Primary Central Nervous System Lymphoma

Although non-Hodgkin’s lymphoma (NHL) is a frequent cancer worldwide, primary central nervous system (CNS) lymphoma (PCNSL) is a rare presentation, with an incidence of less than 0.5 per 100,000 persons-years in the western world. In the vast majority of cases, it has the histology of a diffuse large B-cell lymphoma (DLBCL) and is a hardly curable disease with high relapse risk. Therapeutic options are limited by blood-brain barrier penetration of drugs and because of its low-incidence high-grade evidence from large studies is lacking, current management being based on reports on rather small cohorts. The current standard first-line treatment for PCNSL consists of high-dose methotrexate (HD-MTX) in combination with a variety of drugs and consolidation whole-brain radiotherapy, the latter being progressively replaced by chemotherapy. For patients relapsing after first-line treatment, intensive chemotherapy with autologous stem cell support is a feasible and relatively safe salvage therapy. In the present chapter, we briefly discuss primary central nervous system lymphoma management and review current therapeutic options and evidence-based recommendations. We discuss the role of whole-brain radiotherapy (WBRT) and new prospects to avoid this side effect-ridden approach. Also, we will look at new therapeutic approaches currently under investigation, including immunotherapy

The Ontogeny of Hippocampus-Dependent Memories

The formation of memories that contain information about the specific time and place of acquisition, which are commonly referred to as "autobiographical" or "episodic" memories, critically relies on the hippocampus and on a series of interconnected structures located in the medial temporal lobe of the mammalian brain. The observation that adults retain very few of these memories from the first years of their life has fueled a long-standing debate on whether infants can make the types of memories that in adults are processed by the hippocampus-dependent memory system, and whether the hippocampus is involved in learning and memory processes early in life. Recent evidence shows that, even at a time when its circuitry is not yet mature, the infant hippocampus is able to produce long-lasting memories. However, the ability to acquire and store such memories relies on molecular pathways and network-based activity dynamics different from the adult system, which mature with age. The mechanisms underlying the formation of hippocampus-dependent memories during infancy, and the role that experience exerts in promoting the maturation of the hippocampus-dependent memory system, remain to be understood. In this review, we discuss recent advances in our understanding of the ontogeny and the biological correlates of hippocampus-dependent memories

Stress-induced Perioperative Depressive Symptoms

Sustained stress has been correlated with increases in cortisol levels and decreased levels of brain transmitters including serotonin or dopamine. As a result of better understanding of human pathophysiology and pain physiology, the fields of surgery and anesthesia have seen major advances in the last years.However, a high percentage of patients develop depressive symptoms following major surgery and pathogenic perspective is very complex and require an holistic approach

Challenges Regarding the Performance of Public Investment Projects

Investments, approached as a factor influencing the future, have an essential role in economic growth and development by stimulating the production process and by creating new, high-performing structures that are correlated with the specific needs of individuals and society. From the point of view of access to resources, but also of economic-social competition, economic development generates a higher level of performance, certified on the basis of qualitative and quantitative evaluation processes. In this context, the analysis system of investment projects must be based on operational principles and instruments with medium and long-term impact, capable of aligning with strategic visions. In this paper, based on the research carried out in the specialized literature and the analyzed studies regarding public investments, we identify the current challenges regarding the performance of public investment projects and propose a series of criteria for evaluating the performance of public investments and a sequence of stages to ensure the elimination of non-performing projects at the local, regional and national level. The results of the present research reveal the inadequate prioritization of public investments to ensure adequate sustainability and offer us the opportunity to develop new research directions in the following works in which we will analyze the impact that inadequate prioritization has on the sustainability of local, regional and national communities

Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. Despite a relatively low prevalence, it accounts for a disproportionate number of thyroid cancer-related deaths, due to its resistance to any therapeutic approach. Here we describe the first mouse model of ATC, obtained by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion, and distant metastases. Expression profiling of the murine ATCs reveals a significant overlap with genes found deregulated in human ATC, including genes involved in mitosis control. Furthermore, similar to the human tumors, [Pten, p53]thyr−/− tumors and cells are highly glycolytic and remarkably sensitive to glycolysis inhibitors, which synergize with standard chemotherapy. Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer-A Multicentre Propensity-Score-Matched Retrospective Analysis

The sensitivity to chemotherapy of KRASG12C-mutated colorectal cancer has been investigated to verify whether the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care in the near future. To this aim, the present retrospective study was designed to assess the performance of irinotecan vs. oxaliplatin in the first-line treatment of KRASG12C-mutated mCRC patients and provide support for first-line decision making. In this setting of patients treated with FOLFIRI or FOLFOX +/ bevacizumab, irinotecan and oxaliplatin were compared using a propensity-score-matched analysis. the survival superiority of irinotecan was demonstrated over oxaliplatin in KRASG12C-mutated patients, while no differences were observed in a control cohort of KRASG12D-mutated patients. this should be considered when investigating chemotherapy plus targeted agent combinations.background: KRAS(G12C)-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRAS(G12C)inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. methods: a multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/ bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment-effect interactions. KRAS(G12D)-mutated patients were analysed as control. results: one hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. however, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. no difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). Conclusions: First-line irinotecan-based regimens provided better survival results in KRAS(G12C)-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations

Breef overview of gestational diabetes mellitus

As obesity increases worldwide, so do the incidence of gestational diabetes mellitus (GDM) and the related perinatal complications. Pancreatic β-cell secretion is altered by hormonal changes during pregnancy. It appears, however, that patients who develop gestational diabetes have pre-existing insulin resistance. However, there are other risk factors to be considered, such as obesity, age, ethnicity, and polycystic ovary syndrome. Screening for gestational diabetes is very important to avoid maternal and fetal complications. For most pregnant women, glycemic control is achieved through dietary and lifestyle changes, although a small percentage requires pharmacological treatment

Pregnancy in the context of Multiple Sclerosis

Multiple Sclerosis is a chronic autoimmune neurodegenerative disorder which affects brain, spinal cord and optic nerve. During last years the perception over the disease changed dramatically, now being considered a handleable disease. The particularity of this subject is that Multiple Sclerosis is a disease which affects mostly young women, many of them not having any children at the moment of diagnosis. This article highlights the fact that women diagnosed with Multiple Sclerosis are allowed to get pregnant, and, moreover, they are encouraged to live a normal life. In most cases, disease activity freezes during pregnancy, only a small percentage of women will continue to have clinically and radiologically active disease. For those women, IFN-β and Glatiramer Acetate are the first-choice therapies that should be given. In cases when the disease is not responding to common medication, refractory to treatment forms may be successfully treated with Natalizuab, during the first and the second trimester. Breastfeeding is also encouraged, as it has a protective effect on disease progression. The main purpose of this article is to make a literature review in which to summarize the updates regarding pregnancy and postpartum management, relapses management and, also, the impact of pregnancy on Multiple Sclerosis course. The analysis was limited to articles written in English and published between August 2019 - October 2022 on PubMed, NCBI and Medical Journals

Managing intrauterine growth restriction

The fetal growth normally depends on sufficient delivery of oxygen and nutrients mainly via the placenta. Inadequate fetal nutrition may result in poor development and adaptation that permanently alter the fetus' metabolism and physiology. Intrauterine Growth Restriction is defined as a deviation on the fetal growth pattern. An estimated fetal weight (EFW) that is below the 10th percentile for gestational age is commonly used to describe fetal growth restriction. Usually obtained sonographically, there is evidence that ultrasound imaging of the uterine artery, middle cerebral artery, and fetal umbilical artery during the late third-trimester (approximately 35-37 weeks) significantly improves the detection and diagnosis of IUGR. In obstetrics, an increased risk of perinatal mortality and morbidity is associated with the diagnosis of IUGR