Persistence of DNMT3A mutations at long‐term remission in adult patients with AML

Mutations in DNMT3A, the gene encoding DNA methyltransferase 3 alpha, have been identified as molecular drivers in acute myeloid leukaemia (AML) with possible implications for minimal residual disease monitoring and prognosis. To further explore the utility of DNMT3A mutations as biomarkers for AML, we developed assays for sensitive detection of recurrent mutations affecting residue R882. Analysis of DNA from 298 diagnostic AML samples revealed DNMT3A mutations in 45 cases (15%), which coincided with mutations in NPM1, FLT3 and IDH1. DNMT3A mutations were stable in 12 of 13 patients presenting with relapse or secondary myelodysplastic syndrome, but were also present in remission samples from 14 patients (at allele frequencies of <1–50%) up to 8 years after initial AML diagnosis, despite the loss of all other molecular AML markers. The mutant DNMT3A allele burden was not related to the clinical course of disease. Cell sorting demonstrated the presence of DNMT3A mutations in leukaemic blasts, but also at lower allele frequencies in T and B‐cells from the same patients. Our data are consistent with the recent finding of preleukaemic stem cells in AML, which are resistant to chemotherapy. The persistence of DNMT3A mutations during remission may have important implications for the management of AML.     

Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection

Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥ 20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan-Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.     

Radiographic diagnosis of the occult hip fracture: Experience in 16 patients

We have benefited from using a simple, time-saving radiographic procedure for more than 5 years which may establish a correct diagnosis in most patients with clinically suspected, but initially occult, hip fractures.     

Dental fear and anxiety scores of a Hungarian population living in the Hungarian-Slovakian border region. A pilot study

The aim of the authors was to investigate whether living as a minority has an influence on the dental fear and anxiety values. In this study 201 volunteers (n = 201, inside border Hungarians 144, outside border Hungarians 57, male 90, female 111; age 8 to 83 years, mean 44 +/- 16 yrs.) were investigated. Our methods included collection of demographic data (gender, age, marital status, profession), and administration of the Hungarian versions of dental fear and anxiety related scales namely: DAS, DAQ, DASQ, DFS, DBS, STAI-S, STAI-T and Expectation Scale. Mean values of the scales were: DAS: 10,34 +/- 3,54; DAQ: 2,3 +/- 1,15; DASQ: 12,58 +/- 4,55; DFS: 40,37 +/- 15,67; DBS: 32,89 +/- 12,94; Expectation Scale: 2,87 +/- 3,56, STAI-S: 39,51 +/- 10,68; STAI-T 41,65 +/- 9,08. The mean scores of all the scales were higher in the case of Hungarians living inside the borders of Hungary. The differences were significant in the case of DAS, DAQ, DASQ and DFS scales (p < 0,05). Data of our study indicate that living as a minority not necessarily leads to the increase of dental fear and anxiety.     

Cortical surface area and IQ in very-low-birth-weight (VLBW) young adults

IntroductionQuantitative MRI measurements have revealed abnormalities in cortical development in children born preterm with very-low-birth-weight (VLBW). These children also have increased risk of cognitive deficits that persist into adulthood. The aim of this study was to investigate cortical surface area in VLBW young adults at age 19 compared with controls and to see whether surface area change was associated with cognitive function in the VLBW group.MethodsThirty-eight VLBW (BW ≤ 1500 g) and 59 control participants were included in the study. Cognitive function was assessed by Wechsler Adult Intelligence Scale (WAIS)-III. The MRI scanning was performed at 1.5 T, and for the morphometric analyses of cortical surface area the FreeSurfer software was used.ResultsReduction in cortical surface area was seen in ventrolateral prefrontal, temporal and parietal regions in the VLBW group. Intelligence quotient (IQ) scores were reduced and correlated with surface area reduction in superior and inferior frontal gyri, and in medial temporal and occipital regions in the VLBW group. Brodmann areas (BAs) included in the group differences and in the IQ correlation in the VLBW group were located to the inferior frontal gyrus (BA 11, 12, 44, 45, 47), isthmus (BA 25), the superior parietal (BA 7), the inferior temporal (BA 20) and the parahippocampal gyri (BA 28, 34, 35, 36, 37). The IQ indices that made the largest contribution to the associations between IQ and surface areal change in the VLBW group were the Working Memory and the Processing Speed indices.ConclusionsOur study indicates that permanent deviations in cortical surface area still present in adulthood may explain the increased prevalence of cognitive impairments in preterm born VLBW individuals.     

Influence of patient characteristics on preventive service delivery and general practitioners’ preventive performance indicators: A study in patients with hypertension or diabetes mellitus from Hungary

Background: Regular primary healthcare (PHC) performance monitoring to produce a set of performance indicators for provider effectiveness is a fundamental method for improving guideline adherence but there are potential negative impacts of the inadequate application of this approach. Since performance indicators can reflect patient characteristics and working environments, as well as PHC team contributions, inadequate monitoring practices can reduce their effectiveness in the prevention of cardiometabolic disorders.

Objectives: To describe the influence of patients’ characteristics on performance indicators of PHC preventive practices in patients with hypertension or diabetes mellitus.

Methods: This cross-sectional analysis was based on a network of 165 collaborating GPs. A random sample of 4320 adults was selected from GP’s patient lists. The response rate was 97.3% in this survey. Sociodemographic status, lifestyle, health attitudes and the use of recommended preventive PHC services were surveyed by questionnaire. The relationship between the use of preventive services and patient characteristics were analysed using hierarchical regression models in a subsample of 1659 survey participants with a known diagnosis of hypertension or diabetes mellitus.

Results: Rates of PHC service utilization varied from 18.0% to 97.9%, and less than half (median: 44.4%; IQR: 30.8–62.5) of necessary services were used by patients. Patient attitude was as strong of an influencing factor as demographic properties but was remarkably weaker than patient socioeconomic status.

Conclusion: These findings emphasize that PHC performance indicators have to be evaluated concerning patient characteristics.