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1.
Artigo em Inglês | MEDLINE | ID: mdl-31446489

RESUMO

PURPOSE: To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. RESULTS: 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). CONCLUSIONS: CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.

2.
Bone Marrow Transplant ; 54(Suppl 2): 743-748, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431703

RESUMO

We review current approaches in HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for pediatric patients with hemoglobinopathies with a focus on recent developments using TCRα/ß+/CD19+ depleted grafts in patients with ß-thalassemia major (TM) or sickle cell disease (SCD) in two European transplant units. Eleven TM and three SCD patients (Roma cohort) received a preparative regimen consisting of busulfan/thiotepa/cyclophosphamide/ATG preceded by fludarabine/hydroxyurea/azathioprine. The preparative regimen for 5 SCD patients included treosulfan/thiotepa/fludarabine/ATG (Berlin pilot cohort). All grafts were PBSC engineered by TCR-α/ß+/CD19+ depletion. In both cohorts, rates for graft failure, treatment related mortality (TRM) and GvHD were encouraging. Overall survival (OS) and disease-free survival (DFS) in the Roma cohort were 84 and 69%, respectively, while OS and DFS are 100% in the Berlin cohort. Immune reconstitution was satisfactory. Although asymptomatic viral reactivation was common, no severe viral infection occured. These data confirm that TCR-α/ß+/CD19+ depletion is a well-suited haplo-HSCT strategy for children with hemoglobinopathies. We discuss the results in the context of additional optimization strategies and introduce our concepts for multicenter trial protocols in Germany.

3.
Bone Marrow Transplant ; 54(Suppl 2): 689-693, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431707

RESUMO

Posttransplant relapsed B-cell precursor ALL can be cured by 2nd hematopoietic stem cell transplantation (HSCT) in 20% of patients. The major cause of death after second HSCT is leukemic relapse. One reliable predictor for survival after 2nd-HSCT are posttransplant MRD levels. Patients with detectable or increase of MRD are likely to relapse. Patients in complete molecular remission show the best leukemia-free survival and lowest cumulative incidence (CI) of relapse. As patients who undergo second or subsequent HSCT are high-risk patients, we evaluated the prophylactic use of the chimeric Fc-optimized CD19-4G7SDIE-mAb. Posttransplant relapsed CD19+ BCP-ALL patients, who underwent a second or subsequent haplo-HSCT from a T- and B-cell depleted graft received posttransplant prophylactic CD19-4G7SDIE-mAb treatment on compassionate use in complete molecular remission, to increase the antileukemic activity of the new reconstituting immune system by recruiting Fc-expressing effector cells. NK cells recovered early and robust. The 3 year overall survival in 15 evaluable patients was 56%, the 3 year event-free survival was 55% and the CI of relapse 38%. Compared to a historical control group, the CI of relapse was markedly lower and consecutively the EFS higher. Posttransplant-targeted therapy may overcome the need for unspecific GvL effect of undesired GvHD, that can cause severe morbidity and mortality. Due to a low adverse event profile the CD19-4G7SDIE-mAb may be suitable for broad administration to consolidate posttransplant MRD negativity.

4.
Bone Marrow Transplant ; 54(Suppl 2): 727-732, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431711

RESUMO

Posttransplant treatment strategies are narrowed by the vulnerability of bone marrow. Building on immune cells with antitumor activity is a growing field in cancer therapy. Thus, transfer of expanded and preactivated immune cells is a promising intensification of treatment in high-risk tumor patients. We tested ex vivo expanded NK-, γδT-, and CIK cells that were generated by coincubation with irradiated K562-mb15-41BBL and Il2 and compared the expansion conditions of PBMCs versus CD3-depleted PBMCs as well as static versus semi-automated expansion. The median fold expansion was significantly higher using PBMCs and static expansion conditions. Expanded cells were preactivated with a CD56brightCD69high immunophenotype exerting excellent direct cellular cytotoxicity as well as ADCC in various tumor entities. We established a large-scale clinical-grade ex vivo expansion and activation protocol of NK-, γδT-, and CIK cells from donor-derived PBMCs of patients after haploidentical HSCT. In a patient with AML, NK/γδT/CIK cell transfer was associated with MRD response. A significant increase of direct antitumor activity and ADCC post cell transfer was documented. The results that we report here provide the rationale for clinical testing of expanded, preactivated NK/γδT/CIK cells for cancer therapy.

5.
Cytotherapy ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31351799

RESUMO

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in childhood and adolescence. Although some patients present with distinct genetic alterations, such as mutated TP53 or MYC amplification, pediatric medulloblastoma is a tumor entity with minimal mutational load and low immunogenicity. METHODS: We identified tumor-specific mutations using next-generation sequencing of medulloblastoma DNA and RNA derived from primary tumor samples from pediatric patients. Tumor-specific mutations were confirmed using deep sequencing and in silico analyses predicted high binding affinity of the neoantigen-derived peptides to the patients' human leukocyte antigen molecules. Tumor-specific peptides were synthesized and used to induce a de novo T-cell response characterized by interferon gamma and tumor necrosis factor alpha release of CD8+ cytotoxic T cells in vitro. RESULTS: Despite low mutational tumor burden, at least two immunogenic tumor-specific peptides were identified in each patient. T cells showed a balanced CD4/CD8 ratio and mostly effector memory phenotype. Induction of a CD8-specific T-cell response was achieved for the neoepitopes derived from Histidine Ammonia-Lyase (HAL), Neuraminidase 2 (NEU2), Proprotein Convertase Subtilisin (PCSK9), Programmed Cell Death 10 (PDCD10), Supervillin (SVIL) and tRNA Splicing Endonuclease Subunit 54 (TSEN54) variants. CONCLUSION: Detection of patient-specific, tumor-derived neoantigens confirms that even in tumors with low mutational load a molecular design of targets for specific T-cell immunotherapy is possible. The identified neoantigens may guide future approaches of adoptive T-cell transfer, transgenic T-cell receptor transfer or tumor vaccination.

6.
Am J Hematol ; 94(8): 880-890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31095771

RESUMO

Severe infections (SI) significantly impact on non-relapse mortality after hematopoietic stem cell transplantation (HSCT). We assessed 432 children and adolescents with acute lymphoblastic leukemia (ALL) after total body irradiation based myeloablative HSCT within the multicenter ALL-BFM-SCT 2003 trial for SI grade 3 or higher according to common terminology criteria for adverse events. A total 172 patients experienced at least one SI. Transplantation from matched unrelated donors (MUD) was associated with any type of SI in the pre-engraftment period (hazard ratio [HR]: 2.57; P < .001), and with any SI between day +30 and + 100 (HR: 2.91; P = .011). Bacterial (HR: 2.24; P = .041) and fungal infections (HR: 4.06; P = .057) occurred more often in the pre-engraftment phase and viral infections more often before day +30 (HR: 2.66; P = .007) or between day +30 and + 100 (HR: 3.89; P = .002) after HSCT from MUD as compared to matched sibling donors. Chronic GvHD was an independent risk factor for any type of SI after day +100 (HR: 2.57; P < .002). We conclude that allogeneic HSCT from MUD in children and adolescents with pediatric ALL is associated with higher infection rates, which seems attributable to an intensified GvHD prophylaxis including serotherapy and methotrexate.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31089288

RESUMO

Despite significant improvements in the supportive care, sickle cell disease (SCD) leads to significant morbidity and mortality. Allogeneic hematopoietic stem cell transplantation (HSCT), the only curative option, is limited due to matched donor availability. This could be met with T-cell-depleted haploidentical HSCT. Twenty advanced-stage SCD patients, median age 15 years, and 9 patients, median age 14 years, were transplanted with CD3/CD19- or TCRαß/CD19-depleted grafts and from matched sibling donors (MSDs). The conditioning consisted of ATG, thiotepa, fludarabine, and treosulfan. The median follow-up in the T-haplo-HSCT and the MSD patients was 21 (9-62) and 25 (7-60) months, respectively. The OS in the T-haplo-HSCT and MSD was 90% and 100%, respectively. In the T-haplo-HSCT group, two patient succumbed to a CMV pneumonitis and a macrophage activation syndrome (MAS). One patient in the T-haplo-HSCT group requires renal replacement therapy because of BK virus nephritis. None developed grade III-IV acute GvHD. In the T-haplo-HSCT and in the MSD, 20% and 22%, respectively, developed a mild or moderate chronic GvHD. These results demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT also for adult advanced stage SCD patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31089287

RESUMO

Although allogeneic hematopoietic stem-cell transplantation (HSCT) provides high cure rates for children with high-risk acute lymphoblastic leukaemia (ALL), relapses remain the main cause of treatment failure. Whereas donor killer cell immunoglobulin-like receptor (KIR) genotype was shown to impact on relapse incidence in adult myeloid leukaemia similar studies in paediatric ALL are largely missing. Effect of donor KIR genotype on transplant outcome was evaluated in 317 children receiving a first myeloablative HSCT from an HLA-matched unrelated donor or sibling within the prospective ALL-SCT-BFM-2003 trial. Analysis of donor KIR gene polymorphism revealed that centromeric presence and telomeric absence of KIR B haplotypes was associated with reduced relapse risk. A centromeric/telomeric KIR score (ct-KIR score) integrating these observations correlated with relapse risk (hazard ratio (HR) 0.58; P = 0.002) while it had no impact on graft-versus-host disease or non-relapse mortality. In multivariable analyses ct-KIR score was associated with reduced relapse risk (HR 0.58; P = 0.003) and a trend towards improved event-free survival (HR 0.76; P = 0.059). This effect proved independent of MRD level prior to HSCT. Our data suggest that in children with ALL undergoing HSCT after myeloablative conditioning, donor selection based on KIR genotyping holds promise to improve clinical outcome by decreasing relapse risk and prolonged event-free survival.

9.
Psychophysiology ; : e13349, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30861143

RESUMO

Exposure to traumatic events is not unique to post-traumatic stress disorder (PTSD) and is a significant factor in the development of physical and mental disease across the diagnostic spectrum. Using fMRI, this study assesses functional activation in the amygdala and visual cortex during emotional scene processing in a sample of anxiety and mood disorder patients (N = 162). Replicating previous studies with healthy young participants, a strong covariation was found between functional activity in the amygdala and ventral visual cortex, with blood-oxygen-level dependent (BOLD) activity overall significantly enhanced in both regions when viewing emotionally arousing, compared to neutral, scenes. BOLD changes during emotional processing predicted questionnaire reports of experienced trauma and PTSD-like symptoms (e.g., intrusive thoughts, bad dreams, re-experiencing) and associated functional impairment. Patients showing the smallest BOLD changes when viewing emotional (compared to neutral) scenes in the amygdala and ventral visual cortex reported the highest trauma scores, whereas those patients with the largest amygdala emotional reactivity differences reported the lowest trauma scores. Experiencing a life-threatening event (to self or other) that prompts high fear, distress, and functional impairment was associated with reduced functional limbic-visual activity, independent of a PTSD diagnosis. The findings suggest that experienced trauma may be a transdiagnostic vulnerability factor contributing significantly to psychopathology in many patients with anxiety and mood disorders.

10.
Langmuir ; 35(4): 1000-1007, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30607956

RESUMO

In this study, we investigated the thermodiffusion behavior of a colloidal model system as a function of the Debye length, λDH, which is controlled by the ionic strength. Our system consists of an fd-virus grafted with poly(ethylene glycol) (PEG) with a molecular mass of 5000 g mol-1. The results are compared with recent measurements on a bare fd-virus and with results of PEG. The diffusion coefficients of both viruses are comparable and increase with the increasing Debye length. The thermal diffusion coefficient, DT, of the bare virus increases strongly with the Debye length, whereas DT of the grafted fd-virus shows only a very weak increase. The Debye length dependence of both systems can be described with an expression derived for charged rods using the surface charge density and an offset of DT as adjustable parameters. It turns out that the ratio of the determined surface charges is inverse to the ratio of the surfaces of the two systems, which means that the total charge remains almost constant. The determined offset of the grafted fd-virus describing the chemical contributions is the sum of DT of PEG and the offset of the bare fd-virus. At high λDH, corresponding to the low ionic strength, the ST values of both colloidal model systems approach each other. This implies a contribution from the polymer layer, which is strong at short λDH and fades out for the longer Debye lengths, when the electric double layer reaches further than the polymer chains and therefore dominates interactions with the surrounding water.

11.
Int J Radiat Oncol Biol Phys ; 104(1): 137-143, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30593907

RESUMO

PURPOSE: This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation. METHODS AND MATERIALS: Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors. RESULTS: After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported. CONCLUSIONS: In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.

12.
Soft Matter ; 14(45): 9232-9242, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30417915

RESUMO

We performed total internal reflection microscopy (TIRM) experiments to determine the depletion potentials between probe spheres and a flat glass wall which are induced by long and thin, rod-shaped colloids (fd-virus), and probe the spatially resolved dynamics of the probe spheres. The dynamic information from the same raw TIRM intensity time traces is extracted in three different ways: by determining the spatially averaged diffusion constant of the probe sphere normal to the wall, by measuring the position dependence of the diffusion coefficient, and by measuring the particle's local drift velocity. Up to a concentration of about 6 times the overlap concentration of the rod-like colloids, the spatially averaged diffusion coefficient and the amplitude of the depletion potential are in surprisingly good agreement with theoretical predictions in which mutual interactions between the rods are neglected, that is, where the concentration is less than the overlap concentration. On increasing the depletant content even further, however, both the static and the averaged dynamic quantities begin to deviate from such theoretical predictions. In particular we find large deviations from the prediction by Mao, Cates, and Lekkerkerker [J. Chem. Phys., 1997, 106, 3721] based on the third order virial expansion for the rod concentration. It is shown that there are significant inaccuracies in TIRM measurements of diffusion coefficients due to the limited time range in which the mean squared displacements vary linearly in time, whereas mean displacements give much more accurate information concerning the probe sphere dynamics.

13.
Am Surg ; 84(2): e80-e81, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30454487
14.
Br J Haematol ; 183(1): 104-109, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30028016

RESUMO

Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Münster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10·3 years (range 0·5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12·4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs. <10 years: hazard ratio (HR) 3·73, P = 0·009; >15 years vs. <10 years: HR 5·46, P = 0·001], diagnosis of sON prior to HSCT and chronic graft-versus-host disease (yes versus no: HR 2·696, P = 0·015) as significant independent risk factors for the development of sON.

15.
Int J Radiat Biol ; 94(11): 1017-1026, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30028637

RESUMO

PURPOSE: Automated detection of dicentric chromosomes from a large number of cells was applied to study age-dependent radiosensitivity after in vitro CT exposure of blood from healthy donors. MATERIALS AND METHODS: Blood samples from newborns, children (2-5 years) and adults (20-50 years) were exposed in vitro to 0 mGy, 41 mGy and 978 mGy using a CT equipment. In this study, automated scoring based on 13,000-31,000 cells/dose point/age group was performed. Results for control and low dose points were validated by manually counting about 26,000 cells/dose point/age group. RESULTS: For all age groups, the high number of analyzed cells enabled the detection of a significant increase in the frequency of radiation induced dicentric chromosomes in cells exposed to 41 mGy as compared to control cells. Moreover, differences between the age groups could be resolved for the low dose: young donors showed significantly increased risk for induced dicentrics at 41 mGy compared to adults. CONCLUSIONS: The results very clearly demonstrate that the automated dicentric scoring method is capable of discerning radiation induced biomarkers in the low dose range (<100 mGy) and thus may open possibilities for large-scale molecular epidemiology studies in radiation protection.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30047478

RESUMO

BACKGROUND: The National Institute of Mental Health Research Domain Criteria initiative encourages a search for dimensional biological measures of psychopathology unconstrained by current diagnostic categories. Consistent with this aim, the presented research studies a large sample of anxiety and mood disorder patients, assessing differences in principal diagnoses and comorbidity patterns, clinicians' ratings, and questionnaire measures of negative affect and life dysfunction as they relate to a potential brain marker of pathology: the amplitude of the event-related potential (ERP) elicited by a startle-evoking stimulus. METHODS: Patients seeking evaluation or treatment for anxiety and mood disorders (N = 208) participated in two tasks at the University of Florida (Gainesville, FL): 1) imagining emotional and neutral events and 2) viewing emotional and neutral pictures while acoustic startle probes were presented and the ERP was recorded. For a comparison patient group (N = 120), startle probes were administered and ERPs recorded at the University of Greifswald (Greifswald, Germany) while performing the same imagery task. RESULTS: Reduced positive amplitude of a centroparietal startle-evoked ERP (156-352 ms after onset) significantly predicted higher questionnaire scores of anxiety/depression, reports of increased life dysfunction, greater comorbidity, and clinician ratings of heightened severity and poorer prognosis. The effect was general across principal diagnoses, found for both the Florida and German samples, and consistent in pattern despite differences in the tasks administered. CONCLUSIONS: The startle-evoked ERP reliably predicts severity and breadth of psychopathology, independent of task context. It is a potential significant contributor to a needed array of biological measures that might improve classification of anxiety and mood disorders.

17.
Artigo em Inglês | MEDLINE | ID: mdl-29795418

RESUMO

Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 107/kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add-back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five-year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution.

18.
Psychophysiology ; 55(10): e13197, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29732578

RESUMO

Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta-analysis of repetition effects for visual stimuli (Kim, 2017) reported cross-stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes.

19.
Behav Res Ther ; 104: 62-68, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29549752

RESUMO

Although avoidance and escape behaviors each contribute to maintaining anxiety disorders, only avoidance completely eliminates exposure to the aversive context. Current research compared anticipatory defensive engagement when aversion could either be completely avoided or escaped after initial exposure; in addition, this research examined the impact of trait anxiety on coping-related defensive engagement. Cues signaled that upcoming rapid action would avoid (block), escape (terminate), or not affect subsequent aversive exposure; the acoustic startle reflex was measured during each anticipatory interval to index defensive engagement, and blink magnitudes were compared across low-, moderate-, and high-anxious individuals. For all participants, startle was potentiated when aversive exposure was uncontrollable and attenuated when aversion was avoidable. On escape trials, on the other hand, startle potentiation increased with rising participant anxiety. Results suggest 1) defensive engagement is generally reduced in avoidance contexts relative to contexts in which exposure is certain, and; 2) trait anxiety increases defensive engagement specifically when aversive exposure can be controlled but remains certain.

20.
Pediatr Blood Cancer ; 65(6): e27003, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29512859

RESUMO

Vinblastine and targeted therapies induce remissions in patients with relapsed or progressive anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL). Central nervous system (CNS) prophylaxis often is not included during re-induction in CNS-negative relapse patients. We report on five patients with progressive or early relapsed ALK-positive ALCL who developed CNS progression during re-induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation. These observations suggest that CNS prophylaxis should be considered in ALCL patients suffering progression during initial therapy who receive re-induction using agents with limited CNS penetration.

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