 cm³), lower resectability rates (82.88% vs. 87.67%), and a more significant immature cell population (83.78% vs. 68.18%). In the case of both, the negative risk on survival in the univariate analysis is given by advanced age (A4_IDHmt: HR = 1.035, G4_IDHwt: HR = 1.045) and p53 immunopositivity (A4_IDHmt: HR = 6.962, G4_IDHwt: HR = 4.680). Conclusions: The negative risk factors for A4_IDHmt include the rapid onset of clinical symptoms (HR = 2.038), diabetes mellitus (HR = 2.311), arterial hypertension (HR = 2.325), residual tumor (HR = 2.662), increased residual tumor volume (HR = 1.060), increased microvascular density (HR = 1.096), and high tumor necrosis (HR = 1.097). For G4_IDHwt, the negative risk factors consist of increased residual volume (HR = 1.023), lost PTEN immunoreaction (HR = 33.133), and unmethylated DNA status (HR = 6.765, respectively HR = 20.573). Even if it has more risk factors, A4_IDHmt is the lesser evil.

Tumor heterogeneity results in aggressive cancer phenotypes with acquired resistance. However, combining chemical treatment with adjuvant therapies that cause cellular structure and function perturbations may diminish the ability of cancer cells to resist at chemical treatment and lead to a less aggressive cancer phenotype. Applied treatments on prostate hyperplasia primary cell cultures exerted their antitumor activities through mechanisms including cell cycle blockage, oxidative stress, and cell death induction by flow cytometry methods. A 5.37 mM Chloramphenicol dose acts on prostate hyperplasia cells by increasing the pro-oxidant status, inducing apoptosis, autophagy, and DNA damage, but without ROS changes. Adding 6.30 mM vitamin C or 622 µM vitamin E as a supplement to 859.33 µM Chloramphenicol dose in prostate hyperplasia cells determines a significant increase of ROS level for a part of cells. However, other cells remain refractory to initial ROS, with significant changes in apoptosis, autophagy, and cell cycle arrest in G0/G1 or G2/M. When the dose of Chloramphenicol was increased to 5.37 mM for 6.30 mM of vitamin C, prostate hyperplasia cells reacted by ROS level drastically decreased, cell cycle arrest in G2/M, active apoptosis, and autophagy. The pro-oxidant action of 1.51 mM Erythromycin dose in prostate hyperplasia cell cultures induces changes in the apoptosis mechanisms and cell cycle arrest in G0/G1. Addition of 6.30 mM vitamin C to 1.51 mM Erythromycin dose in hyperplasia cell cultures, the pro-oxidant status determines diminished caspase 3/7 mechanism activation, but ROS level presents similar changes as Chloramphenicol dose and cell cycle arrest in G2/M. Flow cytometric analysis of cell death, oxidative stress, and cell cycle are recommended as laboratory techniques in therapeutic and diagnostic fields.

Preterm births comprise all pregnancies coming to an end before the gestational age of 37 weeks and remain the leading cause of death in children under 5 years old despite efforts to reduce their occurrence. We aim to analyze all morbidity and mortality data to understand causes and risk factors, helping in prevention efforts. This study includes 140 cases collected during 2018–2022. Demographic, maternal, and thanatogenetic data were statistically analyzed. We observed an upward slope of stillborn babies. In the case of live-born premature, the average survival was 301.76 h. The multivariate analysis noted that extremely low birth weight (HR = 5.141) and very low birth weight (HR = 4.177) are risk factors involved in mortality. Increased parity was associated with premature births with low and very low birth weight (p = 0.019). We observed that a mother’s age of over 30 years is predictable for the development of pregnancy-induced hypertension. Cerebral and pulmonary hemorrhages were the most common intermediate morbid conditions, with prematurity and plurivisceral hemorrhages serving as their root causes. We have identified that anthropometric measurements have a high predictability on malformed babies. The identified associations indicate a shared mechanism for certain lesion processes, which can help optimize resources for predicting and preventing preterm neonatal issues.

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut–liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut–liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields.

Cutaneous melanoma is a public health problem. Efforts to reduce its incidence have failed, as it continues to increase. In recent years, many risk factors have been identified. Numerous diagnostic systems exist that greatly assist in early clinical diagnosis. The histopathological aspect illustrates the grim nature of these cancers. Currently, pathogenic pathways and the tumor microclimate are key to the development of therapeutic methods. Revolutionary therapies like targeted therapy and immune checkpoint inhibitors are starting to replace traditional therapeutic methods. Targeted therapy aims at a specific molecule in the pathogenic chain to block it, stopping cell growth and dissemination. The main function of immune checkpoint inhibitors is to boost cellular immunity in order to combat cancer cells. Unfortunately, these therapies have different rates of effectiveness and side effects, and cannot be applied to all patients. These shortcomings are the basis of increased incidence and mortality rates. This study covers all stages of the evolutionary sequence of melanoma. With all these data in front of us, we see the need for new research efforts directed at therapies that will bring greater benefits in terms of patient survival and prognosis, with fewer adverse effects.

(1) Background: Human cytomegalovirus (CMV) infection is one of the most frequent opportunistic infections in immunosuppressed patients. Romania has one of the highest incidences of patients living with human immunodeficiency virus (HIV) which determines an immunosuppressive state. The aim of this study was to establish the prevalence of CMV infection among women living with HIV in Southeastern Romania and also to evaluate and correlate antiretroviral therapy (ART) with CD4 level and CMV disease evolution. (2) Methods: Seventy women living with HIV from Southeastern Romania were screened for CMV infection using antigen quantification. Of these, 50 were included in the study. First, the patients filled out a questionnaire regarding social conditions and other associated diseases. Then, we explored the statistical correlations between the data and HIV status, CD4+ cell counts, viral load, and antiretroviral therapy (ART). (3) Results: Median age of the patients was 33 years. Twenty-nine cases were diagnosed with HIV after sexual life beginning and 21 before. Most of the patients had a CD4 level over 200 cells/µL. ART duration in the CD4 under 200 cells/µL group was a bit longer than that in the CD4 over 200 cells/µL group. Forty-one patients had undetectable viremia. CD4 average value in the lot of patients with undetectable viremia was 704.71 cells/µL and in the lot with detectable viremia was 452.44 cells/µL. Viremia values correlated negatively with CD4 level. A positive correlation between IgG CMV values and ART therapy length was identified. A negative significant correlation between values of IgG CMV and values of CD4 was identified. CD4 value correlated negatively with IgG CMV values and with CMV avidity. (4) Conclusions: IgG CMV values had a weak positive correlation with ART therapy length, and a negative statistically significant correlation with values of CD4. CMV avidity has a negative correlation with CD4 value.