Chemical Biomarkers of Diffusse Axonal Injury

Craniocerebral trauma is the most common cause of death and post-traumatic disability in people under 45 years of age. In Romania, the annual incidence shows, that for every 100,000 inhabitants, there are 300 cases of craniocerebral trauma that require specialized medical assistance. Craniocerebral traumas are the most common types of traumas encountered in current forensic practice. Research on the mechanisms of injury, the timing of head trauma and the establishment of causes of death remain relevant. Establishing the traumatic moment implies both the distinction between pre-mortem and post-mortem injuries but also considerations regarding the post-traumatic survival interval. Regarding the elucidation of the moment of occurrence of the craniocerebral trauma from the forensic point of view, a satisfactory result has not been reached so far. The classic hypothesis regarding the development of traumatic brain injuries shows that they are the result of primary traumatic injuries due to cell necrosis combined with the inflammatory brain response that causes secondary brain injuries. It was considered that post-traumatic neuronal losses are strictly due to necrosis and inflammation, and cellular apoptosis being a physiological process, does not play a role in this process. Due to recent experimental data, brain cell apoptosis has begun to be reevaluated. The pathophysiology of traumatic brain injury is far from being fully understood, with the idea that apoptosis would play an even more important role than originally thought. Specifically, damaged brain cells release neuromodulatory substances that can lead to late-onset neuronal damage long after necrotic and inflammatory brain phenomena have ceased to act. These neuronal cell losses are responsible for the development of various neurological deficits and post-traumatic sequelae.</p

ACTUALITĂŢI ÎN DIAGNOSTICUL ŞI TERAPIA HEPATOBLASTOMULUI PEDIATRIC CU METASTAZE PULMONARE

Deşi frecvenţa hepatoblastomului este redusă, acesta reprezintă cea mai comună tumoră hepatică primară ma lignă a copilului. Prognosticul bolii s-a îmbunătăţit considerabil în ultimele decenii, datorită progreselor terapeutice oncologice şi chirurgicale. Totuşi, tumorile aflate într-un stadiu avansat la momentul diagnosticului au în continuare un prognostic rezervat. Prezentăm cazul unui copil de 2 ani şi 9 luni, diagnosticat în februarie 2014 cu hepatoblastom, cu risc înalt (metastaze pulmonare), pentru care s-a intervenit chirurgical practicându-se ex cizia completă a tumorii. Ulterior, s-a iniţiat chimioterapie conform protocolului SIOPEL-4 modificat: astfel, blocurile de chimioterapie care ar fi trebuit administrate preoperator au fost utilizate postoperator. După finalizarea chimioterapiei, examenul CT toraco-abdominal efectuat în septembrie 2014 a indicat răspuns complet al bolii la tratament. Evaluarea periodică a pacientului a relevat până în prezent absenţa semnelor de recidivă locală tumorală, absenţa metastazelor şi un status de performanţă de 80 pe scala Lansky. Utilizarea terapiilor moleculare ţintite, a transplantului hepatic şi a unor noi chimioterapice poate reprezenta în viitor o modalitate de îmbunătăţire a prognosticului pacienţilor cu hepatoblastom cu risc înalt. De asemenea, modificarea pro tocoalelor de chimioterapie ar putea reprezenta o opţiune pentru îndeplinirea acestui scop

Real Check RIO: A Real-World Analysis of Nivolumab in First Line Metastatic Melanoma Assessing Efficacy, Safety and Predictive Factors

We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy on a treatment-naive population. After a median follow-up of 36 months, the median progression free survival (PFS) was 26 months (95% CI, 15–36) and the median overall survival (OS) was 31 months (95% CI, 20.1–41.8). At 12 months after the initiation of immunotherapy, the percentage of patients alive was 70%, and at 24 months 62.5%. The most common adverse events observed were dermatological (23.5%) and grade ≥3 was identified in 4 (6.8%) patients. Multivariate analysis indicated that the presence of liver metastases (HR 4.42; 95% CI: 1.88–10.4, p = 0.001) and a neutrophils/lymphocytes ratio (NLR) were associated with poor survival (HR 3.21; 95% CI: 1.04–9.87, p = 0.04). Although retrospective data on a small group of patients were analyzed, we can conclude that our results in RIO are similar to those described in clinical trials and other real-world studies. Our study highlights the potential usefulness of liver metastases and NLR as novel predictive factors in clinical decision-making

Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania

Mutations in RAS, BRAF, PIK3CA, and TP53 are well-established genetic abnormalities in metastatic colorectal cancer (mCRC). However, limited information is available for patients from Eastern Europe, including Romania. In this retrospective analysis, we investigated 104 mCRC patients from the Northeastern region of Romania to determine the frequency, distribution, coexistence, and clinicopathological and molecular correlations of these mutations. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). Patients with KRAS mutant tumors and wild-type TP53 genotype were found to have no personal history of gastrointestinal cancer (p = 0.02, p = 0.007). KRAS mutations in exon 3 were associated with the female gender (p = 0.02) and the absence of lymph node invasion (p = 0.02). PIK3CA mutations were linked to the absence of lymph node invasion (p = 0.006). TP53 mutations were associated with KRAS mutations in exon 2 (p = 0.006), ulcerated histopathologic type (p = 0.04), and G2 differentiation (p = 0.01). It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations

KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer – practical implications for the clinician

Colorectal cancer is a successful model of genetic biomarker development in oncology. Currently, several predictive or prognostic genetic alterations have been identified and are used in clinical practice. The RAS gene family, which includes KRAS and NRAS act as predictors for anti-epithelial growth factor receptor treatment (anti-EGFR), and it has been suggested that NRAS mutations also play a role in prognosis: patients harboring NRAS alterations have a significantly shorter survival compared to those with wild type tumours. BRAF V600E mutations are rare and occur mostly in tumors located in the ascending colon in elderly female patients. BRAF is instrumental in establishing prognosis: survival is shorter by 10–16 months in BRAF-mutant patients, and BRAF may be a negative prognostic factor for patients who undergo hepatic or pulmonary metastasectomy. Moreover, this mutation is used as a negative predictive factor for anti-EGFR therapies. Two new biomarkers have recently been added to the metastatic colorectal cancer panel: HER2 and microsatellite instability. While HER2 is still being investigated in different prospective studies in order to validate its prognostic role, microsatellite instability already guides clinical decisions in substituted with advanced colorectal cancer

Ischemia with Nonobstructive Coronary Artery Disease and Atrial Cardiomyopathy—Two Sides of the Same Story?

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies

Ischemia with Nonobstructive Coronary Artery Disease and Atrial Cardiomyopathy&mdash;Two Sides of the Same Story?

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies

Hair EDX Analysis—A Promising Tool for Micronutrient Status Evaluation of Patients with IBD?

Micronutrient deficiencies can arise in various conditions, including inflammatory bowel diseases (IBD), and diagnosing these deficiencies can be challenging in the absence of specific clinical signs. The aim of this study was to evaluate the status of various trace elements hair concentration in IBD patients compared to a healthy control group and to identify potential correlations between the micronutrient status and relevant parameters related to disease activity. The concentrations of iron, magnesium, calcium, zinc, copper, manganese, selenium and sulfur in the hair of 37 IBD patients with prior diagnosed IBD (12 Crohn’s disease and 25 ulcerative colitis) and 31 healthy controls were evaluated by Energy Dispersive X-Ray spectroscopy (EDX). Significant differences in hair concentration profile of studied trace elements were identified for IBD patients compared to healthy controls. A significantly decreased hair concentration of iron, magnesium, calcium and selenium and a significantly increased sulfur hair concentration were observed in IBD patients at the time of evaluation. A decreased hair calcium concentration (r = −0.772, p = 0.003) and an increased sulfur concentration (r = 0.585, p = 0.046) were significantly correlated with disease activity. Conclusion: Hair mineral and trace elements evaluation may contribute to a proper evaluation of their status in IBD patients and improving the management of nutritional status of IBD patients

The Intertwining Roads between Psychological Distress and Gut Microbiota in Inflammatory Bowel Disease

Inflammatory bowel disease represents one of the most life-altering gastrointestinal pathologies, with its multifactorial nature and unclear physiopathology. The most relevant clinical forms, ulcerative colitis and Crohn’s disease, clinically manifest with mild to severe flares and remission periods that alter the patient’s social, familial and professional integration. The chronic inflammatory activity of the intestinal wall determines severe modifications of the local environment, such as dysbiosis, enteric endocrine, nervous and immune system disruptions and intestinal wall permeability changes. These features are part of the gastrointestinal ecosystem that modulates the bottom-to-top signaling to the central nervous system, leading to a neurobiologic imbalance and clinical affective and/or behavioral symptoms. The gut-brain link is a bidirectional pathway and psychological distress can also affect the central nervous system, which will alter the top-to-bottom regulation, leading to possible functional digestive symptoms and local inflammatory responses. In the middle of this neuro-gastrointestinal system, the microbiome is a key player, as its activities offer basic functional support for both relays. The present article presents current scientific information that links the pathophysiology and clinical aspects of inflammatory bowel disease and psychiatric symptomatology through the complex mechanism of the gut-brain axis and the modulatory effects of the gut microbiota