Low-Cost EEG Multi-Subject Recording Platform for the Assessment of Students' Attention and the Estimation of Academic Performance in Secondary School.

The level of student attention in class greatly affects their academic performance. Teachers typically rely on visual inspection to react to students' attention in time, but this subjective method leads to inconsistencies across classes. Online education exacerbates the issue as students can turn off cameras and microphones to keep their own privacy. To address this, we present a novel, low-cost EEG-based platform for assessing students' attention and estimating their academic performance. In a study involving 34 secondary school students (aged 14 to 16), participants watched an academic video and answered evaluation questions while their EEG activity was recorded using a commercial headset. The results demonstrate a significant correlation (0.53, p-value = 0.003) between the power spectral density (PSD) of the EEG beta band (12-30 Hz) and students' academic performance. Additionally, there was a notable difference in PSD-beta between high and low academic performers. These findings encourage the use of PSD-beta for the immediate and objective assessment of both the student attention and the subsequent academic performance. The platform offers valuable and objective feedback to teachers, enhancing the effectiveness of both face-to-face and online teaching and learning environments.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

Impact of pre- and/or post-autologous stem cell transplantation exposure to brentuximab vedotin on survival outcomes in patients with high-risk Hodgkin lymphoma.

The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.

[Validity and reliability of the 8-item EUROHIS-QOL to assess Brazilian adults' quality of life]. / Validade e confiabilidade do EUROHIS-QOL 8-item para avaliar a qualidade de vida em adultos brasileiros.

The study evaluated the psychometric properties of the EUROHIS-QOL 8-item scale in Brazilian adults. The EUROHIS-QOL is a measurement of quality of life developed based on the generic instruments of WHOQOL-100 and WHOQOL-BREF. Based on data from a prospective cohort of 1,100 adults, participants in the baseline in 2006 and 2007, exploratory factor analysis, internal consistency, reliability, and discriminant validity were performed via multitrait-multimethod analysis, with the calculation of the average variance extracted (AVE). Confirmatory factor analysis was conducted with 573 of these participants in 2013 to 2018. Solutions were tested with one and with two factors named functional capacity and socioeconomic conditions. Both solutions presented good internal consistency and reliability. The correlation between the items was 0.535, and the AVE was 0.397 for solution with one factor, and 0.528 and 0.341 for factors one and two, respectively, indicating good discriminant validity in the bifactorial solution. Both factors had eigenvalues greater than one and factor loadings ranging from 0.398 to 0.915. The adjustment of the unifactorial solution presented: χ2 = 186 (g.l. = 18), p < 0.001, RMSEA = 0.128 (90%CI: 0.111-0.145), CFI = 0.960, TLI = 0.938, and SMRM = 0.042; while in the bifactorial presented: χ2 = 135 (g.l. = 17), p < 0.001, RMSEA = 0.110 (90%CI: 0.093-0.128), CFI = 0.972, TLI = 0.954, and SMRM = 0.035. Overall, the results provide reasonable evidence for the construct validity and reliability of the EUROHIS-QOL 8-item. Instruments with fewer items, as in our case, provide greater practicality and are ideal for use in population-based studies with extensive samples.

O estudo avaliou as propriedades psicométricas da escala EUROHIS-QOL 8-item em adultos brasileiros. O EUROHIS-QOL 8-item é uma medida de qualidade de vida desenvolvida a partir dos instrumentos genéricos WHOQOL-100 e WHOQOL-BREF. A partir dos dados de uma coorte prospectiva com 1.100 adultos participantes da linha de base em 2006 e 2007, foram realizadas análise fatorial exploratória, consistência interna, confiabilidade e validade discriminante por meio da análise multitraço-multimétodo, com o cálculo das variâncias médias extraídas (AVE). A análise fatorial confirmatória foi conduzida com 573 desses participantes nos anos de 2013 a 2018. Foram testadas soluções com um e com dois fatores nomeados capacidade funcional e condições socioeconômicas. Ambas as soluções apresentaram boa consistência interna e confiabilidade. A correlação entre os itens foi de 0,535 e as AVE foram 0,397 para solução com um fator, e 0,528 e 0,341 para os fatores um e dois, respectivamente, indicando boa validade discriminante na solução bifatorial. Os dois fatores tiveram autovalores maiores que um e cargas fatoriais variando de 0,398 a 0,915. O ajustamento da solução unifatorial foi: χ2 = 186 (g.l. = 18), p < 0,001, RMSEA = 0,128 (IC90%: 0,111-0,145), CFI = 0,960, TLI = 0,938 e SMRM = 0,042; enquanto na bifatorial era: χ2 = 135 (g.l. = 17), p < 0,001, RMSEA = 0,110 (IC90%: 0,093-0,128), CFI = 0,972, TLI = 0,954 e SMRM = 0,035. De modo geral, os resultados fornecem evidências razoáveis da validade de construto e confiabilidade do EUROHIS-QOL 8-item. Instrumentos com menor número de itens, como é o caso, proporcionam maior praticidade e são ideais para utilização em estudos de base populacional com uso de amostras extensas.

El estudio evaluó las propiedades psicométricas de la escala EUROHIS-QOL 8-ítems (Europe Health Interview Surveys Quality of Life Abbreviated Instrument) en adultos brasileños. El índice de 8 ítems EUROHIS-QOL es una medida de calidad de vida desarrollada con base en los instrumentos genéricos WHOQOL-100 (World Health Organization Quality of Life Instrument) y WHOQOL-BREF (World Health Organization Quality of Life Abbreviated Instrument). Con base en los datos de una cohorte prospectiva de 1.100 adultos que participaron en la línea de base en 2006 y 2007, se realizaron los análisis factorial exploratorio, de consistencia interna, de confiabilidad y de validez discriminante mediante un análisis multirrasgo-multimétodo, con el cálculo de la varianza media extraída (AVE). Se realizó un análisis factorial confirmatorio con 573 de estos participantes de 2013 hasta 2018. Se probaron soluciones de uno y dos factores denominados capacidad funcional y condiciones socioeconómicas. Ambas soluciones presentaron buena consistencia interna y confiabilidad. La correlación entre los ítems fue de 0,535 y las AVE fueron de 0,397 para la solución de un factor y de 0,528 y 0,341 para los factores uno y dos, respectivamente, lo que indica una buena validez discriminante en la solución bifactorial. Los dos factores tuvieron autovalores mayores a uno y cargas factoriales que oscilaron entre 0,398 y 0,915. El ajuste de la solución unifactorial fue: χ2 = 186 (g.l. = 18), p < 0,001, RMSEA = 0,128 (IC90%: 0,111-0,145), CFI = 0,960, TLI = 0,938 y SMRM = 0,042; mientras que en la bifactorial fue: χ2 = 135 (g.l. = 17), p < 0,001, RMSEA = 0,110 (IC90%: 0,093-0,128), CFI = 0,972, TLI = 0,954 e SMRM = 0,035. En general, los resultados proporcionan evidencias razonables de la validez de constructo y confiabilidad del EUROHIS-QOL 8-ítems. Los instrumentos con menor número de ítems, como es el caso, proporcionan mayor practicidad y son ideales para su uso en estudios de base poblacional con muestras amplias.

Panel Sequencing for Clinically Oriented Variant Screening and Copy Number Detection in Chronic Lymphocytic Leukemia Patients.

According to current guidelines, in chronic lymphocytic leukemia (CLL), only the TP53 molecular status must be evaluated prior to every treatment's initiation. However, additional heterogeneous genetic events are known to confer a proliferative advantage to the tumor clone and are associated with progression and treatment failure in CLL patients. Here, we describe the implementation of a comprehensive targeted sequencing solution that is suitable for routine clinical practice and allows for the detection of the most common somatic single-nucleotide and copy number variants in genes relevant to CLL. We demonstrate that this cost-effective strategy achieves variant detection with high accuracy, specificity, and sensitivity. Furthermore, we identify somatic variants and copy number variations in genes with prognostic and/or predictive value, according to the most recent literature, and the tool provides evidence about subclonal events. This next-generation sequencing (NGS) capture-based target assay is an improvement on current approaches in defining molecular prognostic and/or predictive variables in CLL patients.

Validade e confiabilidade do EUROHIS-QOL 8-item para avaliar a qualidade de vida em adultos brasileiros / Validity and reliability of the 8-item EUROHIS-QOL to assess Brazilian adults' quality of life / Validez y confiabilidad de EUROHIS-QOL-8-ítem para evaluar la calidad de vida en adultos brasileños

O estudo avaliou as propriedades psicométricas da escala EUROHIS-QOL 8-item em adultos brasileiros. O EUROHIS-QOL 8-item é uma medida de qualidade de vida desenvolvida a partir dos instrumentos genéricos WHOQOL-100 e WHOQOL-BREF. A partir dos dados de uma coorte prospectiva com 1.100 adultos participantes da linha de base em 2006 e 2007, foram realizadas análise fatorial exploratória, consistência interna, confiabilidade e validade discriminante por meio da análise multitraço-multimétodo, com o cálculo das variâncias médias extraídas (AVE). A análise fatorial confirmatória foi conduzida com 573 desses participantes nos anos de 2013 a 2018. Foram testadas soluções com um e com dois fatores nomeados capacidade funcional e condições socioeconômicas. Ambas as soluções apresentaram boa consistência interna e confiabilidade. A correlação entre os itens foi de 0,535 e as AVE foram 0,397 para solução com um fator, e 0,528 e 0,341 para os fatores um e dois, respectivamente, indicando boa validade discriminante na solução bifatorial. Os dois fatores tiveram autovalores maiores que um e cargas fatoriais variando de 0,398 a 0,915. O ajustamento da solução unifatorial foi: χ2 = 186 (g.l. = 18), p < 0,001, RMSEA = 0,128 (IC90%: 0,111-0,145), CFI = 0,960, TLI = 0,938 e SMRM = 0,042; enquanto na bifatorial era: χ2 = 135 (g.l. = 17), p < 0,001, RMSEA = 0,110 (IC90%: 0,093-0,128), CFI = 0,972, TLI = 0,954 e SMRM = 0,035. De modo geral, os resultados fornecem evidências razoáveis da validade de construto e confiabilidade do EUROHIS-QOL 8-item. Instrumentos com menor número de itens, como é o caso, proporcionam maior praticidade e são ideais para utilização em estudos de base populacional com uso de amostras extensas.

The study evaluated the psychometric properties of the EUROHIS-QOL 8-item scale in Brazilian adults. The EUROHIS-QOL is a measurement of quality of life developed based on the generic instruments of WHOQOL-100 and WHOQOL-BREF. Based on data from a prospective cohort of 1,100 adults, participants in the baseline in 2006 and 2007, exploratory factor analysis, internal consistency, reliability, and discriminant validity were performed via multitrait-multimethod analysis, with the calculation of the average variance extracted (AVE). Confirmatory factor analysis was conducted with 573 of these participants in 2013 to 2018. Solutions were tested with one and with two factors named functional capacity and socioeconomic conditions. Both solutions presented good internal consistency and reliability. The correlation between the items was 0.535, and the AVE was 0.397 for solution with one factor, and 0.528 and 0.341 for factors one and two, respectively, indicating good discriminant validity in the bifactorial solution. Both factors had eigenvalues greater than one and factor loadings ranging from 0.398 to 0.915. The adjustment of the unifactorial solution presented: χ2 = 186 (g.l. = 18), p < 0.001, RMSEA = 0.128 (90%CI: 0.111-0.145), CFI = 0.960, TLI = 0.938, and SMRM = 0.042; while in the bifactorial presented: χ2 = 135 (g.l. = 17), p < 0.001, RMSEA = 0.110 (90%CI: 0.093-0.128), CFI = 0.972, TLI = 0.954, and SMRM = 0.035. Overall, the results provide reasonable evidence for the construct validity and reliability of the EUROHIS-QOL 8-item. Instruments with fewer items, as in our case, provide greater practicality and are ideal for use in population-based studies with extensive samples.

El estudio evaluó las propiedades psicométricas de la escala EUROHIS-QOL 8-ítems (Europe Health Interview Surveys Quality of Life Abbreviated Instrument) en adultos brasileños. El índice de 8 ítems EUROHIS-QOL es una medida de calidad de vida desarrollada con base en los instrumentos genéricos WHOQOL-100 (World Health Organization Quality of Life Instrument) y WHOQOL-BREF (World Health Organization Quality of Life Abbreviated Instrument). Con base en los datos de una cohorte prospectiva de 1.100 adultos que participaron en la línea de base en 2006 y 2007, se realizaron los análisis factorial exploratorio, de consistencia interna, de confiabilidad y de validez discriminante mediante un análisis multirrasgo-multimétodo, con el cálculo de la varianza media extraída (AVE). Se realizó un análisis factorial confirmatorio con 573 de estos participantes de 2013 hasta 2018. Se probaron soluciones de uno y dos factores denominados capacidad funcional y condiciones socioeconómicas. Ambas soluciones presentaron buena consistencia interna y confiabilidad. La correlación entre los ítems fue de 0,535 y las AVE fueron de 0,397 para la solución de un factor y de 0,528 y 0,341 para los factores uno y dos, respectivamente, lo que indica una buena validez discriminante en la solución bifactorial. Los dos factores tuvieron autovalores mayores a uno y cargas factoriales que oscilaron entre 0,398 y 0,915. El ajuste de la solución unifactorial fue: χ2 = 186 (g.l. = 18), p < 0,001, RMSEA = 0,128 (IC90%: 0,111-0,145), CFI = 0,960, TLI = 0,938 y SMRM = 0,042; mientras que en la bifactorial fue: χ2 = 135 (g.l. = 17), p < 0,001, RMSEA = 0,110 (IC90%: 0,093-0,128), CFI = 0,972, TLI = 0,954 e SMRM = 0,035. En general, los resultados proporcionan evidencias razonables de la validez de constructo y confiabilidad del EUROHIS-QOL 8-ítems. Los instrumentos con menor número de ítems, como es el caso, proporcionan mayor practicidad y son ideales para su uso en estudios de base poblacional con muestras amplias.

Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study.

BACKGROUND: Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). METHODS: Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. RESULTS: Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. CONCLUSION: A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

Addition of chemotherapy to nivolumab after PD-1 inhibitor failure as bridge to allogeneic stem cell transplantation in classical Hodgkin's lymphoma: report on three cases and literature review.

The poor prognosis of refractory or relapsed (R/R) classical Hodgkin's lymphoma (cHL) after autologous stem cell transplantation has improved greatly due to the introduction of brentuximab vedotin and PD-1 inhibitors. However, the duration of response achieved with these novel agents is too short. The information about the management of patients after anti-PD-1 therapy failure is very limited in cHL, although chemotherapy alone or combined with PD-1 inhibitors has shown encouraging results. We report three cases of heavily pretreated cHL, refractory to nivolumab monotherapy, successfully rescued with the addition of chemotherapy to nivolumab, as a bridge to allogeneic stem cell transplantation (allo-SCT). All three patients presented poor clinical features such as three to four previous lines including brentuximab vedotin and autologous stem cell transplantation, refractoriness to the last line of therapy previous to nivolumab, and rapid disease progression. Notwithstanding these characteristics and nivolumab failure, they achieved a complete response after the addition of chemotherapy, were consolidated with allo-SCT, and still remain in complete response. There are few studies concerning the combination of PD-1 inhibitors and chemotherapy after nivolumab failure, including one retrospective study and one phase II trial with nivolumab plus bendamustine. Therefore, only few patients are consolidated with allo-SCT. However, there are several ongoing trials investigating new combinations of chemotherapy and PD-1 inhibitors in R/R cHL, as well as in first line. All these data suggest that anti-PD-1 therapy may reprogram the immune system, activating and inhibiting effector and immunosuppressive cells, respectively, leading to overtake of chemorefractoriness. Allo-SCT can increase the immune-related events of patients treated with anti-PD-1 previously, consistent on acute graft-versus-host disease, sinusoidal obstruction syndrome, and noninfectious febrile syndrome. In conclusion, the combination of PD-1 inhibitor and chemotherapy may be a feasible therapy after anti-PD-1 treatment failure as a bridge to allo-SCT.

Central Nervous System Involvement in Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders after Allogeneic Hematopoietic Stem Cell Transplantation.

Central nervous system (CNS) involvement in Epstein-Barr virus-related post-transplant lymphoproliferative disorders (EBV-PTLDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poorly defined. We analyzed the incidence, clinical and pathological characteristics, and impact on outcomes of EBV-PTLDs with CNS involvement (CNS-PTLDs) in 1009 consecutive adult patients undergoing allo-HSCT at a single-center institution. Four hundred eighty-two patients received matched sibling donor (MSD) transplants, 388 umbilical cord blood transplants (UCBTs), 56 matched unrelated donor (MUD) transplants, and 83 haploidentical transplants. We detected 25 cases of biopsy-proven EBV-PTLDs. Of these, nine patients (36%) had CNS-PTLDs: six after UCBT (67%), one after MSD transplantation (11%), one after MUD transplantation (11%), and one after haploidentical transplantation (11%). The 5-year cumulative incidence risk of CNS-PTLDs was 0.9%. Median time from transplant to CNS-PTLDs was 187 days, and all patients had neurological symptoms at diagnosis. Six out of the nine cases (67%) occurred with systemic involvement, and three cases (33%) had isolated CNS involvement. The most frequent histological subtype was monomorphic EBV-PTLD, and laboratory characteristics were similar to EBV-PTLDs without CNS involvement. We observed statistical differences in the rate of positive EBV DNA detection in plasma between isolated CNS-PTLDs (detection in one out of three, 33%) and the rest of the EBV-PTLDs (100%) (P = .01). Treatment strategies included chemotherapy, radiotherapy, and T cell therapy. However, seven out of nine patients died due to progression of the CNS-PTLDs at a median time of 17 days (range, 8 to 163) from diagnosis. The 5-years overall survival in patients who developed CNS-PTLDs was 22% (95% confidence interval [CI], 7% to 75%) and 5-year treatment-related mortality was 78% (95% CI, 51% to 100%), with no statistically significant differences between CNS-PTLDs and the rest of the EBV-PTLDs. In conclusion, despite advances in EBV monitoring and treatment strategies, CNS-PTLDs remain an uncommon but serious complication after allo-HSCT, with very poor prognosis.

A cross-cultural comparison of visual search strategies and response times in road hazard perception testing.

Road hazard perception is considered the most prominent higher-order cognitive skill related to traffic-accident involvement. Regional cultures and social rules that govern acceptable behavior may influence drivers' interpretation of a traffic situation and, consequently, the correct identification of potentially hazardous situations. Here, we aimed to compare hazard perception skills among four European countries that differ in their traffic culture, policies to reduce traffic risks, and fatal crashes: Ukraine, Italy, Spain, and Sweden. We developed a static hazard perception test in which driving scenes with different levels of braking affordance were presented while drivers' gaze was recorded. The test required drivers to indicate the action they would undertake: to brake vs. to keep driving. We assessed 218 young adult drivers. Multilevel models revealed that the scenes' levels of braking affordance (i.e., road hazard) modulated drivers' behavior. As the levels of braking affordance increased, drivers' responses became faster and their gaze entropy decreased (i.e., visual search strategy became less erratic). The country of origin influenced these effects. Ukrainian drivers were the fastest and Swedish drivers were the slowest to respond. For all countries, the decrement in response times was less marked in the case of experienced drivers. Also, Spanish drivers showed the most structured (least erratic) visual search strategy, whereas the Italians had the most rigid (most constant) one. These results suggest that road hazard perception can be defined cross-culturally, with cultural factors (e.g., traffic climate, legislation) modulating response times and visual search strategies. Our results also support the idea that a multimodal assessment methodology is possible for mass testing of road hazard perception and its outcomes would be relevant to understand how different traffic cultures shape driving behavior.

Potential Survival Benefit for Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation after Nivolumab Therapy for Relapse/Refractory Hodgkin Lymphoma: Real-Life Experience in Spain.

Clinical trials have shown that nivolumab has remarkable activity against relapsed/refractory classical Hodgkin lymphoma (cHL). However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation therapy in these patients remains controversial. We performed a retrospective analysis of data from 74 patients treated with nivolumab. The overall response rate was 58% (including 30.6% with complete responses). Treatment-related adverse events were reported in 56.8% of patients (grade ≥3 in 9.4%). The main reasons for nivolumab discontinuation were referral for transplantation (41.7% patients) and disease progression (37.5%). The 2-year overall survival (OS) rate was 52% for the entire series. Ultimately, 39 patients underwent allo-HSCT. The cumulative incidence of grade II-IV acute graft-versus-host disease was 33.3% (grade III-IV in 2 patients). The cumulative incidence of nonrelapse mortality was 13.2%. Among the patients who responded to nivolumab, the 2-year OS and progression-free survival (PFS) were higher in patients who underwent consolidation with allo-HSCT (77.5% versus 42.6% [P = .126] and 73.9% versus 27.2% [P = .025], respectively). Thus, the efficacy and safety of nivolumab were comparable to values reported in previous clinical trials. The percentage of patients who bridged to transplantation was high, indicating a preference for Spanish physicians. These results suggest that consolidation allo-HSCT increases OS and PFS.

Demyelination-Remyelination of the Rat Caudal Cerebellar Peduncle Evaluated with Magnetic Resonance Imaging.

Remyelination is common under physiological conditions and usually occurs as a response to a pathological demyelinating event. Its potentiation is an important goal for the development of therapies against pathologies such as multiple sclerosis and white matter injury. Visualization and quantification in vivo of demyelination and remyelination processes are essential for longitudinal studies that will allow the testing and development of pro-myelinating strategies. In this study, ethidium bromide (EB) was stereotaxically injected into the caudal cerebellar peduncle (c.c.p.) in rats to produce demyelination; the resulting lesion was characterized (i) transversally through histology using Black-Gold II (BGII) staining, and (ii) longitudinally through diffusion-weighted magnetic resonance imaging (dMRI), by computing fractional anisotropy (FA) and diffusivity parameters to detect microstructural changes. Using this characterization, we evaluated, in the lesioned c.c.p., the effect of N-butyl-ß-carboline-3-carboxylate (ß-CCB), a potentiator of GABAergic signaling in oligodendrocytes. The dMRI analysis revealed significant changes in the anisotropic and diffusivity properties of the c.c.p. A decreased FA and increased radial diffusivity (λ⊥) were evident following c.c.p. lesioning. These changes correlated strongly with an apparent decrease in myelin content as evidenced by BGII. Daily systemic ß-CCB administration for 2 weeks in lesioned animals increased FA and decreased λ⊥, suggesting an improvement in myelination, which was supported by histological analysis. This study shows that structural changes in the demyelination-remyelination of the caudal cerebellar peduncle (DRCCP) model can be monitored longitudinally by MRI, and it suggests that remyelination is enhanced by ß-CCB treatment. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.

Validation of Electroencephalographic Recordings Obtained with a Consumer-Grade, Single Dry Electrode, Low-Cost Device: A Comparative Study.

The functional validity of the signal obtained with low-cost electroencephalography (EEG) devices is still under debate. Here, we have conducted an in-depth comparison of the EEG-recordings obtained with a medical-grade golden-cup electrodes ambulatory device, the SOMNOwatch + EEG-6, vs those obtained with a consumer-grade, single dry electrode low-cost device, the NeuroSky MindWave, one of the most affordable devices currently available. We recorded EEG signals at Fp1 using the two different devices simultaneously on 21 participants who underwent two experimental phases: a 12-minute resting state task (alternating two cycles of closed/open eyes periods), followed by 60-minute virtual-driving task. We evaluated the EEG recording quality by comparing the similarity between the temporal data series, their spectra, their signal-to-noise ratio, the reliability of EEG measurements (comparing the closed eyes periods), as well as their blink detection rate. We found substantial agreement between signals: whereas, qualitatively, the NeuroSky MindWave presented higher levels of noise and a biphasic shape of blinks, the similarity metric indicated that signals from both recording devices were significantly correlated. While the NeuroSky MindWave was less reliable, both devices had a similar blink detection rate. Overall, the NeuroSky MindWave is noise-limited, but provides stable recordings even through long periods of time. Furthermore, its data would be of adequate quality compared to that of conventional wet electrode EEG devices, except for a potential calibration error and spectral differences at low frequencies.

Post-transplant lymphoproliferative disorders after solid organ and hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorders (PTLD) are a rare complication after both solid organ (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single center retrospective study, we compared clinical, biological, and histological features, and outcomes of PTLD after both types of transplant. We identified 82 PTLD (61 after SOT and 21 after allo-HSCT). The presence of B symptoms, Waldeyer ring, spleen, central nervous system, and liver involvement, and advanced Ann-Arbor stage were more frequent in allo-HSCT recipients. PTLD had an earlier onset in allo-HSCT than in SOT cohort (4 vs. 64 months, p < .0001). PTLD was EBV-positive in 100% of allo-HSCT, in contrast to 47% of SOT (p = .0002). Four years after PTLD diagnosis, median overall survival was 32% (95% CI, 22-48) and 10% (95% CI, 2-49) in SOT and allo-HSCT recipients, respectively (p = .002). In conclusion, the clinical presentation and the outcome of PTLD varies greatly depending on the type of transplant.

Guía práctica de tratamiento urgente de la microangiopatía trombótica / Practice guidelines for the emergency treatment of thrombotic microangiopathy

Antecedentes y objetivo: El término microangiopatía trombótica (MAT) incluye un grupo heterogéneo de enfermedades potencialmente mortales o invalidantes, rápidamente evolutivas, caracterizadas por anemia hemolítica microangiopática y trombocitopenia. La actuación en las primeras horas es crucial para mejorar el pronóstico de los pacientes. El objetivo de esta revisión es proporcionar recomendaciones orientadas a optimizar el tratamiento inicial de la MAT y agilizar el diagnóstico etiológico. Pacientes y métodos: Se diseña una guía práctica en la cual se diferencian cuatro apartados en el abordaje inicial de las MAT: sospecha diagnóstica, confirmación sindrómica, tratamiento urgente y estudios complementarios. Resultados: La detección de anemia hemolítica microangiopática (caracterizada por aumento de reticulocitos, LDH y bilirrubina indirecta, Coombs directo negativo y esquistocitos en el frotis de sangre periférica) y trombocitopenia no justificable por otras causas secundarias confirma el diagnóstico sindrómico de anemia hemolítica microangiopática y trombocitopenia (AHMAT). Estos pacientes requieren ingreso en la unidad de cuidados intensivos para iniciar lo antes posible el recambio plasmático, preferiblemente en las primeras 4-8h. Antes de realizar el recambio plasmático deben extraerse las muestras para el estudio de ADAMTS13 y de complemento. Finalmente, es importante solicitar las pruebas complementarias necesarias para obtener un correcto diagnóstico etiológico. Conclusiones: La puesta en práctica de las recomendaciones consensuadas en esta guía permitirá mejorar los resultados terapéuticos al facilitar la cooperación de los distintos especialistas implicados en la atención de las MAT

Background and aim: The term thrombotic microangiopathy (TMA) involves a heterogeneous group of diseases that can be overwhelming or invalidating, with an acute development, characterised by microangiopathic haemolytic anaemia and thrombocytopaenia. Its management during its initial hours is essential to improving the prognostic of these patients. The aim of this review is to give recommendations about the optimisation of TMA initial treatment and to accelerate the aetiological diagnosis. Patients and methods: We provide a practice guideline based on four steps for the initial management of TMA: diagnosis of suspicion, syndromic confirmation, emergent treatment and complementary tests. Results: The detection of microangiopathic haemolytic anaemia (characterised by elevated reticulocytes, LDH and indirect bilirubin, negative direct Coombs test and schistocytes in peripheral blood), and thrombocytopaenia not explained by other secondary aetiologies confirm the syndromic diagnosis of microangiopathic haemolytic anaemia and thrombocytopaenia (MAHAT). These patients require admission to an Intensive Care Unit to initiate plasma exchange therapy as soon as possible, ideally within the first 4-8hours. Prior to this, samples for ADAMTS13 and complement study should be obtained. Finally, it is important to request the complementary tests necessary to have a correct aetiological diagnosis. Conclusions: Adherence to the agreed recommendations in this guideline will improve therapeutic results by facilitating cooperation between different specialists involved in TMA management

Practice guidelines for the emergency treatment of thrombotic microangiopathy. / Guía práctica de tratamiento urgente de la microangiopatía trombótica.

BACKGROUND AND AIM: The term thrombotic microangiopathy (TMA) involves a heterogeneous group of diseases that can be overwhelming or invalidating, with an acute development, characterised by microangiopathic haemolytic anaemia and thrombocytopaenia. Its management during its initial hours is essential to improving the prognostic of these patients. The aim of this review is to give recommendations about the optimisation of TMA initial treatment and to accelerate the aetiological diagnosis. PATIENTS AND METHODS: We provide a practice guideline based on four steps for the initial management of TMA: diagnosis of suspicion, syndromic confirmation, emergent treatment and complementary tests. RESULTS: The detection of microangiopathic haemolytic anaemia (characterised by elevated reticulocytes, LDH and indirect bilirubin, negative direct Coombs test and schistocytes in peripheral blood), and thrombocytopaenia not explained by other secondary aetiologies confirm the syndromic diagnosis of microangiopathic haemolytic anaemia and thrombocytopaenia (MAHAT). These patients require admission to an Intensive Care Unit to initiate plasma exchange therapy as soon as possible, ideally within the first 4-8hours. Prior to this, samples for ADAMTS13 and complement study should be obtained. Finally, it is important to request the complementary tests necessary to have a correct aetiological diagnosis. CONCLUSIONS: Adherence to the agreed recommendations in this guideline will improve therapeutic results by facilitating cooperation between different specialists involved in TMA management.

Nível de letramento funcional em saúde e comportamento em saúde de idosos / Nivel de alfabetización funcional en salud: y comportamiento en salud de idosos / Functional health literacy level and behavior in the health of the elderly

RESUMO Objetivo: avaliar o nível de letramento funcional em saúde de idosos e discutir sua influência no comportamento de saúde destes idosos. Método: estudo transversal, exploratório-descritivo, caracterizado como desenho misto de pesquisa, modelo de convergência. A coleta de dados, realizada ente agosto e novembro de 2016, aconteceu nos domicílios de 175 residentes na zona urbana de município do interior do Estado do Rio Grande do Sul (Brasil), idosos por meio da aplicação do instrumento S-TOFHLA, destes, dez responderam a entrevista aberta sobre comportamento em saúde. Para análise dos dados foram utilizados, os testes qui quadrado de Pearson; exato de Fisher α=5% e p≤0,05; e análise temática de conteúdo. Resultados: o nível de letramento funcional em saúde demonstrou-se inadequado em 39,4% dos idosos. Houve associação entre o letramento funcional em saúde e as variáveis sexo; faixa etária; escolaridade e número de filhos (p≤0,005). A categoria Comportamento em saúde subdividiu-se nas subcategorias: Papel do profissional de saúde, Suporte familiar e de amigos, Costume e subjetividade, com transversalidade do letramento funcional em saúde. Conclusão: este estudo reiterou a importância da avaliação do nível de letramento funcional em saúde na assistência global do idoso como iniciativa relevante para adequação do planejamento de ações e comportamentos em saúde, visando melhores resultados na produção do cuidado.

RESUMEN Objetivo: evaluar el nivel de alfabetización funcional en salud de ancianos y discutir su influencia en el comportamiento de salud de estos ancianos. Método: estudio transversal, exploratorio-descriptivo, caracterizado como diseño mixto de investigación, modelo de convergencia. La recolección de datos, realizada en agosto y noviembre de 2016, ocurrió en los domicilios de 175 residentes en la zona urbana de municipio del interior del Estado de Rio Grande do Sul (Brasil), ancianos por medio de la aplicación del instrumento S-TOFHLA, de éstos, diez respondieron la entrevista abierta sobre comportamiento en salud. Para el análisis de los datos se utilizaron, las pruebas qui cuadrado de Pearson; exacto de Fisher α=5% y p≤0,05; y el análisis temático de contenido. Resultados: el nivel de alfabetización funcional en salud se demostró inadecuado en el 39,4% de los ancianos. Se observó asociación entre el fonograma funcional en salud y las variables sexo; grupo de edad; escolaridad y número de hijos (p≤0,005). La categoría Comportamiento en salud se subdividió en las subcategorías: Papel del profesional de salud, Apoyo familiar y de amigos, Costumbre y subjetividad, con transversalidad de Alfabetización funcional en salud. Conclusión: este estudio reiteró la importancia de la evaluación del nivel de Alfabetización funcional en salud en la asistencia global del anciano como iniciativa relevante para adecuación de la planificación de acciones y comportamientos en salud, buscando mejores resultados en la producción del cuidado.

ABSTRACT Objective: to evaluate the level of functional health literacy in elderly people and to discuss its influence on the health behaviour of these people. Method: a cross-sectional, exploratory-descriptive study, characterized as mixed research design, convergence model. Data collection was carried out between August and November 2016 and occurred in the homes of 175 residents in the inner cities of the State of Rio Grande do Sul (Brazil), classified as elderly by the application of the S-TOFHLA instrument, of which ten answered the open interview on health behaviour. The Pearson's chi-square test; Fisher's exact α = 5% and p≤0.05; and thematic content analysis were used for data analysis. Results: the functional health literacy level was inadequate in 39.4% of the elderly study participants. There was an association between functional health literacy and gender variables; age group; schooling and number of children (p≤0.005). The Health Behaviour category was subdivided into the subcategories: Role of the health professional, Family and friends support, Custom and subjectivity, with transversality4 of functional health literacy. Conclusion: This study reiterated the importance of evaluating the level of functional health literacy in the overall care of the elderly person as a relevant initiative to adequately plan health actions with the aim to improve results in the production of care.

Monitoring driver fatigue using a single-channel electroencephalographic device: A validation study by gaze-based, driving performance, and subjective data.

Driver fatigue can impair performance as much as alcohol does. It is the most important road safety concern, causing thousands of accidents and fatalities every year. Thanks to technological developments, wearable, single-channel EEG devices are now getting considerable attention as fatigue monitors, as they could help drivers to assess their own levels of fatigue and, therefore, prevent the deterioration of performance. However, the few studies that have used single-channel EEG devices to investigate the physiological effects of driver fatigue have had inconsistent results, and the question of whether we can monitor driver fatigue reliably with these EEG devices remains open. Here, we assessed the validity of a single-channel EEG device (TGAM-based chip) to monitor changes in mental state (from alertness to fatigue). Fifteen drivers performed a 2-h simulated driving task while we recorded, simultaneously, their prefrontal brain activity and saccadic velocity. We used saccadic velocity as the reference index of fatigue. We also collected subjective ratings of alertness and fatigue, as well as driving performance. We found that the power spectra of the delta EEG band showed an inverted U-shaped quadratic trend (EEG power spectra increased for the first hour and half, and decreased during the last thirty minutes), while the power spectra of the beta band linearly increased as the driving session progressed. Coherently, saccadic velocity linearly decreased and speeding time increased, suggesting a clear effect of fatigue. Subjective data corroborated these conclusions. Overall, our results suggest that the TGAM-based chip EEG device is able to detect changes in mental state while performing a complex and dynamic everyday task as driving.

Infections of the Central Nervous System after Unrelated Donor Umbilical Cord Blood Transplantation or Human Leukocyte Antigen-Matched Sibling Transplantation.

We analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (CNS) infections in consecutive patients with receiving umbilical cord blood transplantation (UCBT) (n = 343) or HLA-matched sibling donor stem cell transplantation (MST) (n = 366). Thirty-four CNS infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). The cumulative incidence (CI) risk of developing a CNS infection was .6% at day +30, 2.3% at day +90, and 4.9% at 5 years. The 5-year CI of CNS infection was 8.2% after UCBT and 1.7% after MST (P < .001). The causative micro-organisms of CNS infections were fungi (35%), virus (32%), Toxoplasma spp. (12%), and bacteria (12%). Fungal infections occurred in 11 patients after UCBT and 1 after MST and were due to Aspergillus spp. (n = 8), Cryptococcus neoformans (n = 2), Scedosporium prolificans (n = 1), and Mucor (n = 1). Except for 1 patient, all died from CNS fungal infection. Viral infections occurred in 9 patients after UCBT and 1 after MST and were due to human herpes virus 6 (n = 7), cytomegalovirus (n = 2), and varicella zoster virus (n = 1). CNS toxoplasmosis was diagnosed in 3 patients after UCBT and 1 after MST. Other pathogens were Staphylococcus spp, Nocardia spp, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Twenty of the 34 patients (59%) died from the CNS infection. In multivariable analysis, UCBT and disease stage beyond first complete remission were independently associated with the risk of developing CNS infections. The 5-year overall survival was 19% in patients who developed a CNS and 39% for those who did not (P = .006). In conclusion, our study showed that CNS infections are a significant clinical problem after stem cell transplantation associated with poor survival. They were more frequent after UCBT compared to MST.