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Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by dysregulation of fibroblast function, which often involves the lungs. Interstitial lung disease (ILD) associated with SSc (SSc-ILD) is a major cause of death among patients with SSc. Our study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with SSc-ILD. Patients were retrospectively enrolled between 2010 and 2018 in a tertiary hospital in Korea. Patients with SSc-ILD were classified depending on the first pulmonary function test or radiologic findings: extensive (n = 46, >20% disease extent on computed tomography (CT) or forced vital capacity [FVC] < 70% in indeterminate cases) and limited (n = 60, <20% disease extent on CT or FVC ≥70% in indeterminate cases). Patients in the extensive group were younger (mean age ± SD 49.3 ± 11.5) than those in the limited group (53.9 ± 12.5, p =.067) at diagnosis. The extensive group showed frequent pulmonary hypertension (43.5% vs. 16.7%, p =.009) and higher erythrocyte sedimentation rate (61.3 ± 33.7 vs. 42.1 ± 26.0, p =.003) and mortality (32.6%, mean duration of follow-up, 100.0 ± 44.7 months vs. 10.0%, 86.0 ± 53.4 months, p =.011). ILD was detected within five years from the first visit (median years 3.5 (1.0, 6.0) vs. 4.5 (0.6, 9.0), survivors vs. non-survivors), and mortality occurred in 19.8% of all patients during a 15-year follow-up. Older age, lower FVC, and initial disease stage (limited or extensive) were associated with mortality, but FVC decline was similar in the limited and extensive groups, such as 15–20% in the first year and 8–10% in the next year, regardless of the initial extent of the disease. Approximately 10% of patients with SSc-ILD in the limited and extensive group showed progression. ILD was detected at a median of less than five years from the first visit; therefore, it is necessary to carefully monitor patients' symptoms and signs from an early stage. Long-term surveillance is also required. Patients with systemic sclerosis-interstitial lung disease manifested a heterogeneous disease course. Approximately 10% of the patients in the limited group showed progression, which was similar to the proportion of patients in the extensive group. Interstitial lung disease was detected at a median of less than five years from the first visit. [ABSTRACT FROM AUTHOR]

Detection rate of de novo EGFR T790 M mutation was increased up to 80% through recent ultrasensitive detection methods. Here, we investigated the clinical significance and its usefulness of detecting de novo EGFR T790 M using ultrasensitive droplet-digital polymerase chain reaction (ddPCR) method. In total, 102 cases diagnosed as lung adenocarcinoma with EGFR-tyrosine kinase inhibitor (TKI) sensitizing mutations (mEGFR) and had been treated with 1st ~ 2nd generation EGFR-TKI alone were enrolled for this study. De novo T790 M status was tested using the tissues at the initial diagnosis and positivity was defined as the ratio of T790 M/wild-type copies over 0.00294 by ddPCR. Seventy patients (68.6%) harbored the de novo T790 M. De novo T790 M was more frequently detected in cases with EGFR L858 R mutation than those with EGFR exon 19 deletion (E19d) mutations (P = 0.024). Forty-three patients underwent rebiopsy due to disease progression. The cases who experienced progression due to acquired T790 M were more likely to have E19d at initial diagnosis and the presence of de novo T790 M and the ratio of T790 M/wild-type copies did not relate to the emergence of acquired T790 M. On the other hand, the cases with a longer duration of disease-control by EGFR-TKI had higher change to get acquired T790 M mutation (P-value = 0.040). The presence of de novo T790 M has limitation in predicting disease progression by acquired T790 M, suggesting that identifying de novo T790 M through the ultrasensitive methods may not be necessary identifying patients who would be beneficial by 3rd-generation EGFR-TKI as the 1st line treatment. [ABSTRACT FROM AUTHOR]

The present study aimed to develop the sustained-release oral dosage form of pelubiprofen (PEL) by using the blended mixture of 3-aminopropyl functionalized-magnesium phyllosilicate (aminoclay) and pH-independent polymers. The sustained-release solid dispersion (SRSD) was prepared by the solvent evaporation method and the optimal composition of SRSD was determined as the weight ratio of drug: Eudragit® RL PO: Eudragit® RS PO of 1:1:2 in the presence of 1% of aminoclay (SRSD(F6)). The dissolution profiles of SRSD(F6) were examined at different pHs and in the simulated intestinal fluids. The drug release from SRSD(F6) was limited at pH 1.2 and gradually increased at pH 6.8, resulting in the best fit to Higuchi equation. The sustained drug release from SRSD(F6) was also maintained in simulated intestinal fluid at fasted-state (FaSSIF) and fed-state (FeSSIF). The structural characteristics of SRSD(F6) were examined by using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), indicating the change of drug crystallinity to an amorphous form. After oral administration in rats, SRSD(F6) exhibited the prolonged drug exposure in plasma. For both PEL and PEL-transOH (active metabolite), once a day dosing of SRSD(F6) achieved oral exposure (AUC) comparable to those from the multiple dosing (3 times a day) of untreated drug. In addition, thein vivoabsorption of SRSD(F6) was well-correlated with thein vitrodissolution data, establishing a good level Ain vitro/in vivocorrelation. These results suggest that SRSD(F6) should be promising for the sustained-release of PEL, thereby reducing the dosing frequency. [ABSTRACT FROM AUTHOR]