Factors affecting adherence to recommendations on pre-operative cardiac testing: A cohort study.

BACKGROUND: Cardiac risk evaluation prior to noncardiac surgery is fundamental to tailor peri-operative management to patient's estimated risk. Data on the degree of adherence to guidelines in patients at cardiovascular risk in Europe and factors influencing adherence are underexplored. OBJECTIVES: The aim of this analysis was to describe the degree of adherence to [2014 European Society of Cardiology (ESC)/European Society of Anaesthesiology (ESA) guidelines] recommendations on rest echocardiography [transthoracic echocardiography (TTE)] and to stress imaging prior to noncardiac surgery in a large European sample and to assess factors potentially affecting adherence. DESIGN: Secondary analysis of a multicentre, international, prospective cohort study (MET-REPAIR). SETTING: Twenty-five European centres of all levels of care that enrolled patients between 2017 and 2020. PATIENTS: With elevated cardiovascular risk undergoing in-hospital elective, noncardiac surgery. MAIN OUTCOME MEASURES: (Non)adherence to each pre-operative TTE and stress imaging recommendations classified as guideline-adherent, overuse and underuse. We performed descriptive analysis. To explore the impact of patients' sex, age, geographical region, and hospital teaching status, we conducted multivariate multinominal regression analysis. RESULTS: Out of 15 983 patients, 15 529 were analysed (61% men, mean age 72 ±â€Š8 years). Overuse (conduction in spite of class III) and underuse (nonconduction in spite of class I recommendation) for pre-operative TTE amounted to 16.6% (2542/15 344) and 6.6% (1015/15 344), respectively. Stress imaging overuse and underuse amounted to 1.7% (241/14 202) and 0.4% (52/14 202) respectively. Male sex, some age categories and some geographical regions were significantly associated with TTE overuse. Male sex and some regions were also associated with TTE underuse. Age and regions were associated with overuse of stress imaging. Male sex, age, and some regions were associated with stress imaging underuse. CONCLUSION: Adherence to pre-operative stress imaging recommendation was high. In contrast, adherence to TTE recommendations was moderate. Both patients' and geographical factors affected adherence to joint ESC/ESA guidelines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03016936.

Intraoperative Oxygen Consumption and Postoperative Immune Response in Colorectal Oncological Surgery: A Prospective, Monocentric Pilot Study.

Surgical resection is the key treatment for colorectal cancer, but the extent of surgical trauma has been implied as a key factor for the oncologic outcome. The immune stress response to surgical trauma generates a cascade of immunological events implying neutrophils' perioperative change generating NETosis, N killer decrease, and platelets' activation that may influence postoperative surgical outcome, tumor cell growth, and future oncogenesis. The present study aimed to investigate the correlation between intraoperative oxygen consumption (VO2) and the dynamic variation of neutrophils, lymphocytes, and platelets in the perioperative period to identify an intraoperative tool that could predict the postoperative immune response. Twenty-six colorectal oncological surgical patients were enrolled in an observational, prospective, monocentric study, over 18 months. Serum neutrophils, lymphocytes, and thrombocytes values were collected in the preoperative period and on the third postoperative day, oxygen consumption was measured and recorded every 15 min during surgery using indirect calorimetry. We compared oxygen consumption measurements registered 30 min after induction of anesthesia (VO2a) and the first value registered after abdominal wall closure (VO2b) to perioperative variation of absolute neutrophils (VNC), lymphocytes (VLC), and platelets (VPC) count. Our results proved a significant correlation between VO2 variation and neutrophils' perioperative dynamic assessed by VNC (correlation coefficient = 0.547, p < 0.01, 95% confidence interval (CI) =0.175, 0.783). We also noticed a correlation between VPC and VO2 (correlation coefficient = -0.603, p < 0.01, 95% CI = -0.815, -0.248). No correlation could be shown between VO2 and VLC variation (p = 0.39). In conclusion, intraoperative VO2 variation measured by indirect calorimetry correlates well with perioperative neutrophils and platelets count dynamic variations and can be used as an early prognosis marker of postoperative immune response and surgical outcome in colorectal oncological surgery.

The Surgical Stress Response and Anesthesia: A Narrative Review.

The human physiological response "to stress" includes all metabolic and hormonal changes produced by a traumatic event at the micro or macro cellular levels. The main goal of the body's first response to trauma is to keep physiological homeostasis. The perioperative non-specific adaptation response can sometimes be detrimental and can produce systemic inflammatory response syndrome (SIRS), characterized by hypermetabolism and hyper catabolism. We performed a narrative review consisting of a description of the surgical stress response's categories of changes (neurohormonal and immunological response) followed by reviewing methods found in published studies to modulate the surgical stress response perioperatively. We described various preoperative measures cited in the literature as lowering the burden of surgical trauma. This article revises the anesthetic drugs and techniques that have an impact on the surgical stress response and proven immune-modulatory effects. We also tried to name present knowledge gaps requiring future research. Our review concludes that proper preoperative measures, adequate general anesthetics, multimodal analgesia, early postoperative mobilization, and early enteral nutrition can decrease the stress response to surgery and ease patient recovery. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system and inflammatory system, with a consecutive impact on cancer recurrence and long-term outcomes.

Energy Expenditure, a New Tool for Monitoring Surgical Stress in Colorectal Oncological Patients: A Prospective, Monocentric Study.

BACKGROUND: Surgical stress response in colorectal surgery consists of a neurohormonal and an immunological response and influences oncological outcomes. The intensity of surgical trauma influences mortality, morbidity, and metastasis' occurrence in colorectal neoplasia. Energy expenditure (EE) stands for the body's energy consumed to keep its homeostasis and can be either calculated or measured by direct or indirect calorimetry. AIM: The present study attempted to evaluate surgical stress response using EE measurement and compare it to the postoperative cortisol dynamic. METHODS: A prospective, monocentric study was conducted over a period of one year in the Anesthesiology Department including 21 patients from whom serum cortisol values were collected in the preoperative period and on the first postoperative day, and EE was measured and recorded every 15 minutes throughout surgery using the indirect calorimetry method. The study compared EE values' dynamic registered 30 minutes after intubation and 30 minutes before extubating (after abdominal closure) to cortisol perioperative dynamic. RESULTS: We enrolled 21 patients and 84 measurements were recorded, 42 probes of serum cortisol and 42 measurements of EE. The mean value of the first measurement of serum cortisol was 13.60±3.6 µg and the second was 16.21±6.52 µg. The average value of the first EE recording was 1273.9±278 kcal and 1463.4±398.2 kcal of the second recording. The bivariate analysis performed showed a good correlation between cortisol variation and EE's variation (Spearman coefficient=0.666, p<0.001, CI=0.285, 0.865). In nine cases (42.85%), cortisol value at 24 hours reached the baseline or below the baselines preoperative value. In eight cases (38.09%), patients' EE at the end of the surgery was lower than that recorded at the beginning of the surgery. CONCLUSIONS: Intraoperative EE variation correlated well with cortisol perioperative dynamic and stood out in this study as a valuable and accessible predictor of surgical stress in colorectal surgery.

Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Pain in Colorectal Surgery: How Does It Occur and What Tools Do We Have for Treatment?

Pain is a complex entity with deleterious effects on the entire organism. Poorly controlled postoperative pain impacts the patient outcome, being associated with increased morbidity, inadequate quality of life and functional recovery. In the current surgical environment with less invasive surgical procedures increasingly being used and a trend towards rapid discharge home after surgery, we need to continuously re-evaluate analgesic strategies. We have performed a narrative review consisting of a description of the acute surgical pain anatomic pathways and the connection between pain and the surgical stress response followed by reviewing methods of multimodal analgesia in colorectal surgery found in recent literature data. We have described various regional analgesia techniques and drugs effective in pain treatment, emphasizing their advantages and concerns. We have also tried to identify present knowledge gaps requiring future research. Our review concludes that surgical pain has peculiarities that make its management complex, implying a consistent, multimodal approach aiming to block both peripheral and central pain pathways.

Postoperative Staphylococcus aureus Infections in Patients With and Without Preoperative Colonization.

Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors. Design, Setting, and Participants: This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio. Exposure: Preoperative S aureus colonization. Main Outcomes and Measures: The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models. Results: In total, 5004 patients (median [IQR] age, 66 [56-72] years; 2510 [50.2%] female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio [AHR], 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs. Conclusions and Relevance: In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

Hematological Parameters and Procalcitonin as Discriminants between Bacterial Pneumonia-Induced Sepsis and Viral Sepsis Secondary to COVID-19: A Retrospective Single-Center Analysis.

Bacterial and viral sepsis induce alterations of all hematological parameters and procalcitonin is used as a biomarker of infection and disease severity. Our aim was to study the hematological patterns associated with pulmonary sepsis triggered by bacteria and Severe Acute Respiratory Syndrome-Coronavirus-type-2 (SARS-CoV-2) and to identify the discriminants between them. We performed a retrospective, observational study including 124 patients with bacterial sepsis and 138 patients with viral sepsis. Discriminative ability of hematological parameters and procalcitonin between sepsis types was tested using receiver operating characteristic (ROC) analysis. Sensitivity (Sn%), specificity (Sp%), positive and negative likelihood ratios were calculated for the identified cut-off values. Patients with bacterial sepsis were older than patients with viral sepsis (p < 0.001), with no differences regarding gender. Subsequently to ROC analysis, procalcitonin had excellent discriminative ability for bacterial sepsis diagnosis with an area under the curve (AUC) of 0.92 (cut-off value of >1.49 ng/mL; Sn = 76.6%, Sp = 94.2%), followed by RDW% with an AUC = 0.87 (cut-off value >14.8%; Sn = 80.7%, Sp = 85.5%). Leukocytes, monocytes and neutrophils had good discriminative ability with AUCs between 0.76-0.78 (p < 0.001), while other hematological parameters had fair or no discriminative ability. Lastly, procalcitonin value was strongly correlated with disease severity in both types of sepsis (p < 0.001). Procalcitonin and RDW% had the best discriminative ability between bacterial and viral sepsis, followed by leukocytes, monocytes and neutrophils. Procalcitonin is a marker of disease severity regardless of sepsis type.

Veno-venous extracorporeal membrane oxygenation, cytokine removal and continuous renal replacement therapy in a severe burn adult patient.

Acute respiratory distress syndrome (ARDS) can develop early in burn patients with inhalation injury in the presence of cytokine storm and the proinflammatory response can be a supplemental factor for ARDS aggravation. We report the case of a 41-years old male with 25% total body surface area deep partial thickness burns to upper body extremity and grade II inhalational injury who developed severe ARDS, nosocomial pneumonia, and septic shock. Veno-venous extracorporeal membrane oxygenation (VV ECMO) and continuous renal replacement therapy (CRRT) with hemoadsorption were successfully used at different moments to overcome critical situations. Although debatable, the use of ECMO in burn patients with severe ARDS could be considered when conventional treatment fails. The use of CRRT combined with hemoadsorption may limit the proinflammatory response sustained by the combination between major burn, ECMO and sepsis.

Development and Internal Validation of a New Prognostic Model Powered to Predict 28-Day All-Cause Mortality in ICU COVID-19 Patients-The COVID-SOFA Score.

Background: The sequential organ failure assessment (SOFA) score has poor discriminative ability for death in severely or critically ill patients with Coronavirus disease 2019 (COVID-19) requiring intensive care unit (ICU) admission. Our aim was to create a new score powered to predict 28-day mortality. Methods: Retrospective, observational, bicentric cohort study including 425 patients with COVID-19 pneumonia, acute respiratory failure and SOFA score ≥ 2 requiring ICU admission for ≥72 h. Factors with independent predictive value for 28-day mortality were identified after stepwise Cox proportional hazards (PH) regression. Based on the regression coefficients, an equation was computed representing the COVID-SOFA score. Discriminative ability was tested using receiver operating characteristic (ROC) analysis, concordance statistics and precision-recall curves. This score was internally validated. Results: Median (Q1−Q3) age for the whole sample was 64 [55−72], with 290 (68.2%) of patients being male. The 28-day mortality was 54.58%. After stepwise Cox PH regression, age, neutrophil-to-lymphocyte ratio (NLR) and SOFA score remained in the final model. The following equation was computed: COVID-SOFA score = 10 × [0.037 × Age + 0.347 × ln(NLR) + 0.16 × SOFA]. Harrell's C-index for the COVID-SOFA score was higher than the SOFA score alone for 28-day mortality (0.697 [95% CI; 0.662−0.731] versus 0.639 [95% CI: 0.605−0.672]). Subsequently, the prediction error rate was improved up to 16.06%. Area under the ROC (AUROC) was significantly higher for the COVID-SOFA score compared with the SOFA score for 28-day mortality: 0.796 [95% CI: 0.755−0.833] versus 0.699 [95% CI: 0.653−0.742, p < 0.001]. Better predictive value was observed with repeated measurement at 48 h after ICU admission. Conclusions: The COVID-SOFA score is better than the SOFA score alone for 28-day mortality prediction. Improvement in predictive value seen with measurements at 48 h after ICU admission suggests that the COVID-SOFA score can be used in a repetitive manner. External validation is required to support these results.

The Impact of General Anesthesia on Redox Stability and Epigenetic Inflammation Pathways: Crosstalk on Perioperative Antioxidant Therapy.

Worldwide, the prevalence of surgery under general anesthesia has significantly increased, both because of modern anesthetic and pain-control techniques and because of better diagnosis and the increased complexity of surgical techniques. Apart from developing new concepts in the surgical field, researchers and clinicians are now working on minimizing the impact of surgical trauma and offering minimal invasive procedures due to the recent discoveries in the field of cellular and molecular mechanisms that have revealed a systemic inflammatory and pro-oxidative impact not only in the perioperative period but also in the long term, contributing to more difficult recovery, increased morbidity and mortality, and a negative financial impact. Detailed molecular and cellular analysis has shown an overproduction of inflammatory and pro-oxidative species, responsible for augmenting the systemic inflammatory status and making postoperative recovery more difficult. Moreover, there are a series of changes in certain epigenetic structures, the most important being the microRNAs. This review describes the most important molecular and cellular mechanisms that impact the surgical patient undergoing general anesthesia, and it presents a series of antioxidant therapies that can reduce systemic inflammation.

Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort.

BACKGROUND: During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality. METHODS: We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021. RESULTS: We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients. CONCLUSION: In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.

Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients.

BACKGROUND: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). OBJECTIVES: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. METHODS: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. RESULTS: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06-8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21-5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7-4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31-3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2-2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13-2.49, p = 0.01). CONCLUSIONS: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

Neuromuscular monitoring: an update.

This review makes an advocacy for neuromuscular blockade monitoring during anaesthesia care, by: (i) describing the fundamental principles of the methods currently available, at the same time emphasizing quantitative recording measurements; (ii) describing the different ways in which muscles respond to the effect of neuromuscular blockade and their use in clinical practice; (iii) presenting results of different studies on timing and agents of neuromuscular block reversal, including a recommendation for sugammadex use and experimental results with calabadion and (iv) in the end emphasizing the need for implementing neuromuscular monitoring as a practice that should be used every time a neuromuscular block is required.

Perioperative Patient Blood Management Programme. Multidisciplinary recommendations from the Patient Blood Management Initiative Group.

Patients with untreated anaemia or iron deficiency who undergo surgical procedures have an increased risk for mortality and morbidity. Patient Blood Management programmes address this issue worldwide and try to improve patient outcomes through a complex set of measures targeting anaemia correction, minimisation of bleeding and improvement of anaemia tolerance, in all phases of perioperative care. The Patient Blood Management Initiative Group is a multidisciplinary team of physicians from specialties including anaesthesiology, nephrology, surgery, orthopaedics, haematology, gastroenterology and transfusion medicine. The team has elaborated ten recommendations, divided into five categories, in order to implement a Patient Blood Management programme in Romania, using the most recent and relevant evidence. The document was discussed during three meetings which took place during October 2016 and May 2017 and the result was modified and updated via e-mail.

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.