The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Prediction of In-Hospital Outcomes in Patients with Traumatic Brain Injury Using Computed Tomographic Scoring Systems: A Comparison Between Marshall, Rotterdam, and Neuroimaging Radiological Interpretation Systems.

OBJECTIVE: This study aimed to compare the prognostic value of Marshall, Rotterdam, and Neuroimaging Radiological Interpretation Systems (NIRIS) in predicting the in-hospital outcomes of patients with traumatic brain injury. METHODS: We identified 250 patients with traumatic brain injury in a retrospective single-center cohort from 2019 to 2020. Computed tomography (CT) scans were reviewed by two radiologists and scored according to three CT scoring systems. One-month outcomes were evaluated, including hospitalization, intensive care unit admission, neurosurgical procedure, and mortality. Logistic regression analysis was performed to identify scoring systems and outcome relationships. The best cutoff value was calculated using the receiver operating characteristic curve model. RESULTS: Eighteen patients (7.2%) died in the 1-month follow-up. The mean age and Glasgow Coma Scale of survivors differed significantly from nonsurvivors. Subarachnoid hemorrhage and compressed/absent cisterns were dead patients' most frequent CT findings. All three scoring systems had good discrimination power in mortality prediction (area under the receiver operating characteristic curve of the Marshall, Rotterdam, and NIRIS was 0.78, 0.86, and 0.84, respectively). Regarding outcome, three systems directly correlated with unfavorable outcome prediction. CONCLUSIONS: The Marshall, Rotterdam, and NIRIS are good predictive models for mortality and outcome prediction, with slight superiority of the Rotterdam in mortality prediction and the Marshall in intensive care unit admission and neurosurgical procedures.

Implementation of an algorithm for chest imaging in blunt trauma decreases use of CT-scan: Resource management in a middle-income country.

PURPOSE: Due to the low sensitivity of chest radiography, chest CT-scan is usually recommended for the evaluation of high-risk blunt trauma patients. Considering the radiation exposure and costs accompanying routine CT-scan, the aim of this study was to design and implement an evidence-based institutional algorithm for selective chest imaging in high energy blunt trauma patients and evaluate its effect on patient outcome and resource utilization. METHODS: For this field trial, an institutional evidence-based algorithm for chest trauma imaging was designed according to existing data and expert panel. After final consent and ethic committee approval, the algorithm was integrated in the diagnostic flow sheet in the emergency department and patient data were collected from the pre- and post-implementation period. RESULTS: One-hundred and sixty-five patients before algorithm implementation and 158 patients after that were included. Chest CT-scan was requested for 93% of patients in the pre-implementation group and for 73% in the post-implementation group (P<0.001). Length of stay in hospital was slightly shorter in the post-implementation group (p = 0.036), however, duration of stay in emergency room and ICU, pulmonary complications and mortality showed no significant difference. CONCLUSION: Implementation of an algorithm for limiting chest CT-scan to a subgroup of patients with a higher risk of chest injuries can reduce radiation exposure and more useful distribution of resources without harming the patients. Each institution should use institutional guidelines and algorithms with respect to patient load, available resources and desired sensitivity for injury detection.

Metabolic Response to Omega-3 Fatty Acids and Vitamin E Co-Supplementation in Patients with Fibrocystic Breast Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: There is scarce data on the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic status in patients with fibrocystic breast disease (FBD). The current study was carried out to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on metabolic status in patients with FBD. METHODS: A randomized clinical trial was conducted on 56 patients with FBD. Participants were randomly divided into two groups to receive either 1000 mg omega-3 fatty acids plus 400 mg vitamin E (n = 28) or placebo (n = 28) for 12 weeks. Fasting blood samples were taken at the beginning of the study and after 12 weeks of intervention to determine inflammatory factors, biomarkers of oxidative stress, and metabolic profiles. RESULTS: After 12 weeks of intervention, changes in serum high-sensitivity C-reactive protein (-2171.4 ± 3189.1 vs. +696.9 ± 2774.8 ng/mL, P = 0.001) and plasma nitric oxide (+1.8 ± 4.0 vs. -0.1 ± 2.4 µmol/L, P = 0.04) in supplemented women were significantly different from those in the placebo group. In addition, compared to the placebo group, subjects who consumed omega-3 fatty acids plus vitamin E supplements had significantly decreased serum insulin concentrations (-3.2 ± 6.5 vs. -0.2 ± 1.7 µIU/mL, P = 0.01), the homeostasis model of assessment-estimated insulin resistance (-0.8 ± 1.7 vs. -0.02 ± 0.4, P = 0.03), serum triglycerides levels (-11.5 ± 47.3 vs. +10.6 ± 24.3 mg/dL, P = 0.03) and VLDL-cholesterol (-2.3 ± 9.5 vs. +2.1 ± 4.9 mg/dL, P = 0.03), as well as increased quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. +0.001 ± 0.007, P = 0.001) and HDL-cholesterol (+3.4 ± 6.0 vs. -1.3 ± 4.3 mg/dL, P = 0.001). CONCLUSION: Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks had beneficial effects on inflammatory markers and metabolic profiles in patients with FBD.

Correlation Between Intra-Abdominal Free Fluid and Solid Organ Injury in Blunt Abdominal Trauma.

BACKGROUND: In previous studies, the diagnostic value of Focused Assessment with Sonography for Trauma (FAST) has been evaluated but few studies have been performed on the relationship between the amount of free intra-abdominal fluid and organ injury in blunt abdominal trauma. To select patients with a higher probability of intra-abdominal injuries, several scoring systems have been proposed based on the results of FAST. OBJECTIVES: The aim of this study was to determine the prognostic value of FAST according to the Huang scoring system and to propose a cut-off point for predicting the presence of intra-abdominal injuries on the Computed Tomography (CT) scan. The correlation between age and Glasgow Coma Scale (GCS) and the presence of intra-abdominal injuries on the CT scan was also assessed. PATIENTS AND METHODS: This study was performed on 200 patients with severe blunt abdominal trauma who had stable vital signs. For all patients, FAST-ultrasound was performed by a radiologist and the free fluid score in the abdomen was calculated according to the Huang score. Immediately, an intravenous contrast-enhanced abdominal CT scan was performed in all patients and abdominal solid organ injuries were assessed. Results were analyzed using Kruskal-Wallis test, Mann-Whitney test and ROC curves. The correlation between age and GCS and the presence of intra-abdominal injuries on CT-scan was also evaluated. RESULTS: The mean age of the patients was 29.6 ± 18.3 years and FAST was positive in 67% of the subjects. A significant correlation was seen between the FAST score and the presence of organ injury on CT scan (P < 0.001). Considering the cut-off point of 3 for the free fluid score (with a range of 0-8), sensitivity, specificity, positive predictive value and negative predictive value were calculated to be 0.83, 0.98, 0.93, and 0.95, respectively. Age and GCS showed no significant correlation with intra-abdominal injuries. CONCLUSIONS: It seems that FAST examination for intra-abdominal fluid in blunt trauma patients can predict intra-abdominal injuries with very high sensitivity and specificity. Using the scoring system can more accurately determine the probability of the presence of abdominal injuries with a cut-off point of three.

Routine Chest Computed Tomography and Patient Outcome in Blunt Trauma.

BACKGROUND: Computerized Tomography (CT) scan is gaining more importance in the initial evaluation of patients with multiple trauma, but its effect on the outcome is still unclear. Until now, no prospective randomized trial has been performed to define the role of routine chest CT in patients with blunt trauma. OBJECTIVES: In view of the considerable radiation exposure and the high costs of CT scan, the aim of this study was to assess the effects of performing the routine chest CT on the outcome as well as complications in patients with blunt trauma. PATIENTS AND METHODS: After approval by the ethics board committee, 100 hemodynamically stable patients with high-energy blunt trauma were randomly divided into two groups. For group one (control group), only chest X-ray was requested and further diagnostic work-up was performed by the decision of the trauma team. For group two, a chest X-ray was ordered followed by a chest CT, even if the chest X-ray was normal. Injury severity, total hospitalization time, Intensive Care Unit (ICU) admission time, duration of mechanical ventilation and complications were recorded. Data were evaluated using t-test, Man-Whitney and chi-squared test. RESULTS: No significant differences were found regarding the demographic data such as age, injury severity and Glasgow Coma Scale (GCS). Thirty-eight percent additional findings were seen in chest CT in 26% of the patients of the group undergoing routine chest CT, leading to 8% change in management. The mean of in-hospital stay showed no significant difference in both groups with a P value of 0.098. In addition, the mean ICU stay and ventilation time revealed no significant differences (P values = 0.102 and 0.576, respectively). Mortality rate and complications were similar in both groups. CONCLUSIONS: Performing the routine chest CT in high-energy blunt trauma patients (with a mean injury severity of 9), although leading to the diagnosis of some occult injuries, has no impact on the outcome and does not decrease the in-hospital stay and ICU admission time. It seems that performing the routine chest CT in these patients may lead to overtreatment of nonsignificant injuries. The decision about performing routine CT scan in a trauma center should be made cautiously, considering the detriments and benefits.