Grading of glioma tumors using digital holographic microscopy.

Gliomas are the most common type of cerebral tumors; they occur with increasing incidence in the last decade and have a high rate of mortality. For efficient treatment, fast accurate diagnostic and grading of tumors are imperative. Presently, the grading of tumors is established by histopathological evaluation, which is a time-consuming procedure and relies on the pathologists' experience. Here we propose a supervised machine learning procedure for tumor grading which uses quantitative phase images of unstained tissue samples acquired by digital holographic microscopy. The algorithm is using an extensive set of statistical and texture parameters computed from these images. The procedure has been able to classify six classes of images (normal tissue and five glioma subtypes) and to distinguish between gliomas types from grades II to IV (with the highest sensitivity and specificity for grade II astrocytoma and grade III oligodendroglioma and very good scores in recognizing grade III anaplastic astrocytoma and grade IV glioblastoma). The procedure bolsters clinical diagnostic accuracy, offering a swift and reliable means of tumor characterization and grading, ultimately the enhancing treatment decision-making process.

Metabolic reprogramming of immune cells by mitochondrial division inhibitor-1 to prevent post-vascular injury neointimal hyperplasia.

BACKGROUND AND AIMS: New treatments are needed to prevent neointimal hyperplasia that contributes to post-angioplasty and stent restenosis in patients with coronary artery disease (CAD) and peripheral arterial disease (PAD). We investigated whether modulating mitochondrial function using mitochondrial division inhibitor-1 (Mdivi-1) could reduce post-vascular injury neointimal hyperplasia by metabolic reprogramming of macrophages from a pro-inflammatory to anti-inflammatory phenotype. METHODS AND RESULTS: In vivo Mdivi-1 treatment of Apoe-/- mice fed a high-fat diet and subjected to carotid-wire injury decreased neointimal hyperplasia by 68%, reduced numbers of plaque vascular smooth muscle cells and pro-inflammatory M1-like macrophages, and decreased plaque inflammation, endothelial activation, and apoptosis, when compared to control. Mdivi-1 treatment of human THP-1 macrophages shifted polarization from a pro-inflammatory M1-like to an anti-inflammatory M2-like phenotype, reduced monocyte chemotaxis and migration to CCL2 and macrophage colony stimulating factor (M-CSF) and decreased secretion of pro-inflammatory mediators. Finally, treatment of pro-inflammatory M1-type-macrophages with Mdivi-1 metabolically reprogrammed them to an anti-inflammatory M2-like phenotype by inhibiting oxidative phosphorylation and attenuating the increase in succinate levels and correcting the decreased levels of arginine and citrulline. CONCLUSIONS: We report that treatment with Mdivi-1 inhibits post-vascular injury neointimal hyperplasia by metabolic reprogramming macrophages towards an anti-inflammatory phenotype thereby highlighting the therapeutic potential of Mdivi-1 for preventing neointimal hyperplasia and restenosis following angioplasty and stenting in CAD and PAD patients.

The Impact of Infections on the Progression of Chronic Kidney Disease.

Background and Objective: Infectious diseases continue to be a global burden and their impact is even worse if the patients already have other comorbidities. Because chronic kidney disease is very frequent, affecting 10% of the population, our study aims to explore the impact that infectious events have on its progression. Material and Methods: This is a retrospective, observational study based on a cohort of 238 dialyzed patients from the Nephrology Clinic of "Dr. Carol Davila" Clinical Hospital of Nephrology, Bucharest, who were followed from their first visit for five years, between 1 January 2007 and 1 January 2022. For each of them, the presence of an infectious event and the moment of the initiation of dialysis were recorded. Results: Statistical analysis showed that the patients who had at least one infectious episode were older (p = 0.004), their hemoglobin and lymphocytes were significantly lower (p = 0.03 and p = 0.02, respectively) and the time until the initiation of dialysis was lower (p = 0.007). Also, the preservation of kidney function was influenced by the number and the severity of infectious episodes. In the univariate Cox model, the following variables were associated with increased risk of dialysis: advanced age (p: 0.009; HR: 1.021; CI: 1.005 to 1.036), low hemoglobin (p: 0.001; HR: 0.861; CI: 0.786 to 0.943), previous diagnosis of chronic obstructive pulmonary disease (p: 0.002; HR: 2.467; CI: 1.376 to 4.424), presence of hematuria (p: 0.03; HR: 1.604; CI: 1.047 to 2.457) and increased values of proteinuria (p: 0.01; HR: 1.122; CI: 1.028 to 1.224) and of serum creatinine measured both at the time of the first visit and at the time of each infectious event (p: <0.001; HR: 1.262; CI: 1.141 to 1.396). Also, the presence of an infectious episode was associated with a 1.7-fold increase in the risk of dialysis initiation. The independent predictors of survival identified by the multivariate Cox model were age (p: 0.004; HR: 1.034; CI: 1.010-1.058), serum creatinine (p: <0.001; HR: 1.421; CI: 1.203 to 1.658) and proteinuria (p: <0.001; HR: 1.241; CI: 1.126 to 1.369) at the time of enrollment, but also the presence of an infectious episode during the patient's evolution (p: 0.04; HR: 1.705; CI: 1.013 to 2.868). Conclusions: In the evolution of patients with chronic kidney disease, an active search for individual factors favoring the occurrence of infectious episodes should be taken into consideration to prevent a faster progression toward end-stage kidney disease.

Current Therapeutic Approaches in Cervical Cancer Based on the Stage of the Disease: Is There Room for Improvement?

Cervical cancer continues to be among the most common malignancies in women, and in recent decades, important measures have been taken to reduce its incidence. The first and most important steps to achieve this goal are oriented toward prevention through screening programs and vaccination, mainly against oncogenic human papillomavirus (HPV) strains 16 and 18. The therapeutic approach is based on the diagnosis and treatment guidelines for cervical cancer, which establish for each stage (FIGO, TNM) specific conduct. These guidelines summarize quite precisely the elements of therapeutic practice, but, in some places, they leave optional variants based on which nuanced approaches could be established. Adherence to these guidelines, which include the performing of minor or major surgery, with or without chemotherapy and radiation therapy, combined with advanced imaging investigations, has been able to lead to a substantial increase in survival. The purpose of this literature review is to discuss the diagnosis and treatment options in cervical cancer depending on the histological type, FIGO staging, and patient performance index, taking into account the hospital resources available in middle-income countries (percentage of gross domestic product allocated to health services around 5.5%, in the case of Romania).