Objectives: A mortality rate of non-human immunodeficiency virus-infected pneumocystis pneumonia (non-HIV PCP) is 30-60%. But the effectiveness of adjunctive corticosteroids with trimethoprimsulfamethoxazole has been unclear, and we examined whether it lowered risk of mortality in non-HIV PCP. Methods: We did an observational study of adult non-HIV PCP patients from April 2010 through March 2016, using Japanese nationwide healthcare records of the Diagnostic Procedure Combination database (DPC). The risk was estimated by the time-dependent Cox regression analyses with inverse probability weights. Result: 1299 eligible non-HIV PCP patients were identified. 737 patients were severe respiratory status (partial pressure of oxygen in arterial blood [PaO 2 ] 60 mm Hg) and 562 were moderate (PaO 2 >60 mm Hg) at hospital admission. Among patients with severe respiratory status, the adjunctive corticosteroids was associated with lower risk of 60-day mortality (HR 0.71; 95% confidence interval [CI], 0.55-0.91), and significantly decreased mortality rates (24.7% vs 36.6%, P = 0.006). In contrast, no significant differences were observed in the risk of 60-day mortality (HR 1.17; 95% CI, 0.73-1.86) and the mortality rate (10.9% vs 9.1%, P = 0.516) among patients with moderate respiratory status. Conclusion: The adjunctive corticosteroids were associated with lower risk of 60-day mortality in severe non-HIV PCP patients.

ERK (extracellular signal-regulated kinase) plays a central role in signal transduction networks and cell fate decisions. Sustained ERK activation induces cell differentiation while transient ERK results in proliferation of several types of cells. Sustained ERK activity stabilizes proteins of early response gene products. However, the effect of ERK activity duration on mRNA stability is unknown. We analyzed the quantitative relationship between duration of four ERK activity kinetics and mRNA expression profile in growth factors treated cells. Time-course transcriptome analysis revealed that the cells with prolonged ERK activity generally show sustained mRNA expression of late response genes, but not early- or mid-genes. Selected late response genes decayed more rapidly in the presence of a specific ERK inhibitor than a general transcription inhibitor and the decay rate was not related to the number of AU-rich elements. Our results suggest that sustained ERK activity plays an important role in lifespan of the mRNA encoded by late response genes, in addition to previously demonstrated role in protein stabilization of early response genes including transcription factors regulating transcription of mid- and late-genes. This double positive regulation of ligand-induced genes, also called feedforward regulation, is critical in cell fate decisions.

The risk of hepatitis B virus (HBV) reactivation has increased owing to advances in the immunosuppressive therapy field. However, the HBV reactivation incidence among patients with previously resolved HBV (prHBV) infection during immunosuppressive therapy for rheumatoid arthritis (RA) remains unclear. The objective of this work is to describe the validity of detecting prHBV infection from administrative data through comparisons with chart abstraction and determine the incidence of HBV reactivation during immunosuppressive therapy for RA in Japan. In this retrospective cohort study, data on selected patients were extracted from administrative claims data. To identify patients with prHBV infection and de novo hepatitis, and HBsAg carriers, we conducted chart abstraction. The incidence rate of de novo hepatitis was 1.23 of 100 person‐years. The positive predictive value (PPV) and its 95% confidence interval (CI) of administrative data for the identification of suspected prHBV infections was 85.8% (95% CI: 81.7%‐89.3%). This study evaluated the PPV of the algorithm of HBV‐DNA testing with immunosuppressive therapy performed four times or more per year for the detection of prHBV infection from administrative data. Additionally, we determined the incidence rate of HBV reactivation among preHBV infections during immunosuppressive therapy for RA to be 1.23 of 100 person‐years.