Real-World Clinical Efficacy of Antifibrotic Agents for Idiopathic Pulmonary Fibrosis: A Single-Center Retrospective Study in Japan.

BACKGROUND: The antifibrotic drugs, nintedanib and pirfenidone, inhibit the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib also inhibits the onset of acute exacerbation and reduces the risk of all-cause mortality. However, their effectiveness in real-world practice remains unclear. Our study aimed to investigate the changes in forced vital capacity, survival period, causes of death, and risk factors for mortality in patients with IPF receiving antifibrotic drugs. METHODS: This retrospective study enrolled Japanese patients who visited Toho University Sakura Medical Center who were diagnosed with IPF and received antifibrotic drugs. RESULTS: We included 102 patients [mean age ± standard deviation (SD): 71.8 ± 7.5 years], of whom 76 were males. The decline in forced vital capacity (mean ± SD) during the antifibrotic therapy period was - 154 ± 259 mL/year, which was significantly lower than before the antifibrotic therapy period (- 484 ± 589 mL/year; n = 80, p = 0.003). Altogether, 52 deaths were confirmed, and the median survival time from antifibrotic therapy initiation was 38.0 months (95% confidence interval: 25.9-50.1 months). Acute exacerbation accounted for 9.6% of all deaths (95% confidence interval: 1.6-17.6). The decline in forced vital capacity during antifibrotic therapy was a risk factor for mortality. CONCLUSIONS: In actual clinical practice in Japan, antifibrotic drugs suppressed the gradual decline in forced vital capacity, which is a risk factor for mortality. However, the median survival period remained poor at 38 months.

A nationwide survey of adrenal incidentalomas in Japan: the first report of clinical and epidemiological features.

The aim of this study was to reveal clear epidemiologic and clinical characteristics of incidentally discovered adrenal masses, termed adrenal incidentalomas (AIs), and to establish appropriate managemental and therapeutic regimens in Japan. This study had been originally carried out as a project of a research proposed on behalf of the Japanese Ministry of Health, Labour and Welfare, from 1999 to 2004. This nationwide multicenter study on AIs included 3,672 cases with clinically diagnosed AIs, involving 1,874 males and 1,738 females, with mean age 58.1 ± 13.0 years (mean ± SD). In the present study, we focused on the investigation of the real prevalence of various adrenal disorders with AI. The mean nodule size of AI based on computed tomography was 3.0 ± 2.0 cm. Compared to non-functioning adenomas (NFAs), tumor diameters were significantly larger in adrenocortical carcinomas (ACCs), pheochromocytomas, cortisol-producing adenomas (CPAs), myelolipomas, metastatic tumors, cysts, and ganglioneuromas (p < 0.01). Endocrinological evaluations demonstrated that 50.8% of total AIs were non-functioning adenomas, while 10.5%, including 3.6% with subclinical Cushing's syndrome, were reported as CPAs, 8.5% as pheochromocytomas, and 5.1% as aldosterone-producing adenomas. ACCs were accounted for 1.4% (50 cases) among our series of AIs. In conclusion, while almost 50 % of AIs are non-functional adenomas, we must be particularly careful as AIs include pheochromocytomas or adrenal carcinomas, because they may be asymptomatic. To our knowledge, this is the first and the largest investigation of AI, thus providing basic information for the establishment of clinical guidelines for the management of AI.

Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study.

The Research Committee of Disorders of Adrenal Hormones, Japan, undertook a nationwide epidemiological study of primary aldosteronism (PA). The present study was undertaken as a part of this study to reveal the relationship between type of treatment and the prognosis of PA. In the primary survey, 4161 patients with PA during the period January 1, 2003-December 31, 2007 were reported from 3252 departments of internal medicine, pediatrics and urology. In the secondary survey, a questionnaire that requested detailed clinical information on individual patients was sent to those departments reporting patients in the primary survey. In total, data on 1706 patients with PA were available in the present study. Among patients with bilateral or unilateral aldosterone-producing adenoma, after adjustment for age at which prognosis was examined, sex, surgical treatment and medical treatment, surgical treatment was significantly associated with amelioration of hypertension (adjusted odds ratio [OR]: 0.47 [95% confidence interval (CI): 0.29-0.77]) and hypokalemia (adjusted OR: 0.17 [95% CI: 0.11-0.29]). No significant relationship was observed between medical treatment and such prognosis in this group of patients. Among patients with bilateral or unilateral adrenal hyperplasia, surgical, but not medical, treatment was significantly associated with amelioration of hypokalemia (adjusted OR: 0.23 [95% CI: 0.06-0.74]), while there was no relationship between surgical or medical treatment and the prognosis of hypertension. In conclusion, surgery offered a better prognosis of PA than medication with regards to hypertension and hypokalemia, with the limitation that a new anti-aldosterone drug, eplerenone, was not available during the study period.

Establishment and characterization of a novel cell line derived from a human small cell lung carcinoma that secretes parathyroid hormone, parathyroid hormone-related protein, and pro-opiomelanocortin.

There are few case reports describing small cell lung carcinoma (SCLC), which secrete parathyroid hormone (PTH)-related protein (PTHrP) and result in hypercalcemia. We have established a novel cell line, derived from a 37-year-old woman with SCLC, which produced PTH, PTH-rP, and a part of proopiomelanocortin (POMC), and led to hypercalcemia. The cell line, named SS-1, was grown as floating cell clusters in DMEM/F12 medium supplemented with 10% fetal bovine serum and had a population doubling time of 72 h. The modal chromosome number was 47 (88%); marker chromosomes were not observed. The SS-1 cell line secreted not only PTHrP but also PTH, and both were decreased by CaCl(2) administration. Decreasing the concentration of Ca(++) in the growth medium stimulated the secretion of both PTHrP and PTH. The cell line had calcium sensing receptor (Cas-R). Since PTHrP and PTH secretion from the SS-1 cells was related to Ca(++) concentration in the growth medium, the cell line might be useful for the study of PTH-rP and PTH regulation as well as for SCLC analysis. In addition, the cells secreted N terminal POMC, the precursor of adrenocorticotropic hormone, in response to stimulation with corticotropin releasing hormone. In summary, we established a novel cell line, SS-1 from SCLC, which produced PTHrP, PTH and N terminal POMC.