Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia: the PETHEMA-PALG experience.

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.

The Development of Cortical Responses to the Integration of Audiovisual Speech in Infancy.

In adults, the integration of audiovisual speech elicits specific higher (super-additive) or lower (sub-additive) cortical responses when compared to the responses to unisensory stimuli. Although there is evidence that the fronto-temporal network is active during perception of audiovisual speech in infancy, the development of fronto-temporal responses to audiovisual integration remains unknown. In the current study, 5-month-olds and 10-month-olds watched bimodal (audiovisual) and alternating unimodal (auditory + visual) syllables. In this context we use alternating unimodal to denote alternating auditory and visual syllables that are perceived as separate syllables by adults. Using fNIRS we measured responses over large cortical areas including the inferior frontal and superior temporal regions. We identified channels showing different responses to bimodal than alternating unimodal condition and used multivariate pattern analysis (MVPA) to decode patterns of cortical responses to bimodal (audiovisual) and alternating unimodal (auditory + visual) speech. Results showed that in both age groups integration elicits cortical responses consistent with both super- and sub-additive responses in the fronto-temporal cortex. The univariate analyses revealed that between 5 and 10 months spatial distribution of these responses becomes increasingly focal. MVPA correctly classified responses at 5 months, with key input from channels located in the inferior frontal and superior temporal channels of the right hemisphere. However, MVPA classification was not successful at 10 months, suggesting a potential cortical re-organisation of audiovisual speech perception at this age. These results show the complex and non-gradual development of the cortical responses to integration of congruent audiovisual speech in infancy.

Theory of Mind and Parental Mental-State Talk in Children with CIs.

Previous studies have suggested that parents may support the development of theory of mind (ToM) in their child by talking about mental states (mental state talk; MST). However, MST has not been sufficiently explored in deaf children with cochlear implants (CIs). This study investigated ToM and availability of parental MST in deaf children with CIs (n = 39, Mage = 62.92, SD = 15.23) in comparison with their peers with typical hearing (TH; n = 52, Mage = 52.48, SD = 1.07). MST was measured during shared storybook reading. Parents' narratives were coded for cognitive, emotional, literal, and non-mental references. ToM was measured with a parental questionnaire. Children with CIs had lower ToM scores than their peers with TH, and their parents used more literal references during shared storybook reading. There were no significant differences in the frequencies of cognitive and emotional references between groups. Parental emotional references contributed positively to children's ToM scores when controlling for the child's age and receptive grammar only in the CI group. These results indicated some distinctive features in parents of deaf children with CIs' MST and highlighted the role of MST in the development of ToM abilities in this group.

False Belief Understanding in Deaf Children With Cochlear Implants.

Theory of mind (ToM) is crucial for social interactions. Previous research has indicated that deaf and hard-of-hearing children born into hearing families (DoH) are at risk of delayed ToM development. However, it is unclear whether this is the case for DoH children who receive cochlear implants (CIs) before and around the second year of life. The present study aimed to investigate false belief understanding (FBU) in DoH children with CIs. The relationships between false belief task (FBT) performance, sentence comprehension, age at implantation, duration of CI use, and Speech Recognition Threshold were explored. A total of 94 children with typical levels of hearing (TH) and 45 DoH children (age range: 3-8), who received their first CI between 6 and 27 months of age, were tested on the FBT and a sentence comprehension test. Results showed that 4- and 5-year-old children with CIs performed significantly worse than their peers with TH on the FBT; 6- to 8-year-old children with CIs performed similarly to age-matched children with TH. Age at implantation and duration of CI use were correlated with sentence comprehension but not with the FBT. The results indicated that FBU was delayed until the age of 6 years in most of children with CIs.

Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial.

BACKGROUND: Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. METHODS: The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1-4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. FINDINGS: Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3-35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7-33·8] vs 21·3 months [18·0-24·7]; hazard ratio 0·72, 95% CI 0·58-0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. INTERPRETATION: Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. FUNDING: Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.

miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 expressions in autologous hematopoietic stem cell transplantation and their impact on engraftment.

OBJECTIVE: MicroRNAs engaged in angiogenesis and hematopoiesis can influence hematopoietic stem cells (HSCs) homing after transplantation by targeting bone marrow niche microenvironment. This study aimed to examine the kinetics of miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 in autologous HSC transplantation settings. METHODS: The study comprised of 51 patients with hematological malignancies (42 multiple myeloma, 9 lymphoma). Samples were taken at four time points: before conditioning, after chemotherapy but prior to autologous HSC transplantation (day 0), on day +7, and +14 days after HSCT. The miRNA levels were evaluated by the real-time PCR method. RESULTS: A significant, steady decline of all tested microRNAs in the course of transplantation, as compared to the baseline, was found. The study revealed that higher levels of miRNA-15a, miRNA-16, miRNA-126, and miRNA-146a on day 0 correlated with longer time to engraftment. Additionally, a positive correlation between the levels of miRNA-15a, miRNA-146a, and miRNA-223 assessed on day +7 and the time to engraftment was observed. CONCLUSIONS: In conclusion, all investigated microRNAs changed significantly in the course of transplantation. Our results suggest that the miRNAs may participate in hematopoietic recovery in the early post-transplant period and influence engraftment efficiency after HSCT.

Affective and Cognitive Verbal Theory of Mind in Schizophrenia: Results From a Novel Paradigm.

OBJECTIVES: Impairments of Theory of Mind (ToM) have been repeatedly demonstrated in patients with schizophrenia (SCZ). However, only a handful of studies have explored deficits in affective and cognitive subcomponents of ToM. Thus, this study aims to examine affective and cognitive ToM abilities in SCZ by using a novel, verbal paradigm. METHODS: Twenty-four SCZ and 22 healthy comparison subjects (HC) completed a battery of tasks, which consisted of: (i) Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), (ii) three well-established tasks measuring social cognitive abilities, and (iii) original tasks which assess ability to infer cognitive and affective mental states based on everyday verbal social interactions. RESULTS: In line with previous findings, SCZ were outperformed by HC in all tasks. However, the interaction effect of the group and the task showed that cognitive (as opposed to affective) ToM was more profoundly impaired in patients with SCZ. CONCLUSIONS: It is proposed that in SCZ group cognitive ToM is more impaired as it involves more effortful reflective processes, while affective ToM, which is more automatic and based on reflexive processes, may differentiate patients from healthy comparison subjects to a lesser extent. (JINS, 2018, 24, 305-309).

SMAC protein expression as a potent favorable prognostic factor in locally advanced breast cancer.

Preoperative systemic therapy including neoadjuvant chemotherapy (NCT) is standard treatment in locally advanced breast cancer (LABC), the aim of which is to enable a radical surgery and to reduce the risk of local and distant recurrence. It has been established that NCT in LABC may effectively induce apoptosis. The study objective was to assess the role of a proapoptotic second mitochondria-derived activator of apoptosis (SMAC) in LABC. The study group comprised 56 patients with advanced non-metastatic breast cancer (stage IIB -node positive and III), who received NCT followed by surgery and adjuvant treatment. Expression of SMAC protein was analysed using the immunohistochemistry technique in core biopsies sampled from the patients' breasts before NCT and in surgical specimens collected after completion of NCT. Expression of SMAC was significantly higher in the breast cancer specimens after NCT (p < 0.01). High expression of SMAC in the core biopsy before NCT correlated with a pathological complete remission (pCR, p < 0.01). The patients with a high expression of SMAC in the surgical specimens after NCT had longer DFS. Our study proves a potential role of SMAC expression in LABC as a novel favourable prognostic factor in LABC for pCR and disease-free survival (DFS).

VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment.

As a site of complicated interactions among cytokines, bone marrow niche has been the subject of many scientific studies, mainly in the context of the proteins influencing damage or recovery of endothelium after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we aimed at exploring mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. The aim of our study was to evaluate levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous HSCT and to examine their influence on hematological recovery. Forty-three patients with hematological malignancies (33 multiple myeloma, 10 lymphoma) were enrolled in the study. Plasma samples were taken at five time points: before conditioning treatment (BC), on transplantation day (0) and 7 (+7), 14 (+14), and 21 (+21) days after HSCT. The cytokine levels were evaluated by ELISA method. Our study revealed decreased levels of VEGF, ANGPT1, and MMP-9 in the early post-transplant period as compared to the baseline (BC). ANGPT2 was decreased after conditioning treatment, but tended to increase from day +7. On day +7, positive correlations between ANGPT1 level as well as MMP-9 and the time to engraftment were observed. As opposite to ANGPT1, negative correlation between ANGPT2 level on day +7 after HSCT and the time to hematological recovery was noticed. Our study suggests that investigated cytokines are an important part of bone marrow environment and significantly influence the time to engraftment after HSCT.

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial.

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.

Influence of Acoustic Overstimulation on the Central Auditory System: An Functional Magnetic Resonance Imaging (fMRI) Study.

BACKGROUND The goal of the fMRI experiment was to explore the involvement of central auditory structures in pathomechanisms of a behaviorally manifested auditory temporary threshold shift in humans. MATERIAL AND METHODS The material included 18 healthy volunteers with normal hearing. Subjects in the exposure group were presented with 15 min of binaural acoustic overstimulation of narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1 session before and 3 sessions after acoustic overstimulation and involved 3.5-4.5 kHz sweeps. RESULTS The outcomes of the study indicate a possible effect of acoustic overstimulation on central processing, with decreased brain responses to auditory stimulation up to 20 min after exposure to noise. The effect can be seen already in the primary auditory cortex. Decreased BOLD signal change can be due to increased excitation thresholds and/or increased spontaneous activity of auditory neurons throughout the auditory system. CONCLUSIONS The trial shows that fMRI can be a valuable tool in acoustic overstimulation studies but has to be used with caution and considered complimentary to audiological measures. Further methodological improvements are needed to distinguish the effects of TTS and neuronal habituation to repetitive stimulation.

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo-HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: a retrospective, multicenter Polish Adult Leukemia Group study.

The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.

The kinetics of hematopoietic niche cytokines and their influence on mobilization efficacy and timing in patients with hematological malignancies.

The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM-1, VEGF, MMP-9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years. The group consisted of patients with multiple myeloma (26) and lymphoma (8). The mobilization procedures comprised chemotherapy and then G-CSF. Blood samples were collected before chemotherapy (N = 34) and on the day of the first apheresis (N = 26). Cytokines were evaluated with ELISA assay. We observed significant increase in VCAM-1 levels during mobilization. On contrary, VEGF and SDF levels decreased during mobilization procedure. The levels of MMP-9 were stable during mobilization. We divided patients according to baseline cytokines levels below and above median into "low" and "high" expressors. The group of VEGF "low" expressors had longer median time of G-CSF treatment before first apheresis than 'high' expressors. Baseline VEGF levels correlated adversely with duration of G-CSF treatment before first apheresis. Patients were also divided according to median cytokines levels at apheresis into "low" and "high" expressors. "High" VCAM-1 expressors had higher CD34+in peripheral blood as well as higher CD34+numbers collected during first apheresis than "low" expressors. In conclusion, the levels of niche cytokines change significantly during mobilization in patients with hematopoietic malignancies. Baseline VEGF can influence timing of mobilization. Higher VCAM-1 corresponds with higher mobilization efficacy.

The fructose tolerance test in patients with chronic kidney disease and metabolic syndrome in comparison to healthy controls.

BACKGROUND: Fructose acutely raises serum uric acid in normal subjects, but the effect in subjects with metabolic syndrome or subjects with chronic kidney disease is unknown. The aim of the study was to evaluate changes in serum uric acid during the fructose tolerance test in patients with chronic kidney disease, metabolic syndrome with comparison to healthy controls. METHODS: Studies were performed in 36 subjects with obesity (body mass index >30) and metabolic syndrome, 14 patients with stage 3 chronic kidney disease, and 25 healthy volunteers. The fructose tolerance test was performed in each patient. The change in serum uric acid during the fructose challenge was correlated with baseline ambulatory blood pressure, serum uric acid, metabolic, and inflammatory markers, and target organ injury including carotid intima media thickness and renal resistive index (determined by Doppler). RESULTS: Absolute serum uric acid values were highest in the chronic kidney disease group, followed by the metabolic syndrome and then healthy controls. Similar increases in serum uric acid in response to the fructose tolerance test was observed in all three groups, but the greatest percent rise was observed in healthy controls compared to the other two groups. No significant association was shown between the relative rise in uric acid and clinical or inflammatory parameters associated with kidney disease (albuminuria, eGFR) or metabolic syndrome. CONCLUSIONS: Subjects with chronic kidney disease and metabolic syndrome have higher absolute uric acid values following a fructose tolerance test, but show a relatively smaller percent increase in serum uric acid. Changes in serum uric acid during the fructose tolerance test did not correlate with changes in metabolic parameters, inflammatory mediators or with target organ injury. These studies suggest that acute changes in serum uric acid in response to fructose do not predict the metabolic phenotype or presence of inflammatory mediators in subjects with obesity, metabolic syndrome or chronic kidney disease. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526.

Left ventricular remodeling and arterial remodeling in patients with chronic kidney disease stage 1-3.

INTRODUCTION: Chronic kidney disease (CKD) is an independent factor for cardiovascular system complications, such as arterial hypertension, left ventricular hypertrophy (LVH), heart failure or accelerated atherosclerosis progression. The aim of the paper was to analyze left ventricular and arterial remodeling in patients with CKD stages 1-3 to identify the subclinical marker of cardiovascular system damage which changes first in the course of CKD. METHODS: The examined group consisted of 90 patients with CKD stage 1-3 and 30 subjects constituting the control group. Left ventricular mass index (LVMI), left ventricular relative wall thickness (RWT) and ejection fraction (EF) were determined by echocardiographic examination. Pulse wave velocity (PWV) between the carotid and femoral arteries as well as common carotid artery intima-media thickness (IMT) was measured. 24-h ambulatory blood pressure monitoring was performed in all subjects. RESULTS: No differences were found between blood pressure values in the examined groups of patients with CKD1, CKD2 and CKD3. Concentric remodeling was found in 20.0%, concentric hypertrophy in 22.2% and eccentric hypertrophy in 18.9% of patients. LVMI values in patients with CKD2 and 3 were higher than in the control group. IMT values in patients with CKD3 were higher than in patients with CKD2. PWV in patients with stage 3 CKD was significantly higher than in the control group (p < 0.05). CONCLUSIONS: In the course of CKD, the left ventricle undergoes remodeling earlier than large arterial vessels. Echocardiographic assessment of LVH in early stages of CKD may identify patients at increased cardiovascular risk.

[The possibilities and limitations of simultaneous EEG-fMRI registration--the alpha rhythm study]. / Mozliwosci i problemy jednoczesnych rejestracji EEG-fMRI--badanie rytmu alfa.

INTRODUCTION: Simultaneous EEG-fMRI registration is rapidly evolving and has received substantial attention. This technique provides precise information in both spatial and temporal domain. The biological basis of the EEG and fMRI signal is different which, on the one hand makes results interpretation more difficult but, on the other hand, gives more convincing arguments on the neural correlates of sensory and cognitive processes. In this paper we present an example of implementation of simultaneous EEG-fMRI registration for alpha rhythm source mapping. MATERIAL AND METHODS: 60 young males took part in this study. For the group analysis we selected 33 individuals to obtain homogenous group. Siemens Magnetom Trio 3T and 64-electrode SynAmp2 Neuroscan EEG system was applied. Participants took part in fMRI imaging which adapted arrest reaction study. RESULTS: Averaged spectra amplitude distribution of alpha rhythm (8-13Hz) showed high activation in the occipito-parietal region and smaller but noticeable activity in the frontal area. FMRI results revealed activity in bilateral occipital lobe. Additional regions included the posterior cingulate gyrus, middle and superior frontal gyrus. Statistically significant areas with BOLD signal decrease were located in the temporal lobe and anterior cingulate gyrus. CONCLUSION: The obtained results indicate overlapping regions of the presented EEG outcomes and fMRI maps for alpha rhythm study. Simultaneous EEG-fMRI technique allows for registration of spontaneous EEG activity with both high temporal and spatial resolution. The alpha rhythm might reflect the extensive brain process involving the thalamo-occipito-frontal connections.

Polymorphism of CD44 influences the efficacy of CD34(+) cells mobilization in patients with hematological malignancies.

In the last decade, peripheral blood was the main source of hematopoietic stem cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms of HSC mobilization are still not clear and the efficacy of the procedure is hardly predictable. Ligand-receptor interactions of adhesion molecules, such as SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of HSC in the hematopoietic niche. There is some evidence that disruption of the ligand-receptor complex leads to the egress of HSCs to the peripheral blood. The aim of the present study was the evaluation of constitutive polymorphism of genes encoding cytokines and receptors present in the HSC niche and their impact on the efficacy of mobilization of HSCs in patients with hematological malignancies. We enrolled 110 patients (60 females and 50 males) in the study. The median age of the patients was 55 (range, 22 to 69) years. The group consisted of patients with multiple myeloma (n = 74), non-Hodgkin lymphoma (n = 19), Hodgkin lymphoma (n = 15), or acute myeloid leukemia (n = 2). The mobilization procedures comprised chemotherapy and subsequent granulocyte-colony stimulating factor (G-CSF) at a dose of 10 µg/kg daily. The poor mobilizers group was defined according to Italian National Bone Marrow Transplant Registry criteria: patients with peak CD34(+) in the peripheral blood < 20/µL or total yield < 2 × 10(6) CD34(+) cells/kg body weight in maximum 3 aphereses. Genotyping was performed using standard PCR-based assays. The group of patients (N = 108) who achieved minimal threshold for collections (CD34(+) at least 10/µL) proceeded to apheresis. The median total yield of CD34(+) in this group was 5.6 × 10(6) cells/kg body weight, whereas the median number of cells collected during the first apheresis was 3.3 × 10(6) cells/kg body weight. Median number of days of G-CSF treatment before first apheresis was 10. Fifteen patients fulfilled the criteria for poor mobilizer. The group of poor mobilizers had higher frequency of TT genotype in rs13347 (CD44) gene (CC+ CT versus TT P = .047). Patients homozygous for T allele had a lower total yield of CD34(+) cells/kg body weight than the group with allele C (median, 3.7 × 10(6)/kg versus 5.8 × 10(6)/kg; P = .019) and a lower number of CD34(+) cells gathered during first apheresis (.95 × 10(6)/kg versus 3.3 × 10(6)/kg, P = .04). Multivariate logistic regression analysis revealed that the CD44 TT genotype was the only factor associated with 5-fold higher risk of poor mobilization (P = .037). Polymorphic variants of CXCR4 and VCAM-1 did not significantly influence the efficacy of HSCs mobilization in our group of patients. In conclusion, our results indicate that among investigated single nucleotide polymorphisms (SNPs), only CD44 rs13347 has an impact on the efficacy of HSCs mobilization in patients with hematologic malignancies. CD44 SNPs analysis may be helpful for predicting the poor mobilizers population who may benefit from newer modalities using adhesion molecules inhibitors.

Reduced resting-state brain activity in the default mode network in children with (central) auditory processing disorders.

BACKGROUND: In recent years, there has been a growing interest in Central Auditory Processing Disorder (C)APD. However, the neural correlates of (C)APD are poorly understood. Previous neuroimaging experiments have shown changes in the intrinsic activity of the brain in various cognitive deficits and brain disorders. The present study investigated the spontaneous brain activity in (C)APD subjects with resting-state fMRI (rs-fMRI). METHODS: Thirteen children diagnosed with (C)APD and fifteen age and gender-matched controls participated in a rs-fMRI study during which they were asked to relax keeping their eyes open. Two different techniques of the rs-fMRI data analysis were used: Regional Homogeneity (ReHo) and Independent Component Analysis (ICA), which approach is rare. RESULTS: Both methods of data analysis showed comparable results in the pattern of DMN activity within groups. Additionally, ReHo analysis revealed increased co-activation of the superior frontal gyrus, the posterior cingulate cortex/the precuneus in controls, compared to the (C)APD group. ICA yielded inconsistent results across groups. CONCLUSIONS: Our ReHo results suggest that (C)APD children seem to present reduced regional homogeneity in brain regions considered a part of the default mode network (DMN). These findings might contribute to a better understanding of neural mechanisms of (C)APD.

Factors associated with prolonged COVID-related PTSD-like symptoms among adults diagnosed with mild COVID-19 in Poland.

COVID-19 has been considered a possible cause of post-traumatic stress disorder (PTSD) or similar conditions. However, what specific disease symptoms may contribute most to prolonged PTSD-like symptoms in COVID-19 survivors is unclear. The study aimed to present the factor structure of COVID-19 symptoms and identify which symptoms of COVID-19 best explain the subsequent presence of PTSD-like symptoms in mild COVID-19 survivors. COVID-positive adults (n = 341) completed online self-report scales at the baseline assessment (T1) and after approximately 4 months (T2), including The Patient Health Questionnaire Anxiety-Depression Scale; The Scale of Psychosocial Experience Related to COVID-19, The Primary Care PTSD Screen for DSM-5; and self-designed questionnaires evaluating the severity of COVID-related medical and neurocognitive symptoms and pre-pandemic variables. Exploratory factor analysis revealed five factors of COVID-19 symptoms: flu-like, respiratory, cold, neurological, and neurocognitive. Hierarchical logistic regression showed that besides selected control variables (anxiety and depression, presence of PTSD-like symptoms, COVID-related stigma in T1), neurocognitive symptoms of COVID-19 in T1 but not other symptoms of the disease were a significant predictor of the presence of PTSD-like symptom in T2. Findings suggest a need for a comprehensive neurocognitive assessment of people diagnosed with COVID-19 and prompt interventions targeting the prevention of potential risks for long-term PTSD-like states at the community level.

The kinetics and apoptotic profile of circulating endothelial cells in autologous hematopoietic stem cell transplantation in patients with lymphoproliferative disorders.

In neoplastic disorders, endothelial cells take part in tumor progression and also influence the recovery of hematopoiesis after high-dose chemotherapy. Measurements of circulating endothelial cells (CEC), their subsets and kinetics were taken in patients with lymphoid malignancies (37 multiple myeloma, ten lymphoma) during autologous hematopoietic stem cell transplantation (HSCT). CEC were evaluated by four-color flow cytometry at different time points. Additionally levels of angiopoietins 1 and 2 were evaluated by ELISA assay. The baseline number of CECs and their subsets in patients were higher than in the control group. The median CEC number dropped significantly after transplantation (from 9.5/µL to 6.2/µL, p < 0.001). Apoptosis of CECs 24 h after chemotherapy was enhanced in comparison to baseline values (median apoptotic CEC number 4.15/µL vs 3.1/µL; p < 0,001). The time for neutrophil engraftment was shorter for patients with a low apoptotic CEC count at baseline as compared to those with a high apoptotic CEC count (median time to engraftment 13 vs. 16 days respectively, p = 0.04). We observed an adverse correlation of progenitor CEC numbers measured 1 h after transplantation with the time to neutrophil engraftment (r = -0.49, p = 0.008). We also found a negative correlation between the number of CECs originating from microvessels measured 1 h after transplantation, and the time to neutrophil engraftment (r = -0.39, p = 0.04). Baseline angiopoietins 1 and 2 concentration did not influence the post-transplant regeneration time. CEC numbers significantly change during autologous HSCT. Our results suggest that progenitor CECs and CECs derived from microvessels both take part in successful engraftment.