New Molecular and Epigenetic Expressions as Novel Biomarkers in Critically Ill Polytrauma Patients with Acute Kidney Injury (AKI).

BACKGROUND: A high percentage of the critically ill polytrauma patients develop acute kidney injury (AKI) secondary to trauma and are therefore prone to high morbidity and mortality rates. One of the main objectives in these cases is the fast detection of the condition and continuous rigorous monitoring of the patients. Currently the panel of biomarkers available for monitoring and for the prognosis of AKI is limited. Numerous studies have proven the importance of microRNAs in this field. In this actualization paper we wish to summarize the most relevant microRNAs that can be used as biomarkers for patients with AKI. METHODS: For this paper, we looked into the studies available in scientific databases such as PubMed and Scopus. For the analysis we used the following key words: "miRNAs biomarker", "acute kidney injury AKI", "genetic expression in AKI", and "epigenetic microRNAs biomarkers in AKI". RESULTS: Numerous studies have shown high specificity for certain microRNA species in the case of patients with AKI. Moreover, they have reported a series of microRNAs that present high specificity and that have a strong expression in fluids that can be sampled through non-invasive methods, such as urine and saliva. CONCLUSIONS: The expression of microRNAs can be successfully used in the future as a non-invasive method for the evaluation and monitoring of AKI patients.

Circulating microRNAs Expressions as Genetic Biomarkers in Pancreatic Cancer Patients Continuous Non-Invasive Monitoring.

BACKGROUND: Pancreatic cancer is one of the most important causes of death worldwide. The main cause is late detection. Also, an important factor playing a role in altering the clinical status of these patients is the lack of methods for the evaluation of therapeutic response. A marker that can be useful, both in early diagnosis and in evaluating and monitoring non-invasive treatment response, is analyzing the expression of miRNAs. In this paper, we summarize genetic and epigenetic aspects of miRNAs in pancreatic cancer. Moreover, we want to emphasize potential miRNAs expressions that can be used as biomarkers for the management of patients with pancreatic cancer. METHODS: Studies available in scientific databases, such as PubMed and Scopus, were analyzed for conducting the present study. The keywords "miRNAs expression", "pancreatic cancer", and "genetic biomarkers" were used in the search engine. RESULTS: Following the searches, 187 primary scientific articles were analyzed. After rigorous analysis 40 articles were selected for the study. A high percentage of papers highlight the importance of using microRNAs as modern, non-invasive, and accurate biomarkers, designed for the early diagnosis and continuous monitoring of both the clinical outcome and treatment response of the patient. CONCLUSIONS: The expression of miRNAs can be successfully used for the evaluation and non-invasive monitoring of patients with pancreatic cancer.

miRNAs Expressions and Interaction with Biological Systems in Patients with Alzheimer`s Disease. Using miRNAs as a Diagnosis and Prognosis Biomarker.

BACKGROUND: A high percentage of patients develop Alzheimer`s disease (AD). The main signs are loss of memory and cognitive functions which have a significant impact on lifestyle. Numerous studies have been conducted to identify new biomarkers for early diagnosis of patients with AD. An ideal biomarker is represented by the expression of miRNAs. In this paper, we want to summarize expressions miRNAs in AD. We also want to present the pathophysiological and genetic interactions of miRNAs with protein systems in these patients. METHODS: For the study, we examined available studies in scientific databases, such as PubMed and Scopus. The studies were searched using the keywords "miRNAs expression", "Alzheimer`s disease", "genetic polymorphisms", and "genetic biomarkers". RESULTS: For the assessment and monitoring of patients with AD, the expression of miRNAs can be used successfully due to increased specificity and selectivity. Moreover, the expression of miRNAs can provide important answers regarding possible genetic interactions and genetic therapeutic regimens. CONCLUSIONS: For the evaluation and non-invasive monitoring of patients with Alzheimer`s disease the expression of miRNAs can be successfully used.

Advances in Biomarkers in Critical Ill Polytrauma Patients.

BACKGROUND: The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient. In this paper we wish to summarize the recent studies of biomarkers useful for the intensive care unit (ICU) physician. METHODS: For this study the available literature on specific databases such as PubMed and Scopus was thoroughly analyzed. Each article was carefully reviewed and useful information for this study extracted. The keywords used to select the relevant articles were "sepsis biomarker", "traumatic brain injury biomarker" "spinal cord injury biomarker", "inflammation biomarker", "microRNAs biomarker", "trauma biomarker", and "critically ill patients". RESULTS: For this study to be carried out 556 original type articles were analyzed, as well as case reports and reviews. For this review, 89 articles with relevant topics for the present paper were selected. The critically ill polytrauma patient, because of the clinical complexity the case presents with, needs a series of evaluations and specific monitoring. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients. CONCLUSIONS: The biomarkers existing today, with regard to the critically ill polytrauma patient, can bring a significant contribution to increasing the survival rate, by adapting the therapy according to their expressions. Nevertheless, the necessity remains to research new non-invasive diagnostic methods that present with higher specificity and selectivity.

Literature Research Regarding miRNAs' Expression in the Assessment and Evaluation of the Critically Ill Polytrauma Patient with Traumatic Brain and Spinal Cord Injury.

BACKGROUND: One of the most severe conditions specific to the critically ill polytrauma patient is traumatic brain injury and traumatic spinal cord injury. The mortality rate is high in the case of these patients, both because of the direct traumatic lesions, and because of the pathophysiological imbalances associated with trauma. Amongst the most common pathologies associated with the critically ill polytrauma patients responsible for a lower survival rate, are redox imbalance, systemic inflammatory response, infections, and multiple organ dysfunction syndrome. METHODS: For this study, was analysed the literature available on PubMed. The key words used in the search were "traumatic brain injury", "spinal cord injury", "microRNAs expression", "polytrauma patients", and "biomarkers". RESULTS: For the study were selected 34 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals, which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: A new era for biomarkers is represented by the expression of miRNAs. In the case of the critically ill polytrauma patient, using miRNAs' expression as biomarkers for the evaluation and monitoring of the molecular and pathophysiological dysfunctions can bring a range of valuable answers that could contribute to an increased survival rate.

The Use of Lipid Peroxidation Expression as a Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient.

BACKGROUND: The critically ill polytrauma patient, apart from the primary, traumatic injuries and the secondary, port-traumatic injuries, presents with a series of molecular disasters. Dysfunctions of the biochemical pathways and molecular damage add to the worsening of the clinical status of these patients, one of the most well-known molecular phenomena being oxidative stress (OS), responsible for an escalation of the inflammatory status, multiple infections, and multiple organ dysfunction syndrome (MODS). METHODS: For this study was analysed the literature available on PubMed and Scopus. The key words used in the search were "oxidative stress", "lipid peroxidation", "critically ill", "polytrauma patients", and "biomarkers oxidative stress". RESULTS: For the study we selected 47 science articles. The oxidative attack on lipids is responsible for the biosynthesis of an increased quantity of free radicals (FR), which further intensifies and aggravates the redox status in these patients. CONCLUSIONS: One of the most aggressive redox mechanisms related to lipid molecules is known as lipid peroxidation (LPOX).

Modulation of the Redox Expression and Inflammation Response in the Critically Ill Polytrauma Patient with Thoracic Injury. Statistical Correlations between Antioxidant Therapy.

BACKGROUND: One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables. METHODS: This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death. RESULTS: Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865). CONCLUSIONS: Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

Using Circulating miRNAs as Biomarkers for the Evaluation and Monitoring of the Mitochondrial Damage in the Critically Ill Polytrauma Patients.

BACKGROUND: The multiple-traumatic critical patient presents a variety of pathophysiological, cellular, and molecular dysfunctions. One of the most important is represented by mitochondrial damage which afterwards is responsible for the augmentation and worsening of a series of pathologies that lead to the worsening of the clinical status of the patient. The severe inflammatory response, sepsis, and the redox imbalance are other pathologies that together with the multiple traumas are responsible for the mitochondrial dysfunctions. As an overview, we can say that both the mitochondrial damage as well as the clinical statuses of those patients are responsible for an increase in the chances of multiple organ dysfunction syndrome and death of critical patients with multiple trauma from the Intensive Care Units (ICU). In this paper we wish to summarize the microRNAs that can be used as biomarkers for evaluation and monitoring of the mitochondrial activity in critical patients with multiple traumas. METHODS: For the paper, literature available in the international databases PubMed and Scopus until the year 2015 has been consulted. The key words used for the article search were "mitochondrial damage", "microRNAs biomarkers", and "critically ill polytrauma patients". RESULTS: As a result of the research based on the key words presented above, we found 234 papers. From those, after rigorous analysis 64 were selected as being in conformity with the needs of this paper. CONCLUSIONS: The critical polytrauma patient needs a specific evaluation and monitoring due to the complexity of the dysfunctions that appear at the cellular level. The use of microRNAs as biomarkers for the mitochondrial damage can be of real use for intensive care medicine. Nevertheless, more studies are required in order to determine a larger panel of microRNAs which can have an impact on mitochondrial damage.

Using the Expression of miRNAs as Biomarkers for the Evaluation Acute Respiratory Distress Syndrome in the Critically Ill Polytrauma Patient.

BACKGROUND: A high percentage of critically ill polytrauma patients develop acute respiratory distress syndrome (ARDS), both because of the primary traumatic injuries and because of the secondary post-traumatic injuries. For adequate management of these patients, new complex evaluation and monitoring methods are needed, methods that could answer as many questions as possible regarding the pathophysiological changes associated with ARDS. Currently, a series of clinical and biochemical markers are being used which unfortunately do not respond to the needs of an intensive care clinician. Therefore, the changes of miRNAs have been intensely researched in the case of patients with ARDS. Moreover, using them as biomarkers for ARDS brings a series of answers regarding the pathophysiological changes associated to ARDS, making them biomarkers of the future in laboratory medicine. METHODS: In order for this research study to be carried out the literature found on Scopus and PubMed on the topic was consulted, up to the year 2015. The key words used for the articles were "acute respiratory distress syndrome ARDS", "biomarkers for ARDS", "critically ill polytrauma patients", "miRNAs expression in ARDS", "miRNAs expression in sepsis", "miRNAs in critically ill patients" and "miRNAs biomarker". Research articles in English, German, and French were included in the search. RESULTS: Following the search using the above mentioned key words, 567 articles were found. After a rigorous analysis of these articles 55 of them were selected for our study. CONCLUSIONS: Using miRNAs for the evaluation and monitoring of ARDS makes them a biomarker of the future, because of the complex answers they bring to questions related both to the main injury caused by ARDS and to the associated pathophysiology.