Transfusion Monitoring: Care Practice Analysis In A Public Teaching Hospital

To analyze the process of recording transfusion monitoring at a public teaching hospital. Methods: A descriptive and retrospective study with a quantitative approach, analyzing the instruments to record transfusion monitoring at a public hospital in a city in the State of Minas Gerais (MG). Data were collected on the correct completion of the instrument, time elapsed from transfusions, records of vital signs, type of blood component more frequently transfused, and hospital unit where transfusion was performed. Results: A total of 1,012 records were analyzed, and 53.4% of them had errors in filling in the instruments, 6% of transfusions started after the recommended time, and 9.3% of patients had no vital signs registered. Conclusion: Failures were identified in the process of recording transfusion monitoring, and they could result in more adverse events related to the administration of blood components. Planning and implementing strategies to enhance recording and to improve care delivered are challenging.141414

Monitorização transfusional: análise da prática assistencial em um hospital público de ensino

Objective To analyze the process of recording transfusion monitoring at a public teaching hospital. Methods A descriptive and retrospective study with a quantitative approach, analyzing the instruments to record transfusion monitoring at a public hospital in a city in the State of Minas Gerais (MG). Data were collected on the correct completion of the instrument, time elapsed from transfusions, records of vital signs, type of blood component more frequently transfused, and hospital unit where transfusion was performed. Results A total of 1,012 records were analyzed, and 53.4% of them had errors in filling in the instruments, 6% of transfusions started after the recommended time, and 9.3% of patients had no vital signs registered. Conclusion Failures were identified in the process of recording transfusion monitoring, and they could result in more adverse events related to the administration of blood components. Planning and implementing strategies to enhance recording and to improve care delivered are challenging.Objetivo Analisar o processo de registro de monitorização do ato transfusional em um hospital público de ensino. Métodos Estudo descritivo, retrospectivo, de abordagem quantitativa. Foram analisados os instrumentos de registro de monitorização do ato transfusional em um hospital público do interior de Minas Gerais (MG). Foram coletados dados relativos a correto preenchimento do instrumento, tempo decorrido das transfusões, registros dos sinais vitais, tipo de hemocomponente mais frequentemente transfundido e setor de ocorrência da transfusão. Resultados Foram analisados 1.012 instrumentos, dos quais 53,4% apresentaram falhas no preenchimento, 6% das infusões foram iniciadas após o tempo preconizado e 9,3% dos pacientes não tiveram os sinais vitais registrados. Conclusão Foram identificadas falhas no processo de registro da monitorização transfusional, que podem gerar maior ocorrência de eventos adversos relacionados à administração de hemocomponentes. É um desafio elaborar e implementar estratégias que possibilitem aprimorar os registros, assim como a assistência prestada.141414

Estudo anatomofisiológico de um feto com Síndrome de Potter ou Meckel-Gruber: diagnóstico diferencial

Introdução: As síndromes genéticas de Meckel-Gruber e a de Potter têm prevalência de até 1 para cada 2000 nascimentos, sendo então consideraras condições raras, de acordo com a Rare Disease International. Objetivo: Relatar um caso de Síndrome de Meckel-Gruber e demonstrar as principais diferenças entre esta e a Síndrome de Potter. Métodos: Relato de caso de um feto com 32 semanas, do sexo feminino com inúmeras malformações, cujos progenitores eram consanguíneos. O óbito ocorreu após 40 minutos de vida. Foi realizada dissecção anatômica e análise histomorfológica de encéfalo, fígado, estômago, intestinos, baço, pâncreas, vesícula biliar, rins, pulmões, coração, diafragma, útero, membros superiores e inferiores. Resultados: As principais características encontradas foram hipoplasia pulmonar, cardiomegalia, timo e rim direito aumentados, hepatomegalia, hipertelorismo, dobras epicânticas, orelhas de implantação baixa, queixo recuado, nariz largo e achatado, abdome volumoso com excesso de pele, joelhos varos com pés equinovaros e encefalocele. Estudo citogenético diagnosticou a Síndrome de Meckel-Gruber. Os órgão acometidos foram analisados histologicamente. Discussão: A consanguinidade é relatada como fator de risco para as malformações genéticas e estava presente neste caso. Inicialmente, a hipótese era de Síndrome de Potter devido às características faciais. No entanto, após o resultado da análise genética, confirmou-se a Síndrome de Meckel -Gruber. Uma das principais diferenças entre as duas síndromes são as alterações renais. Foram observadas formações císticas nos túbulos proximais e parênquima renal alterado. Na Síndrome de Potter, pode ocorrer agenesia renal e rins policísticos. Conclusão:  O estudo detalhado deste feto enriqueceu o conhecimento prévio da Síndrome de Meckel-Gruber, possibilitando um aconselhamento genético mais adequado aos pais e uma reflexão mais assertiva sobre futuras gestações

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk