Early Consolidation Research Articles

Low levels of minimal residual disease after induction chemotherapy for BCR-ABL1-negative acute lymphoblastic leukaemia in adults are clinically relevant.

The aim of the present study was to evaluate the significance of low-level minimal/measurable residual disease (MRD) during early consolidation treatment in adult BCR-ABL1-negative acute lymphoblastic leukaemia. The MRD load was monitored by immunoglobulin/T-cell receptor rearrangements and assessed as negative [complete MRD response (CMR)], positive non-quantifiable (MRDnq) and positive quantifiable (MRDq). MRDnq before the first and second consolidation blocks had a comparable negative effect on survival as MRDq. The 5-year overall survival for CMR, MRDnq and MRDq at week 11 was 74·0%, 42·3% and 35·0% respectively. No central nervous system infiltration and MRD at week 11 were independent prognostic factors for survival on multivariate analysis (hazard ratios 0·32 and 2·25).

Intensification of Early-Phase Therapy to Diminish the Prognostic Effect of Myeloid Antigen Expression in Infants with KMT2A-Rearranged Acute Lymphoblastic Leukemia: A Report from the JPLSG MLL-10 Trial

Background KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL) is a rare and dismal disease in infants. Despite restriction of the indication of allogeneic hematopoietic stem cell transplantation to the high-risk group (patients aged <180 days with KMT2A-r ALL or central nervous system involvement), adoption of an Interfant-06-based induction therapy with stricter age-related dosing followed by COG AALL0631-based post-remission chemotherapy with additional administration of high-dose cytarabine in the early intensification phase led to rapid clearance of minimal residual disease (MRD) in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) MLL-10 trial. The MLL-10 trial demonstrated an improved outcome of 66.2% in 3-year event-free survival (EFS) among infants with KMT2A-r ALL (Tomizawa D. Blood 2021). As the Interfant-06 study showed an association between the expression levels of myeloid markers (MM) and poor MRD clearance at end of induction (EOI) and a high relapse rate (Stutterheim J, J Clin Oncol.2021), we analyzed the significance of MM expression in the MLL-10 cohort and its association with prognosis.MethodsWe analyzed and compared the MM expression (defined as at least one positive marker [with a positive blast subset ≥ 10%] among CD117, CD13, CD33, and CD65/CD15) by using flow cytometry (FCM) in infants with KMT2A-r ALL who were registered in the JPLSG MLL-10 trial. We also compared the results of immunoglobulin/T-cell receptor (Ig/TCR) gene-based polymerase chain reaction (PCR)-MRD analyses or 4-color FCM-MRD assay between the MM-positive and MM-negative groups at EOI and end of early consolidation. The Ig/TCR-MRD results were classified as negative if <5 × 10 −4 and positive if ≥5 × 10 −4, while the FCM-MRD results were classified as negative if <0.01% and positive if ≥0.01%. We prioritized PCR-MRD and used FCM-MRD when we could not make a primer for PCR-MRD. The presence of MRD was not used as a basis for choosing the appropriate therapy.Results and DiscussionAmong the patients with KMT2A-rALL, 74 were included in this study, excluding one who was not evaluated with FCM at diagnosis. Of these patients, 42 were MM-positive and 32 were MM-negative. The 3-year EFS rates of the MM-positive and MM-negative patients were 62.3% (95% confidence interval [CI], 45.5-75.3) and 70.0% (95% CI, 50.3-83.1), respectively (p = 0.61). Their 3-year overall survival rates were 80.6% (95% CI, 65.0-89.8) and 87.5% (95% CI, 70.0-95.1), respectively (p = 0.74). The numbers of MM-positive and MM-negative patients according to age group are summarized in Table 1, and the difference in age distribution between the two groups was not significant. The MRD statuses of the patients at EOI in the two groups are also summarized in Table 1. No significant difference in MRD clearance was found between the MM-positive and MM-negative groups.ConclusionIn this study, we found no significant difference in survival rate between the MM-positive and MM-negative groups. The MM expression was not a prognostic marker in the infants with KMT2A-r ALL in the MLL-10 cohort. We believe that rapid MRD clearance in the early phase of treatment with enhanced chemotherapy would have the greatest contribution to the improvement of prognosis. In this study, the MM-positive patients from the MLL-10 cohort might have benefited from early-phase treatment intensification in terms of MRD clearance. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P163 Slow wave transcranial electrical stimulation during wake to investigate the consolidation of new learning

Abstract Introduction Slow, oscillatory, transcranial electrical stimulation (so-tES) applies a current over the scalp that oscillates in intensity at a frequency associated with slow wave sleep (SWS; 0.75Hz). When applied during SWS, so-tES can enhance SWS EEG power compared to sham stimulation, as well as overnight declarative memory consolidation. When applied during wake, so-tES can enhance local EEG power in the slow wave frequency range (0.5–4.5Hz) compared to sham. Therefore, this study will investigate whether so-tES can enhance the early consolidation of new learning compared to sham, when applied during wake. A preliminary analysis of data will be presented. Methods Healthy, young, right-handed adults (18–35 years) practiced a motor sequence learning task for 30 minutes, before receiving 15 minutes of active or sham so-tES (0.75Hz) during quiet wakefulness. Task performance was assessed by recording the total number of correct sequences performed in 30 seconds before practice, after practice, and after stimulation. Performance improvements will be compared between stimulation conditions. Non-invasive, electrophysiological corticospinal excitability measurements (i.e., motor-evoked potentials) were also recorded at six timepoints throughout each session, to investigate whether active so-tES can modulate corticospinal excitability differently to sham. Progress to date Data collection is ongoing, and completion is expected by late 2021. Intended outcome and impact We expect so-tES to enhance early skill consolidation during wake, and that enhanced consolidation will be associated with less variable measurements of corticospinal excitability, when compared with sham stimulation.

Long-lasting memory no longer means forever: Relationship between accelerated long-term forgetting and autobiographical memory disorders amongst patients with temporal lobe epilepsy

Patients with temporal lobe epilepsy (TLE) have difficulties when they are asked to recall remote autobiographical memory. Also, some patients with epilepsy show accelerated long-term forgetting (ALF) over days or weeks for material demonstrated to have been retained when assessed after typical short-term delays. When remote autobiographical memory has been investigated in patients who show ALF, impairments have been detected in most cases, but the extent to which remote autobiographical memory impairments are explained by early consolidation deficits has not been clarified.

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Asparaginase: Understanding and Overcoming Toxicities

Introduction The extension of pediatric-inspired regimens to young adults with newly diagnosed acute lymphoblastic leukemia (ALL) has considerably improved leukemia outcomes in this population,1–3 and nowadays, more young adults are being cured with chemotherapy and successfully spared from complications of early allogeneic hematopoietic cell transplantation consolidation.4 Pediatric-inspired ALL regimens rely heavily on the use of non-myelosuppressive drugs, such as asparaginase, steroid, and vincristine. Asparaginase, in particular, is a key element for pediatric-inspired regimens, and the inclusion of asparaginase and the more extensive use of it in these regimens has led to better ALL outcomes.5,6 In contrast, a summary of approximately 8,000 children enrolled in the Children’s Oncology Group showed a direct correlation between early asparaginase discontinuation as the result of emerging toxicities and inferior outcomes. 7

Decrease of ARC protein expression in the striatum after tone fear conditioning

Introduction. The involvement of the striatal system in S-R learning is usually based on neural plasticity related to immediate early-genes (IEGs). Previous studies also have shown that the dorsal striatum plays a role in tone fear conditioning (TFC). Objectives. Given that IEg expression in dorsal striatum supports S-R learning we analyzed early molecular consolidation events in the striatum by measuring the protein levels of the EGR1, C-Fos, and Arc in the striatum 30 and 90 minutes after the TFC training. Additionally, to minimize a dorsal hippocampal possible interference, glutamatergic transmission was disrupted during fear conditioning training using the NMDA receptor antagonist AP5 injection into hippocampus. Method. Wistar rats received AP5 or saline injection in the hippocampus five minutes before undergoing tone fear conditioning (tone and foot-shock pairings) or tone only. Results. Animals that received tone and footshock pairings presented a decrease in ARC protein 30 minutes after training when compared to the tone groups. AP5 treated group exposed to tone only condition presented a decrease in EGR protein 90 minutes after training when compared to the saline and tone. No differences were observed in FOS protein levels. Conclusions. Our results suggest that it is possible that some interaction between striatum and hippocampus in processing tone experience and that reduced levels of ARC could be related to the associative features of this pavlovian task.

Clofarabine increases the eradication of minimal residual disease of primary B-precursor acute lymphoblastic leukemia compared to high-dose cytarabine without improvement of outcome. Results from the randomized clinical trial 08-09 of the Cooperative Acute Lymphoblastic Leukemia Study Group.

Novel treatment strategies are needed to improve cure for all children with acute lymphoblastic leukemia (ALL). To this end, we investigated the therapeutic potential of clofarabine in primary ALL in trial CoALL 08-09 (clinicaltrials gov. identifier: NCT01228331). The primary study objective was the minimal residual disease (MRD)- based comparative assessment of cytotoxic efficacies of clofarabine 5x40 mg/m2 versus high-dose cytarabine (HIDAC) 4x3g/m2, both in combination with PEG-ASP 2,500 IU/m2 as randomized intervention in early consolidation. The secondary objective was an outcome analysis focused on treatment arm dependence and MRD after randomized intervention. In B-cell precursor (BCP)-ALL, eradication of MRD was more profound after clofarabine compared to cytarabine, with 93 versus 79 of 143 randomized patients per arm reaching MRD-negativity (c2 test P=0.03, leftsided P [Fisher’s exact test]=0.04). MRD status of BCP-ALL after randomized intervention maintained its prognostic relevance, with a significant impact on event-free survival (EFS) and relapse rate. However, no difference in outcome regarding EFS and overall survival (OS) between randomized courses was observed (5-year EFS: clofarabine 85.7, SE=4.1 vs. HIDAC 84.8, SE=4.7 [P=0.96]; OS: 95.7, SE=1.9 vs. 92.2, SE=3.2 [P=0.59]), independent of covariates or overall risk strata. Severe toxicities between randomized and subsequent treatment elements were also without significant difference. In conclusion, clofarabine/PEG-ASP is effective and safe, but greater cytotoxic efficacy of clofarabine compared to HIDAC did not translate into improved outcomes indicating a lack of surrogacy of post-intervention MRD at the trial level as opposed to the patient level, which hampers a broader implementation of this regimen in the frontline treatment of ALL.

Plate Fixation for Irreducible Proximal Humeral Fractures in Children and Adolescents—A Single-Center Case Series of Six Patients

Background: Recommended treatment for severely displaced proximal humeral fractures in children is the closed reduction and percutaneous fixation by K-wires or intramedullary nailing. Methods: From January 2016 to January 2017 6, 21 children/adolescents (range 8 to 16 years) with proximal humeral fractures were treated surgically for severe displacement. In these six patients, several attempts of closed reduction were unsuccessful, and an open reduction was performed. The humeral head was fixed with a 3.5 mm T-plate without affecting the growth plate. Plate removal was performed at a mean interval of 132 days after initial surgery. Two years after initial surgery, the clinical outcome was assessed by the Constant–Murley score and QuickDASH score (including sport/music and work) and the shoulder joint was evaluated with a standardized sonographic examination for the rotator cuff and the conjoint tendon. Results: In all six patients, dorsal displacement of the fracture was irreducible due to the interposition of tendinous or osseous structures. Intraoperatively, the interposed structures were the long biceps tendon in two, periosteal tissue in two, a bony fragment in one, and the long biceps tendon together with the conjoint tendon in one case. At mean follow-up of 26 months (range 22 months to 29 months), patients showed very good clinical results with an excellent mean Constant–Murley score of 97.5 (range 91 to 100) and mean QuickDASH score (including sport/music and work) of 5.5 (range 0–20.8). An X-ray follow-up 6 weeks after surgery demonstrated early consolidation and correct alignment in all patients. A sonographic evaluation at 2 years post injury showed that the biceps and the conjoined tendon were intact in all patients. Conclusions: If a proximal humeral fracture is not reducible by closed means, a tissue entrapment (most likely biceps tendon) should be considered. Treatment with an open reduction and plate fixation yields very good clinical and radiological results and preserves interposed structures as the biceps and conjoint tendon.

Functional outcome of fracture shaft humerus treated with closed antegrade intramedullary nailing in adults

Background and objectives: The treatment of humeral shaft fractures might include plate osteosynthesis or intramedullary nailing. The fracture hematoma is maintained using intramedullary nails because they are placed in a closed way, allowing for early fracture consolidation and decreased infection rates. Interlocking provides rotational stability, allowing nearby joints to mobilize more quickly. Antegrade nailing, on the other hand, has the side effect of tightening the shoulder. in this study, we wanted to see how humeral shaft fractures treated with closed Antegrade Intramedullary nailing fared in terms of time to union, functional results, and comorbidities. Methods: Twenty adult patients with acute humeral shaft fractures were treated using antegrade closed intramedullary nailing. With an average age of 38.4 yrs., there had been 17 men and 3 females (21-65 yrs.). These patients had tracked for two years as well as the outcomes were assessed. Results: 1 (5%) fracture failed to union after an average consolidation time of 13.78 weeks (11-16 weeks). There were three occurrences of intraoperative fracture comminution (15%) that had no impact on fracture healing. 2 (10%) of the patients experienced nail impingement, 1 (5%) had shoulder stiffness, and 1 (5%) had a superficial infection. Functional outcomes were good in 17 (85%), moderate in 2 (10%), and poor in 1 (5%). Results: 1 (5%) fracture failed to union after an average consolidation time of 13.78 weeks (11-16 weeks). There were three occurrences of intraoperative fracture comminution (15%) that had no impact on fracture healing. 2 (10%) of the patients experienced nail impingement, 1 (5%) had shoulder stiffness, and 1 (5%) had a superficial infection. Functional outcomes were good in 17 (85%), moderate in 2 (10%), and poor in 1 (5%).

Ixazomib-Lenalidomide-Dexamethasone (IRd) Combination before and after Autologous Stem Cell Transplantation (ASCT) Followed By Ixazomib Maintenance Is a Safe and Effective Strategy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Phase 2 Study from the Intergroupe Francophone Du MyéLome (IFM)

Ixazomib-Lenalidomide-Dexamethasone (IRd) Combination before and after Autologous Stem Cell Transplantation (ASCT) Followed By Ixazomib Maintenance Is a Safe and Effective Strategy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Phase 2 Study from the Intergroupe Francophone Du MyéLome (IFM)

Consolidation with Bortezomib, Lenalidomide and Dexamethasone Upgrades the Complete Remission Rate after Autologous Hematopoietic Cell Transplantation in Patients with Multiple Myeloma

Introduction : High-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) is a standard front-line treatment strategy for patients with newly diagnosed multiple myeloma (MM). Unfortunately, almost all the patients will eventually relapse, emphasizing the need for new treatment options or strategies to improve outcomes in these patients. A recent meta-analysis clearly demonstrated that post-transplant lenalidomide maintenance improves overall survival (OS), conflicting results were reported on the benefit of early post-transplant consolidation with bortezomib, lenalidomide, and dexamethasone (VRD). The aim of this study was to assess the effect of VRD consolidation on complete remission (CR) rate at Day100 post ASCT, a surrogate marker for progression free survival (PFS) and OS.Methods: This study was conducted at the American university of Beirut Medical Center, Lebanon. A total of 42 patients newly diagnosed with MM had received ASCT, followed by a total post-transplant treatment consisted of 2 cycles of VRD consolidation and maintenance lenalidomide. These patients were treated and followed between 2011 and 2016. All patients received pre-transplant bortezomib based induction. Of them, 17 (41%) patients had VRD triplet combination. The conditioning regimen consisted of high dose melphalan. The consolidation regimen consisted of bortezomib 1.3 mg/m2 I.V. (days 1, 8, 15 and 22 of each 28-day cycle), lenalidomide 25 mg orally daily for 21 days every 28 days, dexamethasone 20 mg total orally (days 1, 8, 15 and 22 of each 28-day cycle) for a total of 2 cycles. Patients and disease characteristics are summarized in table 1.Results: Median age at transplantation was 55 (41-75) years. Median time from diagnosis to transplant was 5 (3-49) months. The median number of days to reach an absolute neutrophil count more than 500/mm3 post-ASCT was 11 days. VRD consolidation therapy was initiated at a median of 59 (34-201) days from transplantation. In total, 40 (95%) patients completed 2 cycles of VRD without grade 3/4 adverse events. One patient could not receive bortezomib during cycle 2 because of severe peripheral neuropathy. All patients received maintenance with lenalidomide. At time of transplant, only 4 (10%) patients were in complete remission (CR), 25 (59%) patients in very good partial remission (VGPR), and 11 (26%) patients in partial remission. Day 30 evaluation post-transplant, 11 (26%) patients were in CR, 6 (14%) patients in VGPR. Importantly, assessment of disease status at day 100 post-transplant identified 17 (40%) patients in CR. After a median follow up of 26 months, the 2 years PFS was 81% and OS was 92.9%.Conclusion: VRD consolidation significantly upgrades the CR rate after ASCT in patients with MM. These encouraging findings need to be verified and confirmed in prospective randomized trials, establishing a new standard of post-transplant treatment in MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of functional outcome of diaphyseal fractures of shaft humerus treated with closed interlocking nail in adults

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Humeral shaft fractures are those fractures of the diaphysis of the midshaft that do not involve the proximal or distal articular joints. Humerus fractures have a substantial impact on personal function and well‐being and are one of the causes of excessive mortality among the elderly. The aim and objective of the study was to study the functional assessment after interlocking nailing in fractures of shaft humerus.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A retrospective clinical study was done on 20 patients with shaft humerus fractures treated with intramedullary nailing by orthopaedic surgeons at a tertiary care centre in the Department of Orthopaedics, Indian Institute of Medical Science and Research, Noor hospital, Jalna between January 2020 to July 2020 (DASH Score being calculated till January 2021). The DASH score was assessed 6 months post-operative day of surgery.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results: &lt;/strong&gt;For all the operated patients clinical, physiological and ortho-radiological assessment were performed to observe and evaluate fracture stabilization, reduction, fracture healing and callus formation, functional evaluation done with DASH scoring system.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Closed intramedullary nailing is safe and reliable technique to fix humeral shaft fracture. It provides early fracture consolidation, with high union rate, with advantage of early mobilization of the involved limb.&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph− adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Higher post-encoding cortisol benefits the selective consolidation of emotional aspects of memory

Emotional experiences create durable memory traces in the brain, especially when these memories are consolidated in the presence of stress hormones such as cortisol. Although some research suggests cortisol elevation can increase long-term memory for emotional relative to neutral content, the impact of stress and cortisol on the consolidation of emotional and neutral aspects of memories when they are part of the same experience remains unknown. Here, after encoding complex scenes consisting of negative or neutral objects placed on neutral backgrounds, participants were exposed to a psychosocial stressor (or matched control condition) in order to examine the impact of stress and cortisol on early consolidation processes. The next day, once cortisol levels had returned to baseline, specific and gist recognition memory were tested separately for objects and backgrounds. Results indicate that while there was a numerical increase in memory for negative objects in the stress group, higher endogenous cortisol concentrations were specifically associated with decreased memory for the neutral backgrounds originally paired with negative objects. Moreover, across all participants, cortisol levels were positively correlated with the magnitude of the emotional memory trade-off effect. Specifically, while memory for negative objects was preserved, elevated cortisol during early consolidation was associated with decreased memory for neutral backgrounds that were initially paired with negative objects. These memory effects were observed in both the stricter specific measure of memory and the less conservative measure of gist memory. Together, these findings suggest that rather than influencing all aspects of an experience similarly, elevated cortisol during early consolidation selectively preserves what is most emotionally salient and adaptive to remember while allowing the loss of memory for less important neutral information over time.

Polysomnography in the Early Consolidation Phase of Mandibular Distraction as a Tool to Identify Residual Tongue-Based Airway Obstruction and Need for Further Distraction: A Follow-Up Study

Background: The objective of this study was to analyze and report our experience with using polysomnography (PSG) during the early consolidation phase of mandibular distraction osteogenesis (MDO) in patients with Pierre Robin Sequence and associated tongue-based airway obstruction with management decisions informed by the results. The secondary objective was to determine whether pre-operative PSG can predict which patients will have persistent obstructive sleep apnea (OSA) and require additional distraction. Methods: A single-surgeon, retrospective review was performed of all patients who underwent MDO for treatment of tongue-based airway obstruction over an 11-year period. Pre-operative and post-distraction 16-channel overnight bedside PSG was performed on all patients and scored according to the AASM Scoring Manual. Patients who demonstrated persistent OSA underwent further distraction and were reevaluated by PSG after final distraction length was achieved. Results: Pre-operative and post-distraction PSG was obtained and available for analysis in 37 patients. Apnea-Hypopnea Index (AHI) improved from 45.85 ± 34.41 to 9.73 ± 10.85 ( P &lt; .001). There was evidence for persistent, severe OSA in 14 patients (38%) and persistent, moderate OSA in 6 patients (16%) in the early consolidation phase of MDO. Nine of these patients underwent additional distraction and demonstrated symptomatic resolution and quantitative improvement in all PSG measures. The group of patients that underwent additional distraction had significantly more severe baseline OSA as defined by preoperative AHI, oxygen desaturation index (ODI), and percentage of time spent below 90% SpO2. There was no significant difference in patient characteristics or pre-operative symptoms between the 2 groups. Conclusions: PSG can be performed at the bedside at the end of the distraction phase of MDO to assess for residual airway obstruction and inform the need for further distraction. Pre-operative PSG measures can help predict the need for further distraction and aid in operative planning and distractor placement.

Аутологичная трансплантация гемопоэтических стволовых клеток при ВИЧ-ассоциированной плазмобластной лимфоме: клинический случай

Plasmablastic lymphoma (PBL) is a disease that was originally described in 1997 as a distinct subtype of diffuse large B-cell lymphoma (DLBCL), which is more common in patients with HIV infection. It is characterized by extranodal lesions, the most common of which are the oral cavity, digestive tract, and skin3. No generally accepted chemotherapy protocol for the treatment of HIV-associated PBL has been developed. Early consolidation through autologous hematopoietic stem cell transplantation (auto-HSCT) may be a treatment option for advanced patients with concurrent use of highly active antiretroviral therapy (HAART). Disease history. Patient B., 44 years old, with HIV-associated PBL-IV-stage according to AnnArbor with lesions of the alveolar process of the upper jaw, lymph nodes of the neck on the left, bronchopulmonary lymph nodes, and the lower lobe of the right lung, who after 6 courses of chemotherapy according to the standard CHOP regimen, autotransplantation of hematopoietic stem cells was performed in the first remission. Conclusion. Our clinical experience correlates with the few studies on this issue. The patient received stem cell-supported high-dose chemotherapy (HDCT) and his life expectancy is 36 months. Keywords: plasmablastic lymphoma, HIV-associated lymphomas, autologous hematopoietic stem cell transplantation.

A Brief Period of Wakeful Rest after Learning Enhances Verbal Memory in Stroke Survivors.

Accumulating evidence suggests that wakeful rest (a period of minimal cognitive stimulation) enhances memory in clinical populations with memory impairment. However, no study has previously examined the efficacy of this technique in stroke survivors, despite the high prevalence of post-stroke memory difficulties. We aimed to investigate whether wakeful rest enhances verbal memory in stroke survivors and healthy controls. Twenty-four stroke survivors and 24 healthy controls were presented with two short stories; one story was followed by a 10-minute period of wakeful rest and the other was followed by a 10-minute visual interference task. A mixed factorial analysis of variance (ANOVA) with pairwise comparisons was used to compare participants' story retention at two time points. After 15-30 minutes, stroke survivors (p = .002, d = .73), and healthy controls (p = .001, d = .76) retained more information from the story followed by wakeful rest, compared with the story followed by an interference task. While wakeful rest remained the superior condition in healthy controls after 7 days (p = .01, d = .58), the beneficial effect was not maintained in stroke survivors (p = .35, d = .19). Wakeful rest is a promising technique, which significantly enhanced verbal memory after 15-30 minutes in both groups; however, no significant benefit of wakeful rest was observed after 7 days in stroke survivors. Preliminary findings suggest that wakeful rest enhances early memory consolidation processes by protecting against the effects of interference after learning in stroke survivors.

Tracing proto-Rheic - Qaidam Ocean vestiges into the Western Tatra Mountains and implications for the Palaeozoic palaeogeography of Central Europe

Zircon petrochronology from amphibolites and retrogressed eclogites from the basement of the Western Tatra Mountains (Central Western Carpathians) reveals a complex rock evolution. An island-arc related basaltic amphibolite from Žiarska Valley shows three distinct zircon forming events: igneous zircon growth at ca. 498 Ma (Middle/Late Cambrian) and two phases of amphibolite-facies metamorphism at ca. 470 Ma (Early Ordovician) and at ca. 344 Ma (Early Carboniferous). A retrogressed eclogite from Baranèc Mountain records two zircon forming events: metamorphic zircon growth under eclogite-facies conditions at ca. 367 Ma (Late Devonian) and amphibolite-facies metamorphism at ca. 349 Ma (Early Carboniferous). These data contribute towards understanding and correlating major tectonothermal events that shaped the eastern margin of Gondwana in the Early Palaeozoic and its subsequent Variscan evolution. The metabasites record vestiges of two completely independent oceanic domains preserved within the Central Western Carpathians: (1) An Ediacaran to Cambrian oceanic arc related to the proto-Rheic - Qaidam oceans and metamorphosed to amphibolite-facies in the Early Ordovician subduction of the proto-Rheic - Qaidam arc during the Cenerian orogeny (ca. 470 Ma) and (2) Late Devonian oceanic crust related to a back-arc basin (Pernek-type), formed by the opening of the Paleotethys and metamorphosed to eclogite-facies during Devonian subduction (ca. 367 Ma). The common Variscan and later evolution of these oceanic remnants commenced with amphibolite-facies metamorphic overprinting in the Early Carboniferous (amphibolite: ca. 344 Ma; retrogressed eclogite: ca. 349 Ma) related to an Early Variscan consolidation and the formation of Pangea. None of the investigated rocks of the Central Western Carpathians show any evidence of being chronologically or palaeogeographically related to the Rheic Ocean, therefore any prolongation of the Rheic suture from the Sudetes into the Alpine-Carpathian realm is highly problematic. Instead, the Southern and Central Alpine Cenerian orogeny can be traced into the Central Western Carpathians.

Improving consolidation by applying anodal transcranial direct current stimulation at primary motor cortex during repetitive practice

Engagement of primary motor cortex (M1) is important for successful consolidation of motor skills. Recruitment of M1 has been reported to be more extensive during interleaved compared to repetitive practice and this differential recruitment has been proposed to contribute to the long-term retention benefit associated with interleaved practice. The present study administered anodal direct current stimulation (tDCS) during repetitive practice in an attempt to increase M1 activity throughout repetitive practice with the goal to improve the retention performance of individuals exposed to this training format. Fifty-four participants were assigned to one of three experimental groups that included: interleaved-sham, repetitive-sham, and repetitive-anodal tDCS. Real or sham stimulation at M1 was administered during practice of three motor sequences for approximately 20-min. Performance in the absence of any stimulation was evaluated prior to practice, immediately after practice as well as at 6-hr, and 24-h after practice was complete. As expected, for the sham conditions, interleaved as opposed repetitive practice resulted in superior offline gain. This was manifest as more rapid stabilization of performance after 6-h as well as an enhancement in performance with a period of overnight sleep. Administration of anodal stimulation at M1 during repetitive practice improved offline gains assessed at both 6-h and 24-h tests compared to the repetitive practice sham group. These data are consistent with the claims that reduced activation at M1 during repetitive practice impedes offline gain relative to interleaved practice and that M1 plays an important role in early consolidation of novel motor skills even in the context of the simultaneous acquisition of multiple new skills. Moreover, these findings highlight a possible role for M1 during sleep-related consolidation, possibly as part of a network including the dorsal premotor region, which supports delayed performance enhancement.