Early Prognostic Marker Research Articles

Role of the neutrophil/lymphocyte ratio in patients with metastatic castration-resistant prostate cancer treated first-line with abiraterone

IntroductionIn patients with prostate cancer, high NLR seems to be associated with worse survival. Abiraterone acetate (AA) is a new generation hormonal treatment that has shown to increase PFS and OS in mCRPC. Material and methodsRetrospective analysis of patients treated with AA in our center (December 2012-September 2018). We analyzed the association of the NLR (<o≥3) before and after 6 months of treatment with PSA response, PFS, OS, and hormone sensitivity prior to AA (<or> 12 months). ResultsWe have treated 56 patients with a median age of 82 (62–94), of which 22 (39%) had NLR ≥ 3 before treatment.There is a statistically significant association between the NLR prior to treatment <3 and PSA response, OR = 9444, p = 0.001, and there was no association with the NLR at 6 months of treatment.Statistically significant differences were found between the groups of NLR < and> 3 prior to treatment with abiraterone in PFS with 15 months of median vs 9 and p = 0.008, and in OS with 20 months vs 9 with p = 0.014.With respect to the determination of NLR at 6 months, there are no differences in the survival curves between both groups.There are significant differences between the NLR prior to treatment according to the length of hormone sensitivity (p = 0.026). ConclusionsOur results suggest that NLR could provide relevant information and could act as an early and accessible prognostic marker in patients with mCRPC in first line treatment with Abiraterone.

Papel del índice neutrófilo/linfocito en pacientes con cáncer de próstata resistente a castración metastásicos tratados en primera línea con abiraterona

IntroductionIn patients with prostate cancer, high NLR seems to be associated with worse survival. Abiraterone acetate (AA) is a new generation hormonal treatment that has shown to increase PFS and OS in mCRPC. Material and methodsRetrospective analysis of patients treated with AA in our center (December 2012-September 2018). We analyzed the association of the NLR (< or ≥ 3) before and after 6 months of treatment with PSA response, PFS, OS, and hormone sensitivity prior to AA (< or> 12 months). ResultsWe have treated 56 patients with a median age of 82 (62-94), of which 22 (39%) had NLR ≥ 3 before treatment.There is a statistically significant association between the NLR prior to treatment<3 and PSA response, OR=9,444, P=.001, and there was no association with the NLR at 6 months of treatment.Statistically significant differences were found between the groups of NLR<and> 3 prior to treatment with abiraterone in PFS with 15 months of median vs. 9 and P=.008, and in OS with 20 months vs. 9 with P=.014.With respect to the determination of NLR at 6 months, there are no differences in the survival curves between both groups.There are significant differences between the NLR prior to treatment according to the length of hormone sensitivity (P=.026). ConclusionsOur results suggest that NLR could provide relevant information and could act as an early and accessible prognostic marker in patients with mCRPC in first line treatment with Abiraterone.

English

English

An investigation of the use of SCUBE1 protein as an early prognostic marker in predicting prognosis after cardiopulmonary resuscitation in cardiac arrest patients

Aim: To evaluate the usefulness of Signal Peptide-CUB-EGF Domain-Containing Protein-1 (SCUBE1) protein as an early prognostic marker in predicting survival, resuscitation success, and good neurological outcome following cardiopulmonary resuscitation (CPR) in cardiac arrest patients.Material and Methods: Non-traumatic cardiac arrest patients presenting to the emergency department over a six-month period were included in the study. Blood specimens were collected for SCUBE1 measurement at the start of CPR. SCUBE1 levels investigated at the start of CPR were compared, and their usefulness in predicting patients with long-term survival and exhibiting good neurological prognosis was evaluated.Results: The study group consisted of 65 non-traumatic cardiac arrest patients. Sustained return of spontaneous circulation (ROSC) was achieved in 26 (40%) of these 65 patients, and five (7.7%) cases concluded with good neurological prognosis after three months. Comparison of the patient groups with and without sustained ROSC in terms of SCUBE1 levels investigated at the start of CPR revealed no statistically significant difference between them (p=0.462). However, comparison of the patient groups with good and poor neurological prognosis in terms of SCUBE1 levels at the start of CPR revealed that SCUBE1 levels were twice as high in the poor neurological prognosis group as in the good neurological prognosis group, although the difference was not statistically significant.Conclusion: SCUBE1 levels measured at the start of CPR are not sufficient for predicting post-CPR survival and good neurological outcome.

The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort

BackgroundSince the Sepsis-3 criteria, change in Sequential Organ Failure Assessment (SOFA) score has become a key component of sepsis identification. Thus, it could be argued that reversal of this change (ΔSOFA) may reflect sepsis response and could be used as measure of efficacy in interventional trials. We aimed to assess the predictive performance of ΔSOFA for 28-day mortality.MethodsData from two previously published randomized controlled trials were studied: the first reporting on patients with severe Gram-negative infections as a derivation cohort and the second reporting on patients with ventilator-associated pneumonia as a validation cohort. Only patients with sepsis according to the Sepsis-3 definition were included in this analysis. SOFA scores were calculated on days 1, 2, 3, 5, 7, 14, and 28.ResultsWe included 448 patients within the derivation cohort and 199 within the validation cohort. Mean SOFA scores on day 1 were 6.06 ± 4.07 and 7.84 ± 3.39, and 28 day mortality 22.8% and 29.6%, respectively. In the derivation cohort, the earliest time point where ΔSOFA score predicted mortality was day 7 (AUROC (95% CI) 0.84 (0.80–0.89); p < 0.001). The best tradeoff for prediction was found with 25% changes (78% sensitivity, 80% specificity); less than 25% decrease of admission SOFA was associated with increased mortality (odds ratio for death 14.87). This finding was confirmed in the validation cohort.ConclusionsΔSOFA on day 7 is a useful early prognostic marker of 28-day mortality and could serve as an endpoint in future sepsis trials alongside mortality.Trial registrationClinicalTrials.gov numbers NCT01223690 and NCT00297674

Expression of MUC4 in Oral Dysplastic Epithelium

Background: Though various biological markers are available for improving the diagnostic accuracy early detection of disease progression remains a challenging task mainly due to lack of adequate early prognostic marker. Aim and Objectives: To evaluate the immunohistochemical expression of MUC4 in oral epithelial dysplasia and to compare the immuno histochemical expression of MUC4 in Oral Epithelia Dysplasia (OED) and its expression in the normal tissue specimens. Materials and Methods: The present retrospective study was undertaken to compare and evaluate the expression of MUC4 in oral epithelial dysplasia and normal. The study comprised of 45 cases of oral epithelial dysplasia and 10 controls. Control specimens were obtained from healthy oral mucosa of individuals undergoing oral surgery for disimpaction of third molars and orthodontic extractions. Serial sections of 3-4 microns thickness were made from the tissue blocks and were stained using immunohistochemical marker MUC4, using an immunoperoxidase technique (ABC method). The semi quantitative analysis of the stained sections was done by light microscopy according to the Immunoreactive Score (IRS) by Remmele and Stegner which evaluated percentage of positive cells and the staining intensity. Results: Less than 10% of positive cells were seen in 9 cases of mild dysplasia out of 15 cases and 3 cases showed 10 to 50% of positive cells. Whereas less than 10% of positive cells were seen in 6 cases of moderate dysplasia out of 15 cases and other 9 cases showed 16% and 42% of positive cells respectively. However, in severe dysplasia positive cells percentage increased to 10 to 50% in 10 cases and other cases showed less than 10% respectively. Conclusion: In the OED group a gradual increase in the staining pattern was observed from mild to moderate to severe dysplasia. Severe dysplasia cases exhibited the staining of entire thickness of epithelium. Thus, it may be concluded that MUC4 plays a very important role and can be reckoned as a handy tool or marker for diagnosis of OED.

The role of C-reactive protein after surgery for obesity and metabolic disorders.

C-reactive protein (CRP) rise might be different in patients with obesity due to chronic inflammation. The aim was to analyze postoperative CRP rise and its role as an early prognostic marker of infectious complications. Center of maximum care in Germany. Patients who underwent laparoscopic sleeve gastrectomy, laparoscopic Roux-en-Y gastric bypass, or laparoscopic one-anastomosis gastric bypass as primary treatment for severe obesity were included. Serum CRP and leukocyte count were measured preoperatively, on postoperative days (POD) 1 and 4 and were analyzed regarding sex, body mass index, waist circumference, obesity-associated diseases, laboratory measurements (glycosylated hemoglobin, triglycerides, cholesterol), surgical procedure, infectious complications, and infectious with anastomotic leakage. Four hundred seventy-one patients underwent surgery. Postoperative CRP rise was similar across sexes but lower in the super-super obese group (P < .05) and higher in the gastric bypass groups (P < .05). Linear regression model showed, that the higher preoperative value of waist circumference, the higher the preoperative CRP (beta value: .159, P = .006) and the lower the postoperative CRP rise on POD1 (beta value: -.171, P = .004) and 4 (beta value: -.170, P = .003). Only in the laparoscopic one-anastomosis gastric bypass group did a higher glycosylated hemoglobin predict a higher postoperative CRP rise (POD1: beta value: .434, P = .012; POD4: beta value: .513, P = .006). Fourteen patients (3%) developed infections, 7 of whom (1.5%) had anastomotic leakage. Leukocyte count was no predictor of infectious complications. The cut-off for CRP was 80.5 mg/L (POD1) and 164 mg/L (POD4), with 57.1% and 85.7% sensitivity and 97.9% and 99.6% specificity for anastomotic leakage. Standard postoperative CRP rises less in patients with higher waist circumference and super-super obesity, but more after gastric bypass procedures. CRP but not leukocyte count predicts early anastomotic healing after obesity surgery. These findings should be considered when interpreting CRP values in the routine clinical setting.

1719P - Fusion of immortalized myoblasts induces genomic instability that drives tumour development and progression

BackgroundSarcoma are a heterogeneous group of tumor which can be split into two subgroups with distinct genetics. Half of sarcoma presents an important genomic reorganization correlated to tumor aggressiveness. At this stage, the origin of this instability is still unknown. Cell fusion is a physiological mechanism involved in several processes including myoblast differentiation and already described to be involved in aneuploidy generation and genomic instability. We thus hypothesized that cell fusion could participate to sarcoma oncogenesis by generating genomic instability. MethodsWe established cell line of hybrids from spontaneous fusion of immortalized myoblasts. Tumor and metastasis development were evaluated upon grafting and whole genome and transcriptome sequencing with in-vitro mechanistic studies were performed to decipher phenotypes acquired by hybrids upon fusion. ResultsIn vitro hybrid cell lines show a more aggressive phenotype than parental cell lines by increasing proliferation and clonogenic capacities. Only hybrids form tumors upon grafting and may develop also metastasis. Aneuploidy triggered by cell fusion induces genome reorganization and in vivo tumor genome show alterations corresponding to those observed in human rhabdomyosarcoma. Indeed, 85% of hybrid tumors harbor DMD deletions as observed in sarcoma with myogenic origin. The study of this protein reveals that tumors lose the expression of Dp427 isoform which is the one reported as a tumor suppressor. This malignant transformation of hybrids is associated to transcriptomic remodeling toward a decrease of the expression of genes involved in muscle differentiation. ConclusionsTo our knowledge, this is the first model able to reproduce the complex genomic of sarcoma. The detection of those hybrid cells in sarcoma tumor allowed us to push forward they are involved in sarcoma development and progression and their quantification in tumors or in circulating cells could thus establish an early prognostic marker. Finally, specific therapeutic targeting of this hybrids could represent new approach. Legal entity responsible for the studyFrederic Chibon. FundingAssociation pour la Recherche contre le Cancer (ARC) Fondation pour la Recherche Médicale (FRM). DisclosureAll authors have declared no conflicts of interest.

Platelet-lymphocyte Ratio After Granulocyte Colony Stimulating Factor Administration: an Early Prognostic Marker in Septic Shock Patients With Chemotherapy-Induced Febrile Neutropenia.

Chemotherapy-induced febrile neutropenia (FN) causes life-threatening complications, but little is known in septic shock patients with FN. The aim of this study was to investigate the prognostic value of inflammatory markers, including C-reactive protein level, immature granulocyte count, white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), in septic shock patients with FN at admission and after granulocyte colony-stimulating factor (G-CSF) administration. Data on consecutive adult septic shock patients with FN treated with G-CSF between June 2012 and June 2017 were extracted from a prospectively compiled septic shock registry. Clinical and serial laboratory data at admission and <24 h after G-CSF administration were compared between nonsurvivor and 1-month survivor groups. Of 1,671 septic shock patients, 158 FN patients were treated with G-CSF and 114 (72.2%) survived for 1 month. At admission, no clinical and serial laboratory data were significant to predict survival. After G-CSF administration, PLR and APACHE II were independent predictors for 1-month survival. PLR after administration of G-CSF >100 (adjusted odds ratio [aOR], 9.394; 95% CI, 2.821-31.285, P < 0.001) showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.4%, 46.2%, 82.9%, and 60.0%, respectively, and APACHE II <28 (aOR, 6.944; 95% CI, 2.351-20.511, P < 0.001) showed sensitivity, specificity, PPV, and NPV of 86.8%, 63.6%, 86.1%, and 65.1%, respectively. After G-CSF administration in septic shock patients with chemotherapy-induced FN, PLR may be used as an early prognostic marker for mortality.

Thrombomodulin-expressing monocytes are associated with low-risk features in myelodysplastic syndromes and dampen excessive immune activation.

The bone marrow of patients with low-risk myelodysplastic syndromes (MDS) is often an inflammatory environment and associated with an active cellular immune response. An active immune response generally contributes to antitumor responses and may prevent disease progression. However, chronic immune stimulation can also induce cell stress, DNA damage and contribute to the pathogenesis of MDS. The protective mechanisms against excessive immune activation are therefore an important aspect of the pathophysiology of MDS and characterizing them may help us to better understand the fine balance between protective and destabilizing inflammation in lower-risk disease. In this study we investigated the role of thrombomodulin (CD141/BDCA-3) expression, a molecule with anti-inflammatory properties, on monocytes in the bone marrow and peripheral blood of MDS patients in different risk groups. Patient-derived classical monocytes showed high expression levels of thrombomodulin, whereas monocytes from healthy donors hardly expressed any thrombomodulin. The presence of thrombomodulin on monocytes from MDS patients correlated with lower-risk disease groups and better overall and leukemia-free survival. Using multidimensional mass cytometry, in an in-vitro setting, we showed that thrombomodulin-positive monocytes could polarize naïve T cells toward cell clusters which are closer to T helper type 2 and T regulatory cell phenotypes and less likely to contribute to effective immune surveillance. In conclusion, the expression of thrombomodulin on classical monocytes is a favorable and early prognostic marker in patients with low-risk MDS and may represent a new mechanism in the protection against disproportionate immune activation.

P03 Heme oxygenase 1 – a potential early prognostic marker for neurological outcome after aneurysmal subarachnoid hemorrhage

P03 Heme oxygenase 1 – a potential early prognostic marker for neurological outcome after aneurysmal subarachnoid hemorrhage

Predictive molecular tumor response through circulating DNA (cDNA) measurements and correlation with established prognostic markers in a series of solid tumors treated with multitargeted epigenetic therapy (MTET).

e13015 Background: Epigenetic dysregulation of certain genes contribute to the progression of cancers. Plasma ctDNA concentrations can reflect these altered genes and have been shown to correlate well with tumor burden. Methods: We planned to assess the correlation value of c DNA on known factors for prediction of overall survival (OS), recognized as surrogates for survival. Ten( 10) genes of interest, namely NOTCH1, FGF2, MYC, RB1, ATM, MET, BRCA1, BRCA2, ATM and, VHL, were selected as being highly influenced by epigenetic control. We included 54 patients with reported cDNA on the genes of interest for this study evaluating the predictive impact of early changes in cDNA in response to multitargeted epigenetic treatment and the patient survival. There were 12 cases with NOTCH1 mutations, 20 cases with MYC mutations, 5 cases with RB1, 15 cases with BRCA1 or BRCA2 mutations, 26 cases with FGF2 mutations, 18 cases with MET mutations, 2 with VHL mutations and 2 cases with ATM mutations, for a total of 100 data points. Tests for statistical significance were completed using the Fisher Exact probability test calculator found at vassarstats.net/tab2x2.html. Significance level was set at α = .05. Results: There was statistically significant (p-value: .046) correlation on the response of the allele frequency of the observed NOTCH1 alteration with similar response in the angiogenesis biomarkers (Plasma VEGF) and presence of circulating tumor cells. There was a significant correlation (p-value: .014) between a decrease in AF of the observed MYC alteration and biomarker/imaging response on follow-up. In the group of 26 identified with FGF2 mutations, 22 saw cDNA alteration fraction(AF) reduction post therapy. 16/26 of them had either c Myc or NOTCH1 alterations. Also 8 /18 cases with c Met alterations shared NOTCH1 or Myc alteration. This represents a statistically significant (p-value: .0001) correlation on the response of the allele frequency of the observed FGFR2 alteration with the response of other biomarkers. Conclusions: There were a number of significant correlations observed between early changes in cDNA allele fractions of specific genes and the later observations of established prognostic markers. We conclude that changes in cDNA mutated allele fractions observed in liquid biopsy may provide an early useful independent prognostic marker for tumors carrying epigenetically influenced targets and their alterations.

Eosinophil-cationic protein - a novel liquid prognostic biomarker in melanoma

BackgroundThe role of eosinophils in cancer is not yet completely understood, but patients with eosinophilia show a trend towards longer survival in several types of cancer, including melanoma. However, eosinophil count at initial diagnosis of metastatic melanoma does not predict survival. Since eosinophil cationic protein (ECP) mediates anticancer effects, such as tissue remodelling and cytotoxic activity, we investigated this marker as an early prognostic marker in metastatic melanoma.MethodsSerum of 56 melanoma patients was collected at the time of diagnosis of metastatic disease. ECP levels as measured by ELISA were correlated with overall survival (OS) in patients before systemic therapy with immunotherapy or chemotherapy. Statistical analyses were performed using the Log–Rank (Mantel–Cox) test.ResultsThe median OS for patients with high serum ECP above 12.2 ng/ml was 12 months (n = 39), compared to 28 months for patients with ECP below this threshold (n = 17; p = 0.0642). In patients with cutaneous melanoma, excluding patients with uveal and mucosal melanoma, the survival difference was even more striking (p = 0.0393). ECP’s effect size on OS was observed independently of the consecutive therapy. ECP levels were not correlated with LDH levels.ConclusionECP seems to be a novel prognostic serum marker for the outcome of melanoma patients, which is independent of LDH and easy to perform in clinical practice. The striking negative prognostic value of high ECP level is unanticipated and can guide patient management.

Plasma S100A8/A9 heterodimer is an early prognostic marker of acute kidney injury associated with cardiac surgery.

We investigated whether plasma levels of the inflammation marker S100A8/A9, could predict acute kidney injury (AKI) onset in patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB). Plasma levels of S100A8/A9 and other neutrophil cytosolic proteins were measured in 39 patients pre- and immediately post-CPB. All markers increased significantly post-CPB with S100A8/A9, S100A12 and myeloperoxidase levels significantly higher in patients who developed AKI within 7days. S100A8/A9 had good prognostic utility for AKI, with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.676-0.949) and a cut-off value of 10.6μg/ml (85.7% sensitivity and 75% specificity) irrespective of age. Plasma S100A8/A9 levels immediately after cardiac surgery, can predict onset of AKI, irrespective of age.

Peripheral Blood Platelet to Lymphocyte Ratio as Potential Diagnostic and Prognostic Markers of Acute Cerebral Infarction and its Clinical Significance.

The aim of the present study is to explore the diagnostic and prognostic value of peripheral blood platelet-to-lymphocyte ratio (PLR) in acute cerebral infarction (ACI). We enrolled 121 patients with ACI and 35 healthy volunteers in the present study. The lymphocyte and platelet counts and the platelet-to-lymphocyte ratios of the candidates were calculated, and a receiver-operating characteristic (ROC) curve was drawn to examine whether PLR was a sensitive biomarker for distinguishing ACI patients from the healthy volunteers; moreover, the Glasgow outcome scale (GOS) results of the patients were recorded to evaluate the short-term prognosis of the patients, and the relationship between PLR and GOS were investigated. We observed that the platelet counts were decreased in patients with ACI compared to the healthy volunteers, but no significant differences were observed (p > 0.05). On the other hand, lymphocyte counts were significantly decreased in patients with ACI, and PLR was significantly increased in patients with ACI compared with the healthy controls (p < 0.001). Moreover, the area under the curve (AUC) of platelet counts, lymphocyte counts, and PLR were 0.5365 (95% confidence interval (CI), 0.4373 to 0.6357), 0.7526 (95% CI, 0.6630 to 0.8421), and 0.8320 (95% CI, 0.7586 to 0.9054), respectively, suggesting that PLR was a sensitive biomarker for distinguishing ACI patients from the healthy controls. Finally, the PLR of the patients were negatively correlated with the GOS score of the patients. We reported that PLR was significantly increased in the peripheral blood of patients with ACI, sug-gesting that PLR might be a potential early diagnostic and prognostic marker for ACI.

New markers for odontogenic lesions: role of the Nicotinamide N-methyltransferase

New markers for odontogenic lesions: role of the Nicotinamide N-methyltransferase

2047. Study of Molecular epidemiology, risk factor analysis and comparison of diagnostic methods for rapid diagnosis of fungal pneumonia in critically ill cirrhotics

BackgroundLiver cirrhosis causes immune dysregulation and increased susceptibility to fungal infections. We studiede risk factors, molecular epidemiology and compared the rapid diagnostic methods and biomarkers for fungal pneumonia in critically ill cirrhoticsMethodsSingle-center, prospective cohort study of 50 critically ill cirrhotics with fungal pneumonia between January and September 2017. Comparative analysis of culture, real-time PCR and biomarkers; Bronchoalveolar lavage and serum galactomannan, serum procalcitonin were measured by ELISA and chemiluminescence assay on Days 1, 3, 7. Final outcome were mortality within 1 month after diagnosis or discharge. Genotyping of clinical and air sampling Aspergillus isolates was doneResults Aspergillus flavus was most common species (34/50, 68%). Risk factors were, neutropenia (P 0.03), steroids prior to ICU admission (P 0.02), prolonged hospitalizations >21 days (P 0.05). Culture positivity was 80%. Culture was not inferior to real-time PCR for diagnosis of fungal pneumonia. BAL Galactomannan was early prognostic marker with median rise above >1 index value on Day 1. Median PCT level was higher from Day 1 in the fungal pneumonia nonsurvivor group (3.29 vs. 0.8 ng/mL) with higher 30-day mortality (72%). Higher PCT was associated with bacterial co-infection (48%), antibiotic(74%) and antifungal therapy and renal failure and mortality. Cinical isolates from patients matched those recovered from air in two clusters.ConclusionFungal pneumonia complicates cirrhotics with neutropenia, prolonged hospitalization and steroids as risk factors. Aspergillus species predominate as in Asian epidemiology. Culture methods are reliable and combination of molecular test with BAL galactomannan is useful for rapid diagnosis. SerumPCT is raised in patients with fungal pneumonia and associated with higher mortality. In our study the baseline PCT at admission to ICU was higher in nonsurvivor group, levels on D3 and D7 were persistantly higher. High serum procalcitonin level is an independent prognostic biomarker of mortality risk in fungal pneumonia. Genetic relatedness of clinical and environmental sample necessitates infection control measures to prevent invasive aspergillosis in high-risk patients.Disclosures All authors: No reported disclosures.

What Is the Future of Circulating Tumor Cells in Colorectal Cancer?

To introduce recent progress on circulating tumor cell (CTC) research in colorectal cancer (CRC) and to highlight clinical application of CTCs from detection to assessment of treatment response. CTC biological characteristics in CRC play an important role in the detection of CTCs. The in vitro culture of CTCs from CRC patients (cell lines and organoids) can potentially facilitate rapid drug testing and treatment prediction. CTC detection should be standardized with improved detection rate in CRC; further, clinical investigation is still needed to clarify its potential as a tool for early CRC detection, a predictive and prognostic marker to ultimately guide treatment. Gaining an improved understanding of CTCs characteristics and ultimately, integration of CTC detection and utilization of CTCs may lead to optimized tumor treatment and facilitate precision medicine.

Micro RNA-4651 Serves as a Potential Biomarker for Prognosis When Selecting Hepatocellular Carcinoma Patients for Postoperative Adjuvant Transarterial Chemoembolization Therapy.

Our previous reports have shown that microRNA‐4651 is a potential early diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to investigate whether microRNA‐4651 modified postoperative adjuvant transarterial chemoembolization (pa‐TACE) to improve the prognosis of hepatocellular carcinoma. A hospital‐based retrospective study, including 302 patients with advanced‐stage hepatocellular carcinoma who received tumor resection or tumor resection plus pa‐TACE as an initial therapy, was conducted to assess the effects of microRNA‐4651 on pa‐TACE treatment. MicroRNA‐4651 expression in tumor tissues was tested using the TaqMan‐PCR technique. The sensitivity of tumor cells to doxorubicin (an anticancer drug used in pa‐TACE procedure) was analyzed by the half‐maximal inhibitory concentration (IC50). Upregulated microRNA‐4651 expression in tumor tissues can improve the therapeutic response of patients with hepatocellular carcinoma on pa‐TACE (hazard ratios [95% confidence intervals] = 0.32 [0.22‐0.46] for death risk and 0.39 [0.28‐0.56] for tumor‐recurrence risk, respectively), but downregulated expression cannot. Functional analyses–displayed microRNA‐4651 mimics decreased while its inhibitor increased the IC50 of tumor cells to doxorubicin (0.65 [0.61‐0.69] versus 2.17 [1.98‐2.37] µM). Cytochrome P450 2W1 was shown as a possible target of microRNA‐4651. Additionally, dysregulation of microRNA‐4651 also affected the clinical pathological features of hepatocellular carcinoma and was an independent prognostic factor for this cancer. Conclusion: These results indicate that increasing microRNA‐4651 expression may be beneficial for pa‐TACE in improving hepatocellular carcinoma prognosis.

Estradiol to Androstenedione Ratios Moderate the Relationship between Neurological Injury Severity and Mortality Risk after Severe Traumatic Brain Injury.

Early declines in gonadotropin production, despite elevated serum estradiol, among some individuals with severe traumatic brain injury (TBI) suggests amplified systemic aromatization occurs post-injury. Our previous work identifies estradiol (E2) as a potent mortality marker. Androstenedione (A), a metabolic precursor to E2, estrone (E1), and testosterone (T), is a steroid hormone substrate for aromatization that has not been explored previously as a biomarker in TBI. Here, we evaluated serum A, E1, T, and E2 values for 82 subjects with severe TBI. Daily hormone values were calculated, and E2:A and E1:T ratios were generated and then averaged for days 0-3 post-injury. After data inspection, mean E2:A values were categorized as above (high aromatization) and below (low aromatization) the 50th percentile for 30-day mortality assessment using Kaplan-Meier survival analysis and a multivariable Cox proportional hazard model adjusting for age, and Glasgow Coma Scale (GCS) to predict 30-day mortality status. Daily serum T, E1, and E2 were graphed by E2:A category. Serum E1 and E2 significantly differed over time (p < 0.05); the high aromatization group had elevated levels and a significantly lower probability of survival within the first 30 days (p = 0.0274). Multivariable Cox regression showed a significant E2:A*GCS interaction (p = 0.0129), wherein GCS predicted mortality only among those in the low aromatization group. E2:A may be a useful mortality biomarker representing enhanced aromatization after TBI. E2:A ratios may represent non-neurological organ dysfunction after TBI and may be useful in defining injury subgroups in which GCS has variable capacity to serve as an accurate early prognostic marker.