PREDICT-IV
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PROVIDER: S-DIXA-095 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:PurposeWell-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis.MethodsAge, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival.ResultsMean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p < 0.01) at EOF. We identified an NEP-D = 116 as the cutoff that significantly predicts survival. No gender differences were identified.ConclusionsIn our series, we confirmed NEP-Score applicability. In addition, we propose NEP-D as a simple, quick and cheap prognostic score that can help clinicians in decision making. NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy.
| S-EPMC8124053 | biostudies-literature
Project description:Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (β = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (β = -3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes.
| S-EPMC4622733 | biostudies-literature
Project description:To develop clinical nomograms for prediction of overall survival (OS) and cancer-specific survival (CSS) in patients with stage IV tongue squamous cell carcinoma (TSCC) after surgery based on the Surveillance, Epidemiology, and End Results (SEER) program database.We collected data of resected stage IV TSCC patients from the SEER database, and divided them into the training set and validation set by 7:3 randomly. Kaplan-Meier analysis and Cox regression analysis were adopted to distinguish independent risk factors for OS and CSS. Clinical nomograms were constructed to predict the 3-year and 5-year probabilities of OS and CSS for individual patients. Calibration curves and Harrell C-indices were used for internal and external validation.A total of 1550 patients with resected stage IV TSCC were identified. No statistical differences were detected between the training and validation sets. Age, race, marital status, tumor site, AJCC T/N/M status, and radiotherapy were recognized as independent prognostic factors associated with OS as well as CSS. Then nomograms were developed based on these variables. The calibration curves displayed a good agreement between the predicted and actual values of 3-year and 5-year probabilities for OS and CSS. The C-indices predicting OS were corrected as 0.705 in the training set, and 0.664 in the validation set. As for CSS, corrected C-indices were 0.708 in the training set and 0.663 in the validation set.The established nomograms in this study exhibited good accuracy and effectiveness to predict 3-year and 5-year probabilities of OS and CSS in resected stage IV TSCC patients. They are useful tools to evaluate survival outcomes and helped choose appropriate treatment strategies.
| S-EPMC6616315 | biostudies-literature
Project description:BackgroundSeveral risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.Patients and methodsA retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.ResultsTwo hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.ConclusionIn stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.
| S-EPMC5388376 | biostudies-literature
Project description:No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy; n = 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (n = 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (n = 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.
| S-EPMC5920017 | biostudies-literature
Project description:PREDICT: Omics-based models for prediction of hybrid performance in oilseed rape
| PRJEB63226 | ENA
Project description:Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment 'high' vs. 'low' C11-AMT SUVmax of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.
| S-EPMC10142396 | biostudies-literature
Project description:BackgroundNon-elective cholecystectomies can lead to severe postoperative complications and mortality. Existing risk prediction tools do not meet the need to reliably predict these complications.MethodsUsing the 2011-2016 American College of Surgeons National Surgical Quality Improvement Program datasets, we identified patients undergoing non-elective cholecystectomy with primary ICD 9/10 codes indicating the following diagnoses: symptomatic cholelithiasis, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and cholangitis. We randomly allocated patients to derivation and validation cohorts (80/20 split). Severe complications (Clavien-Dindo grades IV and V) included unplanned intubation, prolonged mechanical ventilation, pulmonary embolism, acute renal failure requiring dialysis, stroke, myocardial infarction, cardiac arrest, septic shock, and mortality. Logistic regression using backward selection identified predictors of severe complications and a risk score was generated based on this model.ResultsOf 68,953 patients in the derivation cohort, 1.7% (N = 1157) suffered severe complications. The final multivariable risk score model included the following predictors: age (0-12 points), preoperative sepsis (5 points), planned open procedure (5 points), estimated glomerular filtration rate (0-13 points), and preoperative albumin level (0-8 points). The associated risk-score model yielded scores from 0 to 43 with 0.1-59.4% predicted probability of severe complications and had a C-statistic of 0.845 (95% CI 0.834, 0.857) in the derivation cohort and 0.870 (95% CI 0.851, 0.889) in the validation cohort.ConclusionA simple risk-score model predicts severe complications in patients undergoing unplanned cholecystectomy for common indications encountered in an acute care surgery service and identifies high-risk patients.
| S-EPMC7415492 | biostudies-literature
Project description:Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were divided into groups of fast, intermediate or non-progressors towards RC (<1 year, 3-5 years or no advanced fibrosis >5 years after LT), assessed by follow-up liver biopsies. Markers of interstitial matrix type III and V collagen formation (PRO-C3 and PRO-C5), basement membrane type IV collagen formation (PRO-C4) and degradation (C4M) were assessed in serum samples collected 3, 6 and 12 months post-LT using specific ELISAs. PRO-C3, PRO-C4, and C4M were elevated in fast progressors compared to non-progressors 3 months after LT. C4M and PRO-C4 additionally differentiated between intermediate and fast progressors at 3 months. PRO-C3 was best predictor of survival, with LT patients in the highest PRO-C3 tertile having significantly shorter survival time. This shows that interstitial matrix and basement membrane remodeling in RC may be distinguishable. Markers originating from different sites in the extracellular matrix could be valuable tools for a more dynamic monitoring of patients at risk of RC. However, this needs validation in larger cohorts.
| S-EPMC6796007 | biostudies-literature
Project description:Background Since numerous retrospective studies and prospective trials have shown divergent results, whether the surgical excision of the primary tumor results in survival benefits for de novo stage IV breast cancer patients is inconclusive. Consequently, we need a prediction model of prognosis, judge the efficiency of breast surgery, and identify the advanced breast cancer patients who would benefit from surgery. Methods We analyzed the data of 2,747 metastatic breast cancer patients (the surgery group) and 4,508 patients (the non-surgery group) from the Surveillance, Epidemiology, and End Results (SEER) database during 2010–2015. Propensity score matching (PSM) was used to attain a balance between the covariates of both groups. We then assessed the potential risk factors for the breast cancer-specific survival (BCSS) of patients in the non-surgery group by Cox regression and constructed a nomogram to predict BCSS. All the patients were classified into different risk groups based on the median risk score obtained from the nomogram. The hazard ratios of BCSS and overall survival (OS) of patients in the two groups were calculated. Results After PSM, 2,288 patients severally in the two groups (the surgery group and the non-surgery group) were enrolled in the study. A nomogram incorporating 13 potential risk factors (i.e., age, race, cohabitation status, income, tumor grade, histotype, tumor size, lymph node status, molecular subtype, metastasis to brain, liver, lung, and chemotherapy) was constructed using the data of patients in the non-surgery group. The C statistics for the internal (patients in the non-surgery group) and external (patients in the surgery group) validation of the nomogram were 0.70 [95% confidence interval (CI), 0.69–0.71] and 0.73 (95% CI, 0.72–0.74), respectively. In the low-risk group, patients in the surgery group had lower risks of breast cancer-specific mortality (BCSM) (hazard ratio =0.53; 95% CI, 0.47–0.59; P for interaction =0.014) and overall mortality (OM) (hazard ratio =0.52; 95% CI, 0.46–0.58; P for interaction =0.002) than those in the non-surgery group. Conclusions Breast surgery might improve the survival of metastatic breast cancer patients in the low-risk group. The established nomogram could provide a reference for clinicians in enabling personalized treatment among advanced breast cancer patients.
| S-EPMC9346227 | biostudies-literature