RESUMO
INTRODUCTION: We investigated short and long-term remission rates after splenectomy in patients with primary and secondary autoimmune hemolytic anemia (AIHA). METHODS: All adults who underwent splenectomy for primary or secondary AIHA at a single center (2004-2018) were retrospectively reviewed. Short-term response was determined at 30-day postoperatively and long-term at one year. Complete response was defined as hemoglobin > 10 g/dL without hemolysis, transfusions, or need for additional medical therapy for > 6 months. RESULTS: Short-term complete response was attained in 22 of 36 patients (61%), partial response in 3 (8%), no response in 11 (31%). The response rate at 1 year was complete in 14/36 (39%), partial in 14 (39%), and 8 non-response (22%). At last available follow-up (median 33.1 months (IQR 19-59), 16/37 patients had experienced a complete response (43%), 14 partial response (38%), 7 non-response (19%). 80% of partial responders with primary AIHA required maintenance therapy compared to 100% with secondary AIHA. CONCLUSION: Splenectomy is associated with short- and long-term improvement in anemia and hemolysis in the majority of patients with AIHA. Immunosuppressants remain important supplemental therapy.
Assuntos
Anemia Hemolítica Autoimune , Adulto , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/cirurgia , Hemólise , Humanos , Estudos Retrospectivos , Esplenectomia , Resultado do TratamentoRESUMO
Sertraline is used for the treatment of depression, and is also used for the treatment of panic, obsessive-compulsive, and post-traumatic stress disorders. Previously, we have demonstrated that sertraline caused hepatic cytotoxicity, with mitochondrial dysfunction and apoptosis being underlying mechanisms. In this study, we used microarray and other biochemical and molecular analyses to identify endoplasmic reticulum (ER) stress as a novel molecular mechanism. HepG2 cells were exposed to sertraline and subjected to whole genome gene expression microarray analysis. Pathway analysis revealed that ER stress is among the significantly affected biological changes. We confirmed the increased expression of ER stress makers by real-time PCR and Western blots. The expression of typical ER stress markers such as PERK, IRE1α, and CHOP was significantly increased. To study better ER stress-mediated drug-induced liver toxicity; we established in vitro systems for monitoring ER stress quantitatively and efficiently, using Gaussia luciferase (Gluc) and secreted alkaline phosphatase (SEAP) as ER stress reporters. These in vitro systems were validated using well-known ER stress inducers. In these two reporter assays, sertraline inhibited the secretion of Gluc and SEAP. Moreover, we demonstrated that sertraline-induced apoptosis was coupled to ER stress and that the apoptotic effect was attenuated by 4-phenylbutyrate, a potent ER stress inhibitor. In addition, we showed that the MAP4K4-JNK signaling pathway contributed to the process of sertraline-induced ER stress. In summary, we demonstrated that ER stress is a mechanism of sertraline-induced liver toxicity.