The trigger finger is a common condition of the hand that is treated by family physicians, orthopedic and hand surgeons. The patients suffer from pain, triggering of the finger and may develop a ...flexion contracture of the finger, causing significant functional limitations.
The objectives of this study were to evaluate factors involved in the diagnosis and treatment of this condition, as well as the differences in treatment between specialists.
The different specialists were asked to rate the importance of symptoms, examination and imaging studies regarding the decision to refer a patient for surgery as well as suggest the treatment of a hypothetical patient complaining of typical symptoms.
In the 158 questionnaires collected, the complaint of limited finger range of motion and previous treatment were rated most important. Family physicians stated that age, occupation and rate of recent triggering were considered to be additional important factors (p=.0003). In comparison with hand surgeons, family physicians reported localized tenderness as important, and the need for passive release of the finger locked in flexion as less important (p=.0003). Family physicians were more likely to treat with NSAID p= 0.0002), orthopedic surgeons with steroid injections (p=0.0004 and hand surgeons with surgery (p=0.0001).
According to this survey, we found differences in the acquaintance of physicians of different backgrounds with the clinical staging of trigger finger, specifically, the significance of finger contracture and indications for surgery. This information may guide training of physicians in all fields.
Aim: microRNAs (miRs) have been implicated in many malignancies. Our aim was to identify specific miRNAs that can predict risk of relapse in pediatric acute lymphoblastic leukemia (ALL) patients ...treated on BFM protocols, better than the current risk group stratification. Currently, the main method for risk group stratification is based on the amount of minimal residual disease (MRD) assessed at specific time points by real time quantitative PCR (RQ-PCR).
Material and methods: Following microRNA expression analysis performed on 48 bone marrow samples at diagnosis, we focused on several miRs that correlated with at least 3 of the established prognostic markers in ALL to be validated in a cohort of 138 B-lineage ALL samples. Of the miRs studied, down regulated miR-151-5p and miR-451 and upregulated miR-1290 significantly correlated with outcome.
Results: Low expression of miR-151-5p, miR-451 or of both together resulted in significantly worse relapse free survival (RFS) (56%, 63% and 47%, respectively) compared to RFS rates when either or both miRs were highly expressed (80%, 78% and 78%, respectively) (p=0.007, 0.042 and 0.002, respectively). High expression of miR-1290 resulted in worse RFS compared to those that expressed low levels (54% versus 81%; p=0.014). When combining the 3 miRs, a patient expressing low levels of both miRs and/or high levels of miR-1290 had a RFS of 54% (p=0.004). Furthermore, the expression of the 3 miRs could distinguish within the TEL-AML1 negative cohort two groups; one with 80% and the other with 44% RFS (p=0.004). Multivariate Cox regression analysis identified low expression of both miRs and/or high expression of miR-1290 as an independent prognostic marker in the PCR-MRD non-high risk cohort. Patients expressing abnormal levels of the 3 miRs had a 4.47-fold increased risk for relapse (p=0.037). Deletion of IKZF1 gene is a known adverse prognostic marker in B-lineage ALL. In 85 patients, IKZF1 status was analyzed and 9 patients were found to harbor the deletion. The expression of the 3 miRs could still identify an adverse group of patients with 69% RFS within the group with no deletion (p=0.004). When adding IKZF1 and TEL-AML1 status to the Multivariate analysis in addition to PCR-MRD, the expression of the 3 miRs remained a significant independent marker with a 24 fold increased risk for relapse (p=0.011).
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Conclusion: Our results identify the combination of miR-151-5p, miR-451 and miR-1290 as a novel biomarker for outcome in pediatric B-lineage ALL patients, already at time of diagnosis. This may lead to improved risk group stratification and enable early therapeutic intervention that may result in better RFS.
No relevant conflicts of interest to declare.
Abstract
Aim: microRNAs (miRNAs) have been implicated in many malignancies. Our aim was to identify specific miRNAs that can predict risk of relapse in pediatric acute lymphoblastic leukemia (ALL) ...patients treated on BFM protocols, better than the current risk group stratification. Currently, the main method for risk group stratification is based on the amount of minimal residual disease (MRD) assessed at specific time points by real time quantitative PCR (RQ-PCR).
Material and methods: Following microRNA expression analysis, we decided to focus on miR-151-5p and miR-451 that significantly correlated with known prognostic factors in ALL. Validation was performed by measuring the expression levels of miR-151-5p and miR-451 by RQ- PCR on a cohort of B-lineage ALL patients treated by a Berlin-Frankfurt-Munster (BFM) protocol following exclusion of Philadelphia positive patients (n=123).
Results: Low expression of miR-151-5p, miR-451 or of both together resulted in significantly worse relapse free survival (RFS) (61%, 64% and 43%, respectively) compared to RFS rates when either or both miRNAs were highly expressed (83%, 82% and 82%, respectively) (p=0.023, 0.03 and 0.0001, respectively). Multivariate Cox regression analysis identified low expression of both miRNAs as an independent prognostic marker. Patients expressing low expression levels of both miRs had a 8.8-fold increased risk for relapse (p=0.003). Deletion of IKZF1 gene is a known adverse prognostic marker in B-lineage ALL. In 88 patients, IKZF1 status was analyzed and 9 patients were found to harbor the deletion. The expression of both miRs could still identify an adverse group of patients with only 50% RFS within the group with no deletion (p<0.0003).
Even in a non-BFM treated B-lineage ALL cohort from The Netherlands, the expression levels of both miRs significantly correlated with outcome (p=0.003).
Conclusion: Our results identify miR-151-5p and miR-451 as novel biomarkers for outcome in pediatric B-lineage ALL patients, regardless of treatment protocol. This may lead to improved risk group stratification and better RFS.
Citation Format: Smadar Avigad, Iedan RN Verly, Gertjan JL Kaspers, Jacqueline Cloos, Anat Ohali, Michal Hameiri-Grossman, Keren Shichrur, Eva Fronkova, Jan Trka, Drorit Luria, Yona Kodman, Hadar Mirsky, Dafna Gaash, Marta Jeison, Galia Avrahami, Sarah Elitzur, Gil Gilad, Batia Stark, Isaac Yaniv. Increased risk of relapse in non-high-risk children with pediatric B-lineage acute lymphoblastic leukemia can be predicted at diagnosis by microRNA expression. abstract. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B34.
Abstract 2507
microRNAs (miRNAs) have been implicated in many malignancies. Our aim was to identify specific miRNAs that can predict risk of relapse in pediatric acute lymphoblastic leukemia (ALL) ...patients treated according to BFM protocols already at diagnosis. The current risk group stratification is based on the amount of minimal residual disease (MRD) assessed at specific time points by real time quantitative PCR (RQ-PCR).
Following miRNA expression analysis, we decided to focus on miR-151-5p and miR-451 that significantly correlated with known prognostic factors in ALL. Validation was performed by measuring the expression levels of miR-151-5p and miR-451 by RQ-PCR on bone marrow samples at diagnosis of 101 B-lineage ALL patients excluding Philadelphia positive patients.
Low expression of miR-151-5p, miR-451 or of both together resulted in significantly worse relapse free survival (RFS) (43%, 58% and 38%, respectively) compared to RFS rates when either or both miRNAs were highly expressed (81%, 75% and 75%, respectively) (p=0.001, 0.044 and 0.001, respectively). Moreover, following PCR-MRD stratification, low expression of miR-451 or both miRNAs remained significant within the PCR-MRD medium risk group (p=0.00001) and within the standard group for both miRNAs (p=0.024). Multivariate Cox regression analysis identified low expression of both miRNAs as an independent prognostic marker with 11.7 fold increased risk for relapse (p=0.002). After excluding patients harboring the adverse genetic markers Ikaros deletion and P2RY8-CRLF2 rearrangement, a patient expressing low levels of both miRs had a 35 fold risk to relapse (p=0.005).
Analyzing a non-BFM treated B-lineage ALL cohort from The Netherlands, both miRNAs significantly correlated with outcome (p=0.003).
Our results identify miR-151-5p and miR-451 as novel biomarkers for outcome in pediatric B-lineage ALL patients, regardless of treatment protocol. This may allow earlier and improved risk group stratification already at diagnosis, enabling exploration of early therapeutic interventions.
No relevant conflicts of interest to declare.
We evaluated the effect of insulin-like growth factor (IGF)-I on neuronal cell viability and apoptosis induced by exposure to serum-free (SF) medium and to doxorubicin. In primary neuronal culture, ...IGF-I (0.5–2.0 μg/ml) slightly increased basal cell viability; SF medium tended to decrease viability (20–27%), and addition of IGF-I significantly antagonized this decrease (P< 0.05). In neuroblastoma (NB) SK-N-SH cell culture, IGF-I significantly increased viability (0.05–1.25 μg/ml) (P< 0.005); SF medium decreased it by 75%, and this decrease was prevented by IGF-I (0.5–1.0 μg/ml) (P< 0.005). Flow cytometry studies showed an increased apoptosis on exposure to SF medium (88.8 vs 10.2%), which was suppressed to 38.3% by addition of IGF-I. Growth hormone (1–10 μU/ml) did not modify basal cell viability in either culture, and SF-induced cell death in NB cells. Doxorubicin (1–100 μM) caused neurotoxicity in primary and NB cultures (66–39% and 39–10% of controls, respectively), and increased apoptosis in NB cells (73.8 vs 20.1%). IGF-I antagonized these neurotoxic/apoptotic effects (P< 0.05). This study suggests that IGF-I possesses a potent neuroprotective activity which may be involved in the resistance to doxorubicin.
