Predictors of hepatitis B surface antigen loss,relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B

Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB.     

Routine application of a novel MLPA-based first-line screening test uncovers clinically relevant copy number aberrations in haematological malignancies undetectable by conventional cytogenetics

Objective

The presence of numerical and/or structural chromosomal abnormalities is a frequent finding in clonal hematopoietic malignant disease, typically diagnosed through routine karyotyping and/or fluorescent in situ hybridization (FISH) analysis. Recently, the application of array comparative genomic hybridization (aCGH) has uncovered many new cryptic genomic copy number imbalances, most of which are now recognized as clinically useful markers of haematological malignancies. In view of the limitations of both FISH and aCGH techniques, in terms of their routine application as a first line screening test, we designed a new multiple ligation-dependent probe amplification (MLPA) probemix for use in addition to classic karyotype analysis.

Methods

A novel MLPA probemix was developed to interrogate copy number changes involving chromosomal regions: 2p23-24 (MYCN, ALK), 5q32-34 (MIR145A, EBF1, MIR146A), 6q21-27, 7p12.2 (IKZF1), 7q21-36, 8q24.21 (MYC), 9p24 (JAK2 V617F point mutation), 9p21.3 (CDKN2A/2B), 9p13.2 (PAX5), 10q23 (PTEN), 11q22.3 (ATM), 12p13.2 (ETV6), 13q14 (RB1, MIR15A, DLEU2, DLEU1), 17p13.1 (TP53), and 21q22.1 (RUNX1/AML1) and was applied to DNA extracted from 313 consecutive bone marrow patient samples, referred for routine karyotype analysis.

Results

More than half of the samples originated from newly investigated patients. We discovered clinically relevant genomic aberrations, involving a total of 24 patients (8%) all with a normal karyotype, which would have remained undiagnosed.

Discussion

Our data clearly indicate that routine application of this MLPA screening panel, as an adjunct to karyotype analysis, provides a sensitive, robust, rapid and low-cost approach for uncovering clinically important genomic abnormalities, which would have otherwise remained undetected.     

Effects of Strength vs. Ballistic-Power Training on Throwing Performance

The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations.

Key points

• Ballistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.
• In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.
• The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.

Key words: Shot put, muscle fibres, ultrasound, ballistic training, muscle mass.     

Image-Guided Radiofrequency Ablation (RFA) of Unresectable Hepatic Tumors Using a Triple-Spiral-Shaped Electrode Needle: Initial Experience in 34 Patients

We evaluated the safety and efficacy of image-guided radiofrequency ablation (RFA) using a triple-spiral-shaped electrode needle for unresectable primary or metastatic hepatic tumors. Thirty-four patients with 46 index tumors were treated. Ablation zone, morbidity, and complications were assessed. The lesions were completely ablated with an ablative margin of about 1 cm. Five patients (14.7%) with a lesion larger than 4.5 cm had local tumor progression after 1 month and were retreated. Hemothorax, as a major complication, occurred in 1 of 34 patients (3.0%) or 1 of 46 lesions ablated (2.2%). RFA using this new electrode needle can be effective in the treatment of large unresectable hepatic tumors.     

Symptomatology of the initial prodromal phase in schizophrenia

The initial prodromal symptoms in schizophrenia were studied in 100 DSM-diagnosed patients and 100 controls. The median number of symptoms in the patients and the controls was 8 (range 2-13) and 0 (range 0-5), respectively. Patients developed symptoms indicating social, occupational, and affective dysfunction, whereas the controls' symptoms included magical content and disturbance in mood. There were significant differences in the frequency of several symptoms appearing in the subtypes. Initial prodromal symptoms were classified into negative, positive-prepsychotic, and positive-disorganization categories. Patients with the disorganized subtype were more likely to have had negative symptoms in the prodromal state, and patients with the paranoid subtype were more likely to have had positive symptoms in the prodromal state. Observation of the course of symptoms from the prodromal to the psychotic state revealed that 58 percent of the symptoms showed increased intensity, 21 percent remained unchanged, 5 percent decreased, 3 percent evolved into other affective difficulties, 9 percent progressed into delusions, 1 percent progressed into hallucinations, and 3 percent disappeared. The Global Assessment of Functioning Scale showed that functioning is differentially affected among the subtypes even in the prodromal phase. These findings provide a better understanding of the initial prodromal state of schizophrenia, the signs and symptoms that best define it, and their prognostic significance.