Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del(9)(q34);SET-NUP214 rearrangement

SET-NUP214 rearrangement is a recently recognized recurrent chromosomal translocation mostly observed in T-ALL. In order to characterize this rare entity, we performed phenotypic and genetic characterization of SET-NUP214 rearrangement through an investigation of a series of 40 consecutive samples of adult T-ALL that was selected among 229 adult ALL cases during 4 years in a single institution. Four cases (10%) of SET-NUP214 translocation were identified in our study. In all cases, diagnosis of T-ALL was established according to the World Health Organization (WHO) classification, and clonal TCR rearrangements were found. The immunophenotypic markers were indicative of the precursor nature of T lymphoblasts, and they expressed one or both of the myeloid-associated antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex chromosomal aberrations in all four SET-NUP214 rearranged cases and del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional genomic imbalances in addition to deletion 9q34. The genomic breakpoint sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and random nucleotide addition was found in two cases at the site of rearrangement. Our independently derived data set from a single institution confirms previous findings of SET-NUP214 rearrangement, indicates the relatively high incidence of SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive clinical, phenotypic, and genetic characteristics of this entity. Also, our report on genomic breakpoints demonstrates the homogeneity in the localization of the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in this study should provide further areas of interest in investigation of SET-NUP214-mediated leukemogenesis.     

Pilot study on combination of azacitidine and low-dose cytarabine for patients with refractory anemia with excess blast

This study analyzed the outcomes of the combination of azacitidine and low-dose cytarabine in patients newly diagnosed with refractory anemia with excess blast (RAEB). Patients were treated with azacitidine 75 mg/m² for 7 days subcutaneously and cytarabine 20 mg/m² intravenously for 7 days every 28 days. The assigned regimen was repeated for two cycles, then the patients treated with azacytidine alone until progression or allogeneic stem cell transplantation (allo-SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current study. After two cycles of the combination therapy, responses were achieved in nine patients (50.0%): four complete response (CR) (22.2%), one partial response (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four patients (22.2%) progressed to acute leukemia during two cycles of the combination therapy. The 1-year overall survival (OS) was 87.5% for the early response group (responses at two cycles) and 0% for the late response group (responses at four cycles, p = 0.042). Plus, the median survival time was 476 days (range, 37–718 days) for the early response group and 221 days (range, 193–249 days) for the late response group. The 1-year OS was 100% for the patients who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the combination therapy showed promising response rate when compared to treatment with azacitidine alone. However, it was limited in terms of preventing leukemic transformation. Allo-SCT would seem to be the only available treatment that can alter disease progression.     

Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B

AIM: To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B (CHB).METHODS: We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d. The biochemical response, as assessed by serum alanine aminotransferase (ALT) activity, virologic response, as assessed by serum hepatitis B virus DNA (HBV DNA) titer, serologic response, as assessed by hepatitis B e antigen (HBeAg) status, and virologic breakthrough with genotypic mutations were assessed.RESULTS: Two-hundred and fifty-four patients [clevudine (n = 118) vs entecavir (n = 136)] were enrolled. In clevudine-treated patients, the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96 (80.9% and 91.2% in the entecavir group, respectively), the mean titer changes in serum HBV DNA were -6.03 and -6.55 log₁₀ copies/mL (-6.35 and -6.86 log₁₀ copies/mL, respectively, in the entecavir group), and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1% (74.4% and 83.8%, respectively, in the entecavir group). These results were similar to those of entecavir-treated patients. The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine, which was similar to patients treated with entecavir (22.8% and 27.7%, respectively). The virologic breakthrough in the clevudine group occurred in 9 (7.6%) patients at weeks 48 and 15 (12.7%) patients at week 96, which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M. There was no virologic breakthrough in the entecavir group.CONCLUSION: In antiviral-naive CHB patients, long-term treatment outcomes of clevudine were not inferior to those of entecavir, except for virologic breakthrough.     

Decreased endothelial progenitor cells and increased serum glycated albumin are independently correlated with plaque-forming carotid artery atherosclerosis in type 2 diabetes patients without documented ischemic disease

Background:?The aim of the present study was to investigate the serum levels of endothelial progenitor cells (EPCs) in type 2 diabetic patients without documented ischemic disease and the association between EPCs and atherosclerotic plaque formation in the carotid artery. Methods and Results:?A clinic-based, prospective study of type 2 diabetic patients was conducted. A total of 73 subjects were enrolled in this study after cardiac magnetic resonance imaging and ankle-brachial index measurements to exclude patients with ischemic disease. Plaque formation in the carotid artery was measured on ultrasonography. Circulating EPCs (CD34(+)/CD133(+)/CD309(+) cells) were counted on flow cytometry. Compared to subjects without carotid artery plaques, patients with plaques were significantly older (P=0.006) and had decreased EPC count (P=0.027). Serum glycated albumin (GA) level and the GA/glycated hemoglobin ratio tended to decrease in patients with plaques (P=0.091 and 0.067, respectively). Other cardiovascular disease risk factors were not significantly different between the 2 groups. On binary logistic regression analysis old age, low EPC count, and high serum GA level were independently correlated with carotid artery plaque formation. Conclusions:?EPC count and serum GA level appear to be a protective and an aggravating factor for endothelial damage, respectively, and therefore, a reduced EPC count or an increased GA level results in atherosclerotic plaque formation in type 2 diabetic patients. (Circ J?2012; 76: 2273-2279).     

Outcomes of kidney allograft in recipients with kidney disease of unknown etiology

The etiology of renal disease is important because the primary renal pathology may affect the outcomes of kidney allograft with respect to recurrence, rejection, and survival. However, for a significant number of patients who undergo kidney transplantation, the disease etiology is unknown. Here, allograft outcomes for patients with kidney disease of unknown etiology (UEK) at three affiliated Korean hospitals were identified. The incidence of biopsy‐proven acute rejection (BPAR) for UEK was 22.9%, which was similar to the rates for diabetic nephropathy (DN, 24.4%) and IgA nephropathy (IgAN, 20.0%; p = 0.345). The cumulative incidence of post‐transplant glomerulonephritis (PTGN) among patients with UEK was significantly lower than that among patients with IgAN (p < 0.001). Overall graft survival of the UEK group was superior to that of the DN group (hazards ratio 0.39, 95% confidence interval 0.17–0.92, p = 0.030). Preemptive transplantation for UEK significantly reduced the incidence of BPAR (preemptive vs. non‐preemptive 9.6% vs. 30.3%, p = 0.001), but graft survival and recurrence were not affected by preemptive transplantation. The outcomes of kidney transplantation for patients with UEK were not inferior to those for patients with IgAN or DN. Preemptive kidney transplantation may be encouraged for UEK patients.     

Analysis of the characteristics of mouthguards that affect isokinetic muscular ability and anaerobic power

PURPOSE

The purpose of this study was to estimate the effects of occlusal stability to identify action mechanisms of mouthguards, known to have a modulatory effect on limb muscle function.

MATERIALS AND METHODS

This study included 20 male subjects to perform the isokinetic muscle tests and the Wingate anaerobic power test on both knee joints under five closed-mouth conditions: without or with 4 types of mouthguards with thickness of 2 mm based on premolar area: (1) full-coverage, (2) anterior partial-coverage, (3) right posterior partial-coverage, and (4) left posterior partial-coverage. The obtained results were subjected to One-way ANOVA with repeated measures, followed by post hoc test of the contrast method (α=.05).

RESULTS

There was no significant difference between the closed position with and without a full-coverage mouthguard in all variables. However, significant differences were observed between with and without a partial-coverage mouthguard in muscular endurance during extension of the left knee, muscular power and endurance during flexion of the right knee. Additionally, significant differences were found between occlusal states with full- and partial-coverage mouthguards in muscular power and endurance during extension of the left knee.

CONCLUSION

These findings indicate the elevation of vertical dimension by 2 mm or the inducement of occlusal stability had little effect on isokinetic muscle strength and anaerobic performance, while uneven distribution of occlusal force might have some positive effects.     

Cognitive emotion regulation strategies contributing to resilience in patients with depression and/or anxiety disorders

Objective

Research suggests that resilience is associated with favorable treatment outcome in patients with depression and/or anxiety disorders. In this regard, the identification of specific characteristics related to resilience that could provide targets for resilience-enhancement interventions is needed. Since the type of cognitive coping strategies is a possible marker of resilience, we investigated adaptive and maladaptive cognitive emotion regulation strategies contributing to resilience in patients with depression and/or anxiety disorders.

Methods

A total of 230 outpatients with depression and anxiety disorders were consecutively recruited and completed the Cognitive Emotion Regulation Questionnaire, the Connor–Davidson Resilience Scale, the Beck Depression Inventory, and the State Anxiety Inventory. A linear regression model was used to determine which cognitive emotion regulation strategies predicted resilience after controlling for relevant covariates. Additionally, this model of resilience was compared with those of depression and anxiety symptoms.

Results

Adaptive strategies were more strongly correlated with resilience than maladaptive strategies. In the regression model, more use of refocus on planning and positive reappraisal as well as less use of rumination predicted high resilience after controlling for age, gender, marital status, depression, and anxiety. Among these strategies, refocus on planning was the common strategy contributing to resilience and depression.

Conclusion

These results suggested that the cognitive emotion regulation strategies of refocus on planning, positive reappraisal, and less rumination contribute to resilience in patients with depression and anxiety disorders. It might provide potential targets for psychotherapeutic intervention to improve resilience in these patients.