RESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.
Assuntos
Anticorpos Antinucleares/sangue , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/antagonistas & inibidores , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Direct enzymatic assay of urinary sulfated bile acids is a sensitive, rapid, minimally invasive, and convenient method of detecting cholestasis in young infants. It may replace measurement of serum direct bilirubin for selective screening for biliary atresia and neonatal hepatitis syndrome at 1 month of age.
Assuntos
Ácidos e Sais Biliares/urina , Bilirrubina/sangue , Colestase/diagnóstico , Triagem Neonatal , Atresia Biliar/sangue , Atresia Biliar/diagnóstico , Atresia Biliar/urina , Colestase/sangue , Colestase/urina , Feminino , Hepatite/sangue , Hepatite/diagnóstico , Hepatite/urina , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Sulfatos/urina , SíndromeRESUMO
Efficacy of short atrioventricular (AV) delay and diastolic mitral regurgitation (MR) were studied in 16 patients (70.2 mais ou menos 10.5 SD years old) with implanted DDD pacemakers. AV delay was set at 0.215 and 0.115 sec. In 10 of the 16 patients, diastolic MR was not observed when the AV delay was set at both 0.215 and 0.115 sec. Cardiac output (CO) and pulmonary capilary wedge pressure (PCWP) did not change.In 6 of the 16 patients, diastolic MR was observed when the AV delay was set a 0.215 se However, diastolic MR was not observed when the AV delay was set at 0.115 sec. CO increased from 3.6 mais ou menos 0.7 to 3.9 mais ou menos 0.8 I/min (p menor que 0.05). PCWP was decreased in 5 of the 6 patients (83 por cento, p menor que 0.05 vs. 10 por cento in patients without diastolic MR at 0.215 sec of AV delay). Cardiac function may be improved by shortening AV delay when the diastolic MR was observed. On the other hand, short AV delay may not be effective for patients in whom diastolic MR was ntobserved.