Molecular genetic analyses in familial and sporadic congenital primary erythrocytosis

Dominant mutations in the erythropoietin receptor (EPOR) gene account for only about 15% of cases of primary congenital erythrocytosis. To search for molecular alterations in patients with this disorder. Sixteen patients with Ep

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

O uso de praças públicas como espaço não formal de educação

Dentre os desafios para a implantação da escola de tempo integral no Brasil, está a falta de espaço físico nas escolas. O Plano Nacional de Educação (2014-2024) propõe como uma das estratégias para a resolução desta questão, a articulação da escola com os diferentes espaços educativos, culturais e esportivos, alinhando educação formal com educação em espaço não formal, ou seja, fora dos muros da escola.  Com o intuito de contribuir com este processo, se iniciou em 2015 um projeto de extensão, na forma de oficinas para o ensino de ciências, nas dependências da Praça do Parcão (Praça Dom Pedro II) no município de Uruguaiana-RS, tendo como um dos objetivos, contribuir com a implantação da escola de tempo integral oferecendo atividades educativas em espaços não formais. Nas análises das avaliações dos educandos, se observa que a metodologia de ensino proporcionou aprendizagem, contribuiu com a formação dos alunos, que os temas explorados durante as atividades despertam o interesse, contribuem com a mudança dos olhares sobre a praça e agregam conhecimentos. Estes resultados corroboram com a possibilidade de utilização dos espaços públicos (praças) como ferramenta para o processo de ensino-aprendizagem. Palavras-chave: espaço não-formal; ensino de ciências; praças públicas

O uso de praças públicas como espaço não formal de educação

Dentre os desafios para a implantação da escola de tempo integral no Brasil, está a falta de espaço físico nas escolas. O Plano Nacional de Educação (2014-2024) propõe como uma das estratégias para a resolução desta questão, a articulação da escola com os diferentes espaços educativos, culturais e esportivos, alinhando educação formal com educação em espaço não formal, ou seja, fora dos muros da escola. Com o intuito de contribuir com este processo, se iniciou em 2015 um projeto de extensão, na forma de oficinas para o ensino de ciências, nas dependências da Praça do Parcão (Praça Dom Pedro II) no município de Uruguaiana-RS, tendo como um dos objetivos, contribuir com a implantação da escola de tempo integral oferecendo atividades educativas em espaços não formais. Nas análises das avaliações dos educandos, se observa que a metodologia de ensino proporcionou aprendizagem, contribuiu com a formação dos alunos, que os temas explorados durante as atividades despertam o interesse, contribuem com a mudança dos olhares sobre a praça e agregam conhecimentos. Estes resultados corroboram com a possibilidade de utilização dos espaços públicos (praças) como ferramenta para o processo de ensino-aprendizagem

Idiopathic hypereosinophilic syndrome in children: report of a 7-year-old boy with FIP1L1-PDGFRA rearrangement

Idiopathic hypereosinophilic syndrome (HES) in children is a very rare disorder; certain clinical differences with adult HES have been described, with no pediatric case with the imatinib-responsive FIP1L1-PDGFRA fusion gene reported to date. The authors describe the clinical course of three children with HES in whom FIP1L1-PDGFRA fusion gene was studied and report the first child with this rearrangement

Evacuation of intracerebral hemorrhages by neuroendoscopy with transparent sheath. Experimental study

Objectives: Endoscopic evacuation of intracerebral hemorrhage (ICH) has been developed in order to reduce the tissue injury that conventional craniotomy could generate. Experimental studies are important to assess the effectiveness of the technique and its modifications. The objectives of this study are to develop in pig an experimental model of endoscopic evacuation of ICHs, to assess effectiveness of surgical evacuation, and to evaluate a new transparent sheath as complement to the endoscopy. Methods: Autologous blood was infused into the frontal lobe white matter in 16 pigs. In the problem group, endoscopic evacuation was performed with the aid of a new transparent sheath, which has outer and inner sheaths with blunt and closed finals. Pigs were sacrificed at 4 h, 24 h and 5 days. The volumes of hematoma and histopathological features were determined. Results: Residual volume of the problem group was significantly 70.09% lower than in control group, without significant differences in injected volumes, in percentage of subarachnoid hemorrhage, and in time interval from hematoma induction to pig´s death. The vital reaction after hemorrhage was similar in both groups. Conclusions: The experimental model developed is useful to assess endoscopic evacuation of ICHs. The endoscopy is an effective technique in the treatment of ICHs, without increasing the vital reaction secondary to hematoma. The new transparent sheath increases the visualization of surgical field and allows a continuous visual control since the beginning of the procedure. Its closed final prevents unwanted injury of the brain by the instruments used to remove the hematoma