Subacute Liver Failure Following Gene Replacement Therapy for Spinal Muscular Atrophy Type 1.

Spinal muscular atrophy is a neurodegenerative disease resulting from irreversible loss of anterior horn cells owing to biallelic deletions/mutations in the survival motor neuron (SMN) 1 gene. Gene replacement therapy using an adeno-associated virus vector containing the SMN gene was approved by the US Food and Drug Administration in May 2019. We report 2 cases of transient, drug-induced liver failure after this therapy.

Brazilian Portuguese version of the Patient Competency Rating Scale (PCRS-R-BR): semantic adaptation and validity / Versão em português brasileiro da Patient Competency Rating Scale (PCRS-R-BR): adaptação semântica e validade

This study describes the adaptation of a revised Brazilian version of the Patient Competency Rating Scale (PCRS-R-BR), which focuses on executive, mnemonic, and attention functions. Evidence of content-based and external validity is also reported. The cross-cultural adaptation was conducted in five phases: 1) translations and back translations; 2) item analysis by authors; 3) classification by experts; 4) revisions and reformulations by authors; 5) pilot study with a sample of patients with mild and moderate/severe traumatic brain injury (TBI). Data were analyzed descriptively, and the PCRS-R-BR scores of groups with mild vs. moderate/severe TBI were compared using the Mann-Whitney test. Patients and their relatives were divided into groups and compared using repeated-measures analysis. The results of the PCRS-R-BR questionnaire for relatives and discrepancy scores of patients with moderate/severe TBI revealed significantly more impairment than that found in the group of patients with mild TBI. There were significant differences between item and total scores of both groups of patients and relatives. Results indicated a high level of item content agreement between experts. This study found initial evidence of PCRS-R-BR content-based and external validity when the questionnaire was applied to patients with mild and moderate/severe TBI and their relatives.

O presente artigo teve como objetivo apresentar a adaptação transcultural e evidências de validade externa e de conteúdo da versão brasileira revisada da Patient Competency Rating Scale (PCRS-R-BR), com foco nas funções executivas, mnemônicas e atencionais. A adaptação transcultural incluiu cinco fases: 1) tradução e retrotradução; 2) análise de itens por autores; 3) análise de especialistas; 4) revisões e reformulações dos autores; 5) estudo piloto em pacientes com traumatismo cranioencefálico (TCE) leve e moderado/grave. Os dados foram analisados descritivamente e os pacientes com TCE leve e moderado/grave foram comparados nos escores da PCRS-R-BR pelo teste Mann-Whitney. Os pacientes e familiares foram comparados por grupo através da análise de medidas repetidas. Os pacientes com TCE moderado/grave tiveram maior prejuízo que os pacientes com TCE leve no formulário da PCRS-R-BR dos familiares e no escore de discrepância entre pacientes e familiares. Os resultados indicam bons e altos níveis de concordância entre especialistas frente aos componentes avaliados pelos itens. Esse estudo apresentou evidências iniciais de validade de conteúdo da PCRS-R-BR para pacientes com TCE leve e moderado/severo e seus familiares.

Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial.

OBJECTIVE: To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. METHODS: We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. RESULTS: Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced > or =50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. CONCLUSION: Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease. METHODS: In a 76-week, double-blind, placebo-controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8-week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high-affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent-to-treat population and the high-affinity population. RESULTS: Anti-double-stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent-to-treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high-dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high-affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels >/=1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high-affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394-treated patients (21.9%) and 34 of the 116 placebo-treated patients (29.3%). CONCLUSION: Treatment with LJP 394 in patients with high-affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.