Predictive Value Of Biomarkers Research Articles

Predictive value of C reactive protein (CRP) in patients with metastatic renal cell carcinoma (mRCC) treated with pembrolizumab (pembro) and axitinib (axi).

716 Background: CRP, a biomarker of systemic inflammation, has been shown to have prognostic value in numerous tumour types, including mRCC. The combination of the immune check inhibitor (ICI), pembro, and vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) axi is one of several internationally approved combination ICI/VEGFR-TKI treatment options. We evaluated the predictive value of biomarkers of systemic inflammation in a real-world cohort of patients with mRCC treated with pembro and axi. Methods: Retrospective data of patients treated with pembro and axi were collected from a regional electronic database from two large cancer centres. Inflammatory biomarkers from routine blood tests (including haemoglobin, neutrophil count, platelets, albumin and CRP) prior to starting treatment were recorded. The IMDC score and modified Glasgow Prognostic Score (combining albumin and CRP) were calculated. The primary end point, progression free survival (PFS), was defined as the time between initiation of treatment and clinical or radiographical progression or death, or censorship. Overall survival, defined as the time between initiation of treatment and death, or censorship was also calculated. Univariate and multivariate analyses were undertaken using Cox Regression model and the relationship between different markers and PFS was assessed using Kaplan-Meier curves. Results: Data were available for 93 patients. 74 pts (80%) had clear cell histology, 19 pts (20%) had non-clear cell and 11 pts (12%) had sarcomatoid component. 46 patients had previous nephrectomy. 15 (16%), 46 (50%) and 32 (34%) pts respectively were classified as favourable, intermediate, and poor risk group as per IMDC score. Median PFS was 10.7 (IQR 4.6-not reached) months after a minimum 12.5 months follow-up. Baseline CRP was recorded in 77 (83%) patients, reflecting current routine clinical guidelines. On univariate analysis, neutrophils (≤7.5x109/L/>7.5x109/L) (p=0.044), platelets (≤400 x109/L/>400x109/L) (p=0.043), CRP (≤10mg/L/>10mg/L) (p=0.001), mGPS (0/1/2) (p=0.004) and IMDC risk group (low/intermediate/poor) (p=0.038) were predictive of PFS. On multivariate analyses only CRP was associated with PFS (HR2.78 (95% CI, 1.42-5.44) (p=0.003). At a 1-year landmark PFS was 62% (CRP ≤10mg/L) v 29% (CRP >10mg/L) (p=0.002). CRP also predicted OS ((HR4.50 (95% CI, 1.58-12.8) (p=0.005)) with 1-year OS 85% (CRP ≤10mg/L) v 59% (CRP >10mg/L) (p=0.002). Conclusions: CRP, a biomarker of systemic inflammation, predicts survival in mRCC patients undergoing combined ICI/VEGF-TKI therapy. Our findings support comparable studies in the mRCC population and routine recording of CRP in patients with mRCC. We advocate further work to validate utilisation of CRP as a prognostic biomarker for mRCC in clinical practice.

The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study.

To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs.

A systematic review of resilient performance in defence and security settings.

A narrative systematic literature review was conducted to explore resilient performance in defence and security settings. A search strategy was employed across a total of five databases, searching published articles from 2001 onwards that assessed performance and optimal function in relation to resilience, in defence and security personnel. Following narrative synthesis, studies were assessed for quality. Thirty-two articles met inclusion criteria across a range of performance domains, including, but not limited to, course selection, marksmanship, land navigation, and simulated captivity. Some of the key findings included measures of mental toughness, confidence, and a stress-is-enhancing mindset being positively associated with performance outcomes. There was mixed evidence for the predictive value of biomarkers, although there was some support for cortisol, dehydroepiandrosterone sulfate (DHEA-S) and neuropeptide-y (NPY), and vagal reactivity. Interventions to improve resilient performance were focused on mindfulness or general psychological skills, with effects generally clearer on cognitive tasks rather than direct performance outcomes in the field. In sum, no single measure, nor intervention was consistently associated with performance over a range of domains. To inform future work, findings from the present review have been used to develop a framework of resilient performance, with the aim to promote theoretically informed work.

Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms – results of the EUROPE trial by EMSCO

The EUROPE phase 2 trial investigated the predictive value of biomarkers on the clinical efficacy of single agent romiplostim (ROM) treatment in patients with lower-risk myelodysplastic neoplasms (LR-MDS) and thrombocytopenia within the ‘European Myelodysplastic Neoplasms Cooperative Group‘ (EMSCO) network. A total of 77 patients with LR-MDS and a median platelet count of 25/nl were included, all patients received ROM at a starting dose of 750 μg by SC injection weekly. Thirty-two patients (42%) achieved a hematologic improvement of platelets (HI-P) with a median duration of 340 days. Neutrophil (HI-N) and erythroid (HI-E) responses were observed in three (4%) and seven (9%) patients, respectively. We could not confirm previous reports that HI-P correlated with baseline endogenous thrombopoietin levels and platelet transfusion history, but SRSF2 mutation status and hemoglobin levels at baseline were significantly linked to HI-P. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response.

Distribution of Pathogens and Predictive Values of Biomarkers of Inflammatory Response at ICU Admission on Outcomes of Critically Ill COVID-19 Patients with Bacterial Superinfections-Observations from National COVID-19 Hospital in Croatia.

Background: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. Methods: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. Results: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. Conclusion: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI.

Biomarkers Association and their Predictive Value in SARS-CoV-2-Infected Hospitalized Patients at a Tertiary Health Care Center

This study investigated the association and predictive value of biomarkers in hospitalized patients with SARS-CoV-2 infection. Coronavirus disease (COVID) infection has been linked to a significant hyperinflammatory immune response described as a “cytokine storm,” which results in organ deterioration and damage. Several studies have shown that cytokine levels, notably interleukin 6, can be used as indicators of COVID-19 disease severity. This hospital-based cross-sectional study was conducted in DMIMS Medical College, Sawangi-Meghe, Wardha, from March 2020 to April 2020. The study population was confirmed adult cases of COVID-19 admitted to the hospital during the study period. A positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or rapid antigen test from a nasopharyngeal swab or other respiratory sample was defined as a confirmed SARS-CoV-2 case. A purposive sampling technique was used and a total of 100 study subjects were enrolled for the study. Our study discovered a link between hematological, coagulation, and inflammatory indicators and infection severity. However, whether these indicators have a mechanistic or causative role in illness progression has to be investigated further.

Optical coherence tomography and imaging biomarkers as outcome predictors in diabetic macular edema treated with dexamethasone implant

In this retrospective, multicenter study, we determined the predictive value of imaging biomarkers in diabetic macular edema (DME) outcomes following dexamethasone (DEX) implant(s). Sixty-seven eyes of 47 patients’ best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography (OCT) before and after intravitreal DEX implants were evaluated. Baseline imaging biomarkers were graded using fundus photography and OCT, and the predictive value of biomarkers for significant treatment effects at six months was analyzed. Six months after 2.0 ± 0.8 (mean ± SD) DEX implants, 35 (52%) and 16 (24%) eyes had CFT reduction ≥ 10% from baseline and decreased to < 300 µm, respectively. BCVA improved ≥ 3 lines in 15 (22%) and remained stable in 38 (57%) eyes. At six months, eyes with severe intraretinal cyst (IRC), abundant hyperreflective dots (HRD), and moderate or severe hard exudate had a significantly higher chance of CFT reduction ≥ 10%. Eyes with abundant HRD at baseline and those underwent three DEX implants were more likely to achieve CFT < 300 µm. Eyes with DME and severe IRC, abundant HRD, or moderate-to-severe hard exudate at baseline were more likely to show a significant reduction in CFT six months after DEX implant.

The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery.

The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery.

Association and predictive value of biomarkers with severe outcomes in hospitalized patients with SARS-CoV-2 infection.

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil–lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.

S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy.

Biomarkers such as calcium channel binding protein S100 subunit beta (S100B), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neuron-specific enolase (NSE) have been proposed to aid in screening patients presenting with mild traumatic brain injury (mTBI). As such, we aimed to characterise their accuracy at various thresholds. MEDLINE, SCOPUS and EMBASE were searched, and articles reporting the diagnostic performance of included biomarkers were eligible for inclusion. Risk of bias was assessed using the QUADAS-II criteria. A meta-analysis was performed to assess the predictive value of biomarkers for imaging abnormalities on CT. A total of 2939 citations were identified, and 38 studies were included. Thirty-two studies reported data for S100B. At its conventional threshold of 0.1μg/L, S100B had a pooled sensitivity of 91% (95%CI 87-94) and a specificity of 30% (95%CI 26-34). The optimal threshold for S100B was 0.72μg/L, with a sensitivity of 61% (95% CI 50-72) and a specificity of 69% (95% CI 64-74). Nine studies reported data for GFAP. The optimal threshold for GFAP was 626pg/mL, at which the sensitivity was 71% (95%CI 41-91) and specificity was 71% (95%CI 43-90). Sensitivity of GFAP was maximised at a threshold of 22pg/mL, which had a sensitivity of 93% (95%CI 73-99) and a specificity of 36% (95%CI 12-68%). Three studies reported data for NSE and two studies for UCH-L1, which precluded meta-analysis. There is evidence to support the use of S100B as a screening tool in mild TBI, and potential advantages to the use of GFAP, which requires further investigation.

Serum troponin I: a potential biomarker of hypoxic-ischemic encephalopathy in term newborns.

This study was intended to evaluate the predictive values of serum procalcitonin (PCT), lactate, creatine kinase (CK-MB), and troponin I on the diagnosis and staging of neonatal hypoxic-ischemic encephalopathy (HIE). We retrospectively retrieved data from electronic medical records at our children's hospital, and we included all term newborns admitted between December 2018 and June 2020 with features of perinatal asphyxia. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure and evaluate the predictive values of biomarkers. p values < 0.05 were set as statistical significance. A total of 201 neonates were included. They were grouped as control (n = 40), mild HIE (n = 105), moderate HIE (n = 36), and severe HIE (n = 20). Serum lactate, PCT, CK-MB, and troponin I levels in severe hypoxic-ischemic brain injury group were significantly higher than those in mild to moderate hypoxic-ischemic brain injury group and control group (p < 0.05). Based on ROC and AUC analysis, troponin I showed highest predictive ability with AUC of 0.904, and sensitivity and specificity of 95.00% and 87.50% respectively. Serum troponin I has a good predictive value for neonatal hypoxic-ischemic encephalopathy after perinatal asphyxia.

High baseline fetuin-A levels are associated with lower atherosclerotic plaque progression as measured by 3D ultrasound

Background and aimsThe glycoprotein fetuin-A has anti-inflammatory effects, increases insulin resistance and plays an important role in calcium metabolism. The aim of our study was to assess the predictive value of fetuin-A on atherosclerotic plaque progression in comparison to the established cardiovascular biomarker high sensitivity C-reactive protein (hsCRP). MethodsIn this prospective, single center-, cohort study, we included 194 patients with at least one cardiovascular risk factor or established cardiovascular disease (CVD). Over a period of 4 years, each patient underwent 3D plaque volumetry of the carotid and femoral arteries on a yearly basis. To evaluate the predictive value of biomarkers in terms of plaque progression, the baseline values of fetuin-A and hsCRP were correlated with the plaque progression from baseline to the last follow up visit. Results171 patients were included in the final analysis. Baseline fetuin-A levels showed a significant negative correlation with plaque progression (r = −0.244; p = 0.001). In contrast, baseline hsCRP levels showed no correlation with plaque progression (r = 0.096, p = 0.20). In the ROC-analysis, fetuin-A had a significantly better predictive value than hsCRP (fetuin-A AUC 0.67; p = 0.001 vs hsCRP AUC 0.49; p = 0.88) with an optimal cut-off value at 712 μg/ml. In patients with high fetuin A levels (>712 μg/ml), a significantly lower plaque progression was observed compared to the group with low fetuin-A levels <712 μg/ml (high fetuin-A 197 mm3 vs. low fetuin-A 279 mm3; p = 0.01) ConclusionsHigher fetuin-A levels appear to predict lower atherosclerotic plaque progression in patients with or at risk of cardiovascular disease.

Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus.

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness.Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function.Results: The analysis of biomarkers from the patients’ CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p < 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ − (−5.505 + 55.314 * ratio of p/T-tau − 1.586 * numbers of combined symptoms). The combined indicators (−5.505 + 0.553 * percentage of p/T-tau − 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively.Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study

BackgroundRoutine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable ‘over treatment’ of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes.MethodsInternational multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score < 7 at 5 min, cord pH < 7.10, emergency delivery for fetal distress, and severe neonatal morbidity.DiscussionThe CEPRA trial will identify whether the CPR is a good indicator for delivery in women with perceived reduced fetal movements.Trial registrationDutch trial registry (NTR), trial NL7557. Registered 25 February 2019.

Predictive biomarkers for negative symptoms in schizophrenia

IntroductionIncreasing evidence shows that impaired neuroplasticity and high inflammation play a crucial role in the pathophysiology of schizophrenia. Prospective studies demonstrated that patients with high inflammation usually have a poor treatment response and clinical practice learns that negative symptoms are challenging to treat. The predictive value of biomarkers for negative symptoms in patients with schizophrenia has sparsely been explored.ObjectivesHere, we investigated whether biomarkers are associated with negative symptoms at baseline, and whether biomarkers could predict negative symptoms after six years in patients with schizophrenia.MethodsWe investigated serum biomarkers in an epidemiological study on schizophrenia (N, baseline=110; N, follow-up=65). Negative symptoms were measured using the Positive and Negative Syndrome Scale. Biomarkers (N=189) were measured with a multi-analyte profiling platform and analysed using linear regression models, adjusted for site, age, gender, ethnicity, anti-inflammatory agents, smoking, cardiovascular disease and diabetes, and adjusted for multiple comparisons (q, Benjamini-Hochberg procedure).ResultsIn particular, decreased platelet-derived growth factor (PDGF) (responsible for proliferation of oligodendrocytes) was associated with more negative symptoms at baseline and follow-up (figure). Several other biomarkers associated with inflammation, neuroplasticity and metabolism correlated with the severity of negative symptoms cross-sectionally and/or prospectively. Figure. Biomarkers for Negative Symptoms in Schizophrenia.ConclusionsAlthough our sample size at follow-up was limited, we feel that these analyses contribute to further research of possible predictive biomarkers for negative symptoms in schizophrenia. During the conference we will elaborate our findings with applied machine learning techniques which might shed more light on the predictive value of biomarkers for negative symptoms in schizophrenia.DisclosureNo significant relationships.

Importance of predictive biomarkers related to Pharmacogenetics in breast cancer and prostate: a systematic review

Pharmacogenetics allows to verify the genetic polymorphisms that influence the success of an oncological pharmacotherapy, therefore, the need for progression in the pharmacogenomic oncological field is evident. This study aims to describe the importance of predictive biomarkers related to pharmacogenetic breast and prostate cancer through a literature review. The search for original articles took place between February and November 2020 in databases such as Pubmed, Scielo, Medline and search directories such as Google Scholar. As for the inclusion criteria, the original articles in English, Portuguese and Spanish published between 2010 and 2020 were included. The search result found 102 articles on the subject, 36 excluded because they were review articles, 22 excluded after reading the abstract and 13 excluded because they did not align with the theme. 31 original articles were selected for which the authors prove the importance of validating independent studies on predictive values ​​of biomarkers for breast and prostate cancer. The conclusion of the analyzed studies suggests that the use of biomarkers makes it possible to predict responses to clinical treatment, appropriate therapeutic conduct where they are associated with better treatment results.

Group testing can improve the cost-efficiency of prospective-retrospective biomarker studies

BackgroundCancer treatment is increasingly dependent on biomarkers for prognostication and treatment selection. Potential biomarkers are frequently evaluated in prospective-retrospective studies in which biomarkers are measured retrospectively on archived specimens after completion of prospective clinical trials. In light of the high costs of some assays, random sampling designs have been proposed that measure biomarkers for a random sub-sample of subjects selected on the basis of observed outcome and possibly other variables. Compared with a standard design that measures biomarkers on all subjects, a random sampling design can be cost-efficient in the sense of reducing the cost of the study substantially while achieving a reasonable level of precision.MethodsFor a biomarker that indicates the presence of some molecular alteration (e.g., mutation in a gene), we explore the use of a group testing strategy, which involves physically pooling specimens across subjects and assaying pooled samples for the presence of the molecular alteration of interest, for further improvement in cost-efficiency beyond random sampling. We propose simple and general approaches to estimating the prognostic and predictive values of biomarkers with group testing, and conduct simulation studies to validate the proposed estimation procedures and to assess the cost-efficiency of the group testing design in comparison to the standard and random sampling designs.ResultsSimulation results show that the proposed estimation procedures perform well in realistic settings and that a group testing design can have considerably higher cost-efficiency than a random sampling design.ConclusionsGroup testing can be used to improve the cost-efficiency of biomarker studies.

High expression of krüppel-like factor 10 or Smad4 predicts clinical benefit of adjuvant chemoradiotherapy in curatively resected pancreatic adenocarcinoma: From a randomized phase III trial

PurposeOur previous studies have demonstrated that Krüppel-like factor 10 (Klf10) modulated tumor radiation resistance and helps to predict clinical outcomes of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate whether the expression levels of Klf10, Smad4 and Runx3 can help predict the benefits of adjuvant chemoradiotherapy (CRT) in resected PDAC. Methods and materialsTissue specimens were collected from 111 patients with curatively resected PDAC who were enrolled into a randomized trial comparing adjuvant gemcitabine with or without CRT. Immunohistochemical expression of biomarkers was quantified by pathologists blinded to patient outcomes through a grading system based on the extent and intensity of staining. The predictive value of biomarkers was analyzed using SAS statistical software. ResultsIn total, 56 and 55 patients received adjuvant gemcitabine alone and additional CRT, respectively. The expression levels of Klf10, Smad4 and postoperative CA19-9 were significantly correlated with overall survival (OS) (p = 0.013, 0.045, and 0.047, respectively). Multivariable analysis showed that the expression level of postoperative serum CA19-9 and tumor tissue Klf10 expression level were significant predictors for OS (p = 0.038, and 0.028, respectively). Patients with high Klf10 or Smad4 (n = 55), had a significantly better local recurrence-free survival (∞ vs 19.8 months; p = 0.026) and a longer OS (33.0 vs 23.0 months; p = 0.12) if they received additional adjuvant CRT than gemcitabine only. The results were similar after adjusted by postoperative level of CA19-9. ConclusionPatients with curatively resected PDAC and a high expression of either Klf10 or Smad4 have high chances of benefiting from adjuvant CRT. Combining Klf10 and Smad4 to predict the benefits of adjuvant CRT in resected PDAC deserves further validation.

Biomarkers to predict staging and treatment response in opioid dependence: A narrative review.

Opioid use disorder is a devastating disorder with a high burden in terms of overdose mortality, with an urgent need for more personalized prevention or therapeutic interventions. For this purpose, the description and validation of biological measures of staging or treatment response is a highly active research field. We conducted a narrative review on the pathophysiology of opioid use disorder to propose staging of the disease and search for research studies proposing or demonstrating the predictive value of biomarkers. We propose a IV stage description of opioid use disorder, from (I) vulnerability stage to (II) disease progression, (III) constituted opioid dependence and were several type of treatments can be applied, to the reach a (IV) modified health state. We classified biomarkers studies according to the stage of the disorder they were intended to predict, and to the three categories of methods they used: anatomical and functional aspects of the brain, genetic/transcriptomic/epigenetic studies, and lastly biomarkers of systemic modifications associated with opioid use disorder, especially regarding the immune system. Most studies predicting Stage III that we reviewed collected data from small samples sizes and were cross-sectional association studies comparing opioid dependent patients and control groups. Pharmacogenetic biomarkers are proposed to predict treatment response. Future research should now emphasize prospective studies, replication in independent samples, and predictive value calculation of each biomarker. The most promising results are multimodal evaluations to be able to measure the state of the brain reward system in living individuals.

A clinical prediction score for transient versus persistent childhood immune thrombocytopenia

Unlabelled Box AbstractBackgroundChildhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models. ObjectiveDevelopment and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP. MethodsPatients with a diagnosis platelet count ≤ 20 × 109/L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets ≥100 × 109/L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors. ResultsIn external validation, the score predicted transient versus persistent ITP at 3 months follow‐up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg). ConclusionThe Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (http://www.itprecoveryscore.org).