Switching to BCL-6 Negativity in Relapsed Diffuse Large B Cell Lymphoma Correlated with More Aggressive Disease Course

Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6⁺ protein expression into BCL-6⁻ expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6⁻ patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6⁺ and BCL-6⁻ groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.     

Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device

ObjectiveAtrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring.MethodsTwenty-five patients were monitored after an AF ablation procedure using the hand-held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation.ResultsDuring months 1-2, 425 of 2942 hand-held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P < .01) in 15 of 23 patients. Holter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P < .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holter detection by an average of 24 days.ConclusionsWireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring.     

Vestibular evoked myogenic potentials in Bell’s palsy

The aim of the present study was to evaluate vestibular nerve involvement in patients with Bell’s palsy with ocular and cervical vestibular evoked myogenic potentials (oVEMP and cVEMP). Ten patients who were diagnosed with Bell’s palsy and ten healthy controls were included. All patients underwent VEMP recordings within 6 days after their initial presentation. Patients with Bell’s palsy had greater oVEMP asymmetry ratio comparing to healthy controls (?38.4 ± 28.7 % vs ?1.3 ± 19.3 %, p = 0.005). As well N10 latencies of the oVEMP response were prolonged comparing to healthy controls (11.575 vs 9.72 ms). There was no difference in cVEMP asymmetry ratio or latencies between groups. We found no correlation between House–Brackmann grading scale and oVEMP asymmetry ratio (r = 0.003, p = 0.994). There are three possible explanations for increased oVEMP amplitudes on the affected side: (1) oVEMP response on the ipsilateral eye could be contaminated by facial nerve activity (blink reflex); (2) the amplitude of N10-P33 could be affected through the stapedial reflex; and (3) increased oVEMP amplitude could be the consequence of the vestibular nerve dysfunction itself, with prolonged latencies of the N10 oVEMP further supporting this explanation. The results of this study indicate possible involvement of the superior branch of the vestibular nerve in patients with Bell’s palsy.     

Concomitant Reconstruction of Arch Vessels during Repair of Aortic Dissection

Surgery for acute aortic dissection is challenging, especially in cases of cerebral malperfusion. Should we perform only the aortic repair, or should we also reconstruct the arch vessels when they are severely affected by the disease process? Here we present a case of acute aortic dissection with multiple tears that involved the brachiocephalic artery and caused cerebral and right upper-extremity malperfusion. The patient successfully underwent complete replacement of the brachiocephalic artery and the aortic arch during deep hypothermic circulatory arrest, with antegrade cerebral protection. We have found this technique to be safe and reproducible for use in this group of patients.     

Interferon Administered in the Cerebrospinal Space and Its Effect on Rabies in Rabbits

Because combined administration of intramuscular and intravenous interferon has been partially successful in the incubationary treatment of rabies, the effect of direct interferon administration into the cerebrospinal fluid space was tested. After injecting 1,800 U of interferon into the cisterna magna or the lateral ventricle, periodic samples, obtained by cisternal taps, showed that 1 to 5% remained after 24 h, as opposed to the known clearance of interferon from the bloodstream to this level within minutes. The distributions of interferon and (131)I-labeled albumin were similar as demonstrated by kinetics of clearance monitored over 24 h. Beginning with and after experimental infection of rabbits, daily intraventricular injections of one million units of interferon were given for as long as 3 weeks. Interferon was prepared from cell culture fluids after pressure dialysis and chromatography on Sephadex G-100. This intensive treatment did not prevent encephalitis, but prolonged the length of the incubation period by one- to two-thirds. The outcome after intraventricular administration was not as favorable as when one million units equally divided between intramuscular and intravenous injections were given at the time of challenge. Interferon administered in the subarachnoid space in this fashion is apparently inadequate to protect the rabbit against rabies. Its role as an adjunct measure, or other methods of administration in the nervous system, remains to be examined.     

Collection strategies and cryopreservation of umbilical cord blood

The aim of this study was to compare (a) two different umbilical cord blood (UCB) collection methods while the placenta is still in the uterus (in utero), and (b) to evaluate the efficacy of four cryopreservation protocols based on UCB haematopoiestic stem cell (HSC) recovery. We analysed UCB samples collected with our original collection system designed for active Syringe/Flush/Syringe method or by standard in utero method. For comparing different cryopreservation procedures, dimethyl sulphoxide (DMSO) at final concentration of 5 and 10% was used and combined with our own controlled-rate or uncontrolled-rate cryopreservation. A total of 99 samples were collected. A significantly higher UCB volume, total nucleated cell and mononuclear cell were seen following the first collection strategy (n= 49; mean +/- SD, 103 +/- 35.4 mL; 12.34 +/- 5.27 x 10(8); 595 +/- 3.47 x 10(6)) vs. the second strategy (n= 50; 86 +/- 29.3 mL; 9.87 +/- 4.47; 424 +/- 2.82 x 10(6)) respectively (P < 0.01). The discard rate was 14% for the first and 36% for the second collection strategy (P < 0.01). It was shown that the most efficient procedure was the controlled-rate protocol combined with lower (5%) DMSO concentration. Using active Syringe/Flush/Syringe method, we collected UCB with greater volumes and with lower discard rate compared to the standard by gravity technique. The data presented also showed much better recovery of UCB cells when controlled-rate freezing procedure and 5% DMSO were combined.     

Computational and experimental identification of novel human imprinted genes

Imprinted genes are essential in embryonic development, and imprinting dysregulation contributes to human disease. We report two new human imprinted genes: KCNK9 is predominantly expressed in the brain, is a known oncogene, and may be involved in bipolar disorder and epilepsy, while DLGAP2 is a candidate bladder cancer tumor suppressor. Both genes lie on chromosome 8, not previously suspected to contain imprinted genes. We identified these genes, along with 154 others, based on the predictions of multiple classification algorithms using DNA sequence characteristics as features. Our findings demonstrate that DNA sequence characteristics, including recombination hot spots, are sufficient to accurately predict the imprinting status of individual genes in the human genome.