Baseline neutrophil-to-lymphocyte ratio predicts survival time after the initiation of nintedanib in patients with interstitial lung disease.

Double strand breaks induced by genotoxic agents, if inappropriately repaired, will cause cell death or induce cancer. Poly(ADP-ribose) polymerase-3 (PARP-3) serves a role in double strand break repair, and may be involved in tumorigenesis. To the best of our knowledge, the role of PARP-3 in breast cancer has not yet been examined. In the present study, the expression of PARP-3 was investigated in 493 breast cancer samples and 54 tumor-adjacent control samples using tissue-microarray-based immunohistochemistry. PARP-3 expression was higher in breast cancer samples compared with control samples. PARP-3 overexpression was significantly associated with histological grade II–III (P=0.012). In addition, PARP-3 overexpression was significantly associated with shorter disease-free survival (DFS; P=0.027) time and exhibited a tendency toward shorter overall survival (OS; P=0.183) time in patients with breast cancer compared with patients with lower PARP-3 expression, particularly in BRCA1-positive patients (P=0.004 for disease-free survival and P=0.095 for OS). Multivariate Cox regression analysis indicated that PARP-3 was an independent prognostic factor in patients with breast cancer. Furthermore, it was revealed that PARP-3 overexpression was associated with shorter survival time in patients with cyclophosphamide/doxorubicin or epirubicin/5-fluorouracil (CAF/CEF) chemotherapy compared with low PARP-3 expression, but not in patients with CAF/CEF + docetaxel chemotherapy. The present study suggested that PARP-3 may be used as a biomarker for predicting the clinical outcome of patients receiving chemotherapy, and targeting PARP-3 may be a potential therapeutic strategy for the treatment of breast cancer.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a poor prognosis. Nintedanib, an antifibrotic agent, has been shown in clinical trials to slow the decline in forced vital capacity (FVC) and reduce acute exacerbations (AE-IPF). Long-term studies confirm its continued effectiveness, though side effects like diarrhea may affect adherence. Despite real-world data supporting nintedanib's benefits, no prospective study has assessed its efficacy in early-stage IPF. This study evaluated the efficacy, safety, and tolerability of nintedanib in patients with early-stage IPF to assess its effectiveness outside randomized control trials. A 1-year interim analysis of a prospective, multicenter observational study was conducted in Kyushu and Okinawa, Japan. This study included 215 patients with early-stage IPF (stage I/II per the Japanese IPF severity system) who were followed up for 52 weeks. Changes in FVC and diffusion capacity of carbon monoxide (DLco); incidence of adverse events, acute exacerbations, and death; and factors associated with FVC decline and nintedanib discontinuation were evaluated. The percentage of predicted FVC (%FVC) remained stable, from 83.2% at baseline to 83.7% at 52 weeks, while %DLco decreased from 70.8% to 64.2%. Incidences of acute exacerbation and death were both 4.7%. Nintedanib was discontinued due to adverse events in 21.9% of the patients. Risk factors for FVC decline (>5%) included female sex, GAP stage II/III, low oxygen saturation (SpO2) in the 6-minute walk test (6 MWT), and elevated biomarkers (KL-6). Significant factors for nintedanib discontinuation were advanced age, modified Medical Research Council (mMRC) grade I or higher, GAP stage II/III, low %FVC, low SpO2 in the 6 MWT, short 6 MWT distance, and low albumin levels. The findings of this interim analysis indicate that nintedanib has good efficacy, safety, and tolerability for early-stage IPF in real-world settings, outside randomized control trials.

IntroductionIdiopathic pulmonary fibrosis (IPF) is the classic progressive fibrosing interstitial lung disease (ILD), but some patients with ILDs other than IPF also develop a progressive fibrosing phenotype (PF-ILD). Information on use and cost of healthcare resources in patients with PF-ILD is limited.MethodsWe used USA-based medical insurance claims (2014–2016) to assess use and cost of healthcare resources in PF-ILD. Patients with at least two ILD claims and at least one pulmonologist visit were considered to have ILD. Pulmonologist visit frequency was used as a proxy to identify PF-ILD (at least four visits in 2016, or at least three more visits in 2016 vs. 2014).ResultsOf 2517 patients with non-IPF ILD, 15% (n = 373) had PF-ILD. Mean annual medical costs associated with ILD claims were $35,364 in patients with non-IPF PF-ILD versus $20,211 in the non-IPF ILD population. In 2016, patients with non-IPF PF-ILD made more hospital ILD claims than patients with non-IPF ILD (10.5 vs. 4.7).ConclusionsThese findings suggest higher disease severity and overall healthcare use for patients with a non-IPF ILD manifesting a progressive fibrosing phenotype (non-IPF PF-ILD).Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01380-4) contains supplementary material, which is available to authorized users.

BackgroundSupplemental oxygen therapy is commonly prescribed in clinical practice for patients with fibrosing interstitial lung disease (ILD) to reduce breathlessness and increase physical capacity. Only a few studies have evaluated the incidence of oxygen therapy use, with evidence lacking in its use among fibrosing ILD subtypes including patients with idiopathic pulmonary fibrosis (IPF) and non-IPF ILD. This study aimed to estimate incidence of oxygen therapy and factors associated with oxygen therapy initiation.MethodsThis non-interventional study used US administrative claims and electronic health record data from 01 October 2015 to 30 June 2022. Patients aged ≥ 18 years with newly diagnosed fibrosing ILD (≥ 2 fibrosing ILD diagnoses in any position on different dates of service within 365 days) were included; the index date was the first date with ILD diagnosis. Patients were followed until the earlier of health plan disenrollment, death, or end of study period. Oxygen therapy use was evaluated among patients without evidence of oxygen therapy before the index date, stratified by the underlying fibrosing disease (i.e., IPF vs. non-IPF ILD). Factors associated with oxygen therapy use were evaluated using Cox proportional hazards regression.ResultsA total of 114,921 patients (IPF n = 5,555; non-IPF ILD n = 109,366) newly diagnosed with fibrosing ILD were included in the study. The mean (standard deviation) age of patients with ILD was 66.9 (14.2) years, and 47.2% were male. Patients were followed for a mean of 24 months after ILD diagnosis, during which 38% of fibrosing ILD patients initiated oxygen therapy; a higher proportion of patients with IPF initiated oxygen therapy compared to those with non-IPF ILD (68% and 36%, respectively). Factors associated with oxygen therapy initiation included IPF, higher Charlson comorbidity scores, and comorbidities that impair respiratory capacity.ConclusionsThe study findings demonstrate a substantial proportion of patients with fibrosing ILD initiated oxygen therapy following initial ILD diagnosis, with higher rates of oxygen therapy initiation observed among patients with IPF compared with non-IPF ILD. Respiratory comorbidities were key factors associated with increased initiation of oxygen therapy.

Neutrophil to Lymphocyte Ratio in Castration-Resistant Prostate Cancer Patients Treated With Daily Oral Corticosteroids.

PurposeThe differential diagnosis of interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF) versus other non-IPF ILDs, is important for selecting the appropriate treatment. This retrospective study aimed to explore the utility of gremlin-1 for the differential diagnosis.MethodsSerum gremlin-1 concentrations were measured using an ELISA in 50 patients with IPF, 42 patients with non-IPF ILD, and 30 healthy controls. The baseline clinical data, including pulmonary functions, prognosis, and three serum biomarkers (Krebs von den Lungen-6 [KL6], surfactant protein-D [SP-D], and lactate dehydrogenase [LDH]), were obtained through a medical record review for analyzing their associations with serum gremlin-1 concentrations. To evaluate the origin of gremlin-1, we performed immunostaining on lung sections.ResultsSerum gremlin-1 concentrations were significantly higher in patients with IPF (mean concentration, 14.4 ng/mL), followed by those with non-IPF ILD (8.8 ng/mL) and healthy controls (1.6 ng/mL). The area under the curve for IPF versus non-IPF ILDs was 0.759 (95% confidence interval, 0.661–0.857), which was superior to that of KL6/SP-D/LDH. The sensitivity and specificity for gremlin-1 (cutoff, 10.4 ng/mL) was 72 and 69%, respectively. By contrast, serum gremlin-1 concentrations were not associated with the pulmonary functions nor the prognosis in all patients with ILDs. In immunostaining, the gremlin-1 was broadly upregulated in IPF lungs, particularly at myofibroblasts, bronchiolar/alveolar epithelium, and CD163-positive M2-like macrophages.ConclusionsGremlin-1 may be a useful biomarker to improve the diagnostic accuracy for IPF compared to non-IPF ILDs, suggesting a role of this molecule in the pathogenesis of IPF.

Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial

POSITIVE ENVISIA GENOMIC CLASSIFIER RESULT PREDICTS CLINICAL PROGRESSION IN FIBROTIC INTERSTITIAL LUNG DISEASE

Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort study

Family History of Pulmonary Fibrosis Predicts Worse Survival in Patients With Interstitial Lung Disease

Real-world evidence on hospitalization, infection, and vascular outcomes among interstitial lung disease subtypes.

Progressive fibrosing interstitial lung diseases (ILDs) involve similar pathophysiological processes, indicating the potential for common approaches to treatment. Nintedanib (Ofev®), an intracellular tyrosine kinase inhibitor (TKI) with antifibrotic properties, was one of the first drugs approved for use in idiopathic pulmonary fibrosis (IPF) and has more recently been approved for use in other chronic fibrosing ILDs with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). In multinational phase III trials, nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) in adults with IPF, other progressive fibrosing ILDs and SSc-ILD. Reductions in FVC decline with nintedanib in patients with IPF and severe gas exchange impairment were comparable to those in patients with milder disease. Real-world experience in patients with IPF supports the effectiveness of nintedanib in slowing ILD progression. Nintedanib had a manageable tolerability profile in patients with fibrotic ILDs in clinical trials and real-world studies. No new safety signals have emerged from global pharmacovigilance data. Nintedanib continues to represent an important therapeutic option in patients with IPF and is the first drug to be approved for use in patients with other chronic fibrosing ILDs with a progressive phenotype or SSc-ILD, with these approvals expanding the range of fibrotic ILDs for which nintedanib can be prescribed.

Inflammatory markers as prognostic factors in metastatic castration-resistant prostate cancer

Marcadores inflamatorios como factor pronóstico en el cáncer de próstata resistente a la castración metastásico

Baseline Lung Function Had No Effect on Long-Term Reduction in FVC Decline With Nintedanib in Patients With Idiopathic Pulmonary Fibrosis (IPF)