Greenslopes Private Hospital

About: Greenslopes Private Hospital is a healthcare organization based out in Brisbane, Queensland, Australia. It is known for research contribution in the topics: Population & Catheter ablation. The organization has 345 authors who have published 430 publications receiving 8872 citations.

The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study

Abstract: A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria (NTM) isolation worldwide. To provide a snapshot of NTM species distribution, global partners in the NTM-Network European Trials Group (NET) framework (www.ntm-net.org), a branch of the Tuberculosis Network European Trials Group (TB-NET), provided identification results of the total number of patients in 2008 in whom NTM were isolated from pulmonary samples. From these data, we visualised the relative distribution of the different NTM found per continent and per country. We received species identification data for 20 182 patients, from 62 laboratories in 30 countries across six continents. 91 different NTM species were isolated. Mycobacterium avium complex (MAC) bacteria predominated in most countries, followed by M. gordonae and M. xenopi. Important differences in geographical distribution of MAC species as well as M. xenopi, M. kansasii and rapid-growing mycobacteria were observed. This snapshot demonstrates that the species distribution among NTM isolates from pulmonary specimens in the year 2008 differed by continent and differed by country within these continents. These differences in species distribution may partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.

Adrenal vein sampling: how to make it quick, easy, and successful.

Abstract: Adrenal vein sampling has a reputation as a difficult procedure. However, it is being performed more frequently at some institutions due to the realization that primary aldosteronism is more common than previously believed. At the author's institution, adrenal vein sampling with computed tomographic (CT) and laboratory correlation has been performed more than 800 times in the past 10 years. Adrenal vein sampling is used to determine whether autonomous hormone production is unilateral or bilateral; unilateral secretion can be treated with surgery. The venous drainage of each adrenal gland is predominantly via a central vein. Recognition of the right adrenal vein is the crux of adrenal vein sampling. CT is useful in planning adrenal vein sampling by demonstrating the anatomy and positions of the adrenal veins. A small amount of contrast material is injected gently and slowly into the adrenal vein; it is not necessary to perform formal venography to outline the entire gland. To confirm that the vein is draining the majority of adrenal cortical blood, the adrenal vein sample should have a significantly higher level of cortisol than a peripheral sample. Adrenal glands that are producing aldosterone demonstrate an aldosterone-cortisol ratio that is higher than the peripheral value.

Survival Outcomes in Patients With Previously Untreated BRAF Wild-Type Advanced Melanoma Treated With Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial

Abstract: Importance This analysis provides long-term follow-up in patients withBRAFwild-type advanced melanoma receiving first-line therapy based on anti–programmed cell death 1 receptor inhibitors. Objective To compare the 3-year survival with nivolumab vs that with dacarbazine in patients with previously untreatedBRAFwild-type advanced melanoma. Design, Setting, and Participants This follow-up of a randomized phase 3 trial analyzed 3-year overall survival data from the randomized, controlled, double-blind CheckMate 066 phase 3 clinical trial. For this ongoing, multicenter academic institution trial, patients were enrolled from January 2013 through February 2014. Eligible patients were 18 years or older with confirmed unresectable previously untreated stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 but without aBRAFmutation. Interventions Patients were treated until progression or unacceptable toxic events with nivolumab (3 mg/kg every 2 weeks plus dacarbazine-matched placebo every 3 weeks) or dacarbazine (1000 mg/m2every 3 weeks plus nivolumab-matched placebo every 2 weeks). Main Outcome and Measure Overall survival. Results At minimum follow-ups of 38.4 months among 210 participants in the nivolumab group (median age, 64 years [range, 18-86 years]; 57.6% male) and 38.5 months among 208 participants in the dacarbazine group (median age, 66 years [range, 25-87 years]; 60.1% male), 3-year overall survival rates were 51.2% (95% CI, 44.1%-57.9%) and 21.6% (95% CI, 16.1%-27.6%), respectively. The median overall survival was 37.5 months (95% CI, 25.5 months–not reached) in the nivolumab group and 11.2 months (95% CI, 9.6-13.0 months) in the dacarbazine group (hazard ratio, 0.46; 95% CI, 0.36-0.59;P Conclusions and Relevance Nivolumab led to improved 3-year overall survival vs dacarbazine in patients with previously untreatedBRAFwild-type advanced melanoma. Trial Registration ClinicalTrials.gov identifier:NCT01721772

Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma.

Abstract: Oncogene-targeted therapy with B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in patients with BRAF V600-mutated melanoma, with a median duration of response of approximately 1 year 1–3 . Immunotherapy with antibodies to programmed death 1 (PD-1) produces lower response rates but with long response duration. Preclinical models suggest that combining BRAF and MEK inhibitors with PD-1 blockade therapy improves antitumor activity 4–6 , which may provide additional treatment options for patients unlikely to have long-lasting responses to either mode of therapy alone. We enrolled 15 patients with BRAF V600-mutated metastatic melanoma in a first-in-human clinical trial of dabrafenib, trametinib and pembrolizumab ( NCT02130466 ). Eleven patients (73%) experienced grade 3/4 treatment-related adverse events, the most common being elevation of liver function tests and pyrexia, most of which resolved with drug interruption or discontinuation of either the anti-PD-1 antibody or the targeted therapy combination. Eleven patients (73%; 95% confidence interval = 45–92%) had an objective response, and six (40%; 95% confidence interval = 16–68%) continued with a response at a median follow-up of 27 months (range = 10.3–38.4+ months) for all patients. This study suggests that this triple-combined therapy may benefit a subset of patients with BRAF V600-mutated metastatic melanoma by increasing the frequency of long-lasting antitumor responses. Triple therapy combining BRAF and MEK inhibitors with immune checkpoint blockade may benefit a subset of patients with BRAF V600-mutated metastatic melanoma.

Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma

Abstract: Blocking programmed death 1 (PD-1) may enhance the durability of anti-tumor responses that are induced by the combined inhibition of BRAF and MEK1. Here we performed a randomized phase 2 trial ( NCT02130466 ), in which patients with treatment-naive BRAFV600E/K-mutant, advanced melanoma received the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib together with the PD-1-blocking antibody pembrolizumab (triplet; n = 60) or placebo (doublet; n = 60). The primary end point of progression-free survival was numerically improved in the triplet group—16.0 months—compared with 10.3 months in the doublet group (hazard ratio, 0.66; P = 0.043); however, the trial did not reach the planned benefit for a statistically significant improvement. Median duration of response was 18.7 months (95% confidence interval, 10.1–22.1) and 12.5 months (95% confidence interval, 6.0–14.1); 59.8 and 27.8% of responses were estimated to have lasted for more than 18 months for triplet and doublet treatment, respectively. Grade 3–5 treatment-related adverse events occurred in 58.3 and 26.7% of patients treated with triplet and doublet therapies, respectively, which were most commonly fever, increased transaminase levels and rash. One patient who received triplet therapy died of pneumonitis. In summary, triplet therapy with dabrafenib, trametinib and pembrolizumab conferred numerically longer progression-free survival and duration of response with a higher rate of grade 3/4 adverse events compared with the doublet therapy of dabrafenib, trametinib and placebo. A randomized phase 2 trial testing triple combination of BRAF, MEK and PD-1 inhibition as first-line therapy in patients with BRAF-mutant melanoma shows durable responses and encouraging progression-free survival.