Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Evaluation and management of small renal masses: looking beyond the tumor margin

In an effort to preserve renal function, nephron-sparing approaches such as partial nephrectomy are now routinely performed for the treatment of small renal masses (SRMs). To date, several groups have studied the utility of examining the renal parenchyma contained beyond the tumor margin of partial nephrectomy specimens for histopathologic evidence of non-neoplastic disease processes. The diagnosis of progressive renal disease through the study of this tissue allows for early medical intervention with possible further preservation of renal function. In this review, we discuss the management of SRMs with an emphasis on the emerging role of evaluating tumor specimens for non-neoplastic pathologic abnormalities. We believe that the thorough study of tissue contained beyond the tumor margin of partial nephrectomy specimens is the next step in preserving renal function and improving survival for patients with SRMs

Molecular marker for predicting treatment response in advanced renal cell carcinoma: does the promise fulfill clinical need?

Renal cell carcinoma (RCC) is largely diagnosed incidentally on imaging taken for unrelated reasons. The management of localized lesions is primarily extirpative with excellent results. Treatment of advanced RCC has evolved over recent years with the use of targeted therapies such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and antibody-mediated therapies. The treatment response to these targeted therapies is highly variable, with no clear clinical method of identifying patients who will benefit from or not tolerate therapy. The field of molecular markers has evolved significantly in the last decade, with a multitude of markers identified that predict treatment response and drug toxicity. The following review critically evaluates those molecular markers that have been assessed for their utility in predicting treatment response in patients with advanced/metastatic renal cell carcinoma (mRCC). Identifying the ideal treatment for these patients will improve responses to therapy, minimize morbidity, and save significant healthcare dollars

Colle chirurgicale OMNEX dans la réparation extracorporelle des anévrysmes de l'artère rénale

OMNEX (Ethicon, Inc. ; Somerville, NJ, USA) est une colle chirurgicale synthétique de cyanoacrylate. Jusqu'ici, l'utilisation d'OMNEX a été seulement décrite dans un nombre limité de procédures de chirurgie vasculaire. Nous présentons les cas de deux malades qui ont eu la cure extracorporelle réussie d'anévrysmes de l'artère rénale à l'aide de la colle OMNEX. Ce rapport est la première démonstration de l'utilité d'OMNEX en chirurgie réno-vasculaire

OMNEX Surgical Sealant in the Extracorporeal Repair of Renal Artery Aneurysms

OMNEX (Ethicon, Inc.; Somerville, NJ) is a cyanoacrylate-based synthetic surgical sealant. To date, the use of OMNEX has only been described in a limited number of vascular surgery procedures. We present the cases of two patients who underwent successful extracorporeal renal artery aneurysm repair with the aid of OMNEX sealant. This report is the first evidence to suggest the utility of OMNEX in renovascular surgery

Inferior vena cava resection and reconstruction: technical considerations in the surgical management of renal cell carcinoma with tumor thrombus

The mainstay of treatment for renal cell carcinoma with invasion of the inferior vena cava (IVC) is complete surgical extirpation. Cases complicated by adherent or invasive tumor thrombus represent a special technical challenge due to the need for resection of a large segment of the IVC. The aim of this review is to describe the indications and surgical approach for radical nephrectomy with en bloc resection of the IVC with or without venous reconstruction. In addition, special attention is paid to the relevant anatomical and hemodynamic considerations related to the development of venous collateral pathways secondary to IVC obstruction

Transplantation techniques for the resection of renal cell carcinoma with tumor thrombus: a technical description and review

Renal cell carcinoma with tumor thrombus of the inferior vena cava presents a special surgical challenge. The use of surgical techniques derived from the field of transplantation surgery have previously been shown to enable optimal control of inferior vena cava, allowing for the extirpation of most tumors via a transabdominal approach without the need for venovenous or cardiopulmonary bypass. In this report, we provide a stepwise description of the transplantation techniques employed at the University of Miami/Jackson Memorial Hospital for the resection of renal cell carcinoma with intracaval tumor. In addition, we review the results of centers that have utilized these surgical maneuvers