[F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer.

Background: Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αβ and αβ are both upregulated in tumor-associated vasculature.

OptiJ: Open-source optical projection tomography of large organ samples.

The three-dimensional imaging of mesoscopic samples with Optical Projection Tomography (OPT) has become a powerful tool for biomedical phenotyping studies. OPT uses visible light to visualize the 3D morphology of large transparent samples. To enable a wider application of OPT, we present OptiJ, a low-cost, fully open-source OPT system capable of imaging large transparent specimens up to 13 mm tall and 8 mm deep with 50 µm resolution.

Diffusion-weighted MRI in Advanced Epithelial Ovarian Cancer: Apparent Diffusion Coefficient as a Response Marker.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival.

Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions.

OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution.

Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS).

Background: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

Methods: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics.

Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study.

Background: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.

Methods: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016.

Glucagonoma-associated dilated cardiomyopathy refractory to somatostatin analogue therapy.

A 67-year-old woman presented with a generalised rash associated with weight loss and resting tachycardia. She had a recent diagnosis of diabetes mellitus. Biochemical evaluation revealed elevated levels of circulating glucagon and chromogranin B.

Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.

Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab.

Context: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumor syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that several cancers characterized by MMR deficiency are sensitive to immune checkpoint inhibitors that target PD-1.

Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-1-regulated apoptosis in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) progression and chemotherapy insensitivity have been associated with aberrant PI3K/mTOR/MEK signalling. However, cell death responses activated by inhibitors of these pathways can differ - contextually varying with tumour genetic background. Here, we demonstrate that combining the dual PI3K/mTOR inhibitor PF5212384 (PF384) and MEK inhibitor PD325901 (PD901) more effectively induces apoptosis compared with either agent alone, independent of KRAS mutational status in PDAC cell lines.

Imaging-based clusters in current smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Background: Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.

Methods: Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.

Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study.

Background: Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to enter the clinic and is designed to overcome these key resistance mechanisms.

Methods: Sixty-eight patients with advanced solid tumours who had relapsed after treatment with standard therapy were recruited to a dose escalation study to determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031.

Prognostic factors for first-line therapy and overall survival of metastatic uveal melanoma: The Princess Margaret Cancer Centre experience.

Metastatic uveal melanoma (MUM) has a poor prognosis, with no established standard of care. Delineation of prognostic factors in MUM patients may enable stratified treatment algorithms of stage-specific survival. Overall, 132 MUM patients who presented to a single tertiary institution in Toronto, Canada, over 12 years were identified and data (demographics, clinical status, radiographic images, and laboratory values) were extracted.

Characterisation of tumour microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact (an OCTIPS Consortium study).

Background: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature evolution remains unknown. The study investigated changes in tumour microvessel density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue samples and its impact on patients' clinico-pathological outcome.

Methods: A total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were assessed for immunohistochemical expression of angiogenesis-associated biomarkers (CD31, to evaluate MVD, and VEGF-A).

Peptidomic analysis of endogenous plasma peptides from patients with pancreatic neuroendocrine tumours.

Rationale: Diagnosis of pancreatic neuroendocrine tumours requires the study of patient plasma with multiple immunoassays, using multiple aliquots of plasma. The application of mass spectrometry based techniques could reduce the cost and amount of plasma required for diagnosis.

Methods: Plasma samples from two patients with pancreatic neuroendocrine tumours were extracted using an established acetonitrile-based plasma peptide enrichment strategy.

The development of AZD7624 for prevention of exacerbations in COPD: a randomized controlled trial.

Background: p38 mitogen-activated protein kinase (MAPK) plays a central role in the regulation and activation of pro-inflammatory mediators. COPD patients have increased levels of activated p38 MAPK, which correlate with increased lung function impairment, alveolar wall inflammation, and COPD exacerbations.

Objectives: These studies aimed to assess the effect of p38 inhibition with AZD7624 in healthy volunteers and patients with COPD.

Smoking duration alone provides stronger risk estimates of chronic obstructive pulmonary disease than pack-years.

Background: Cigarette smoking is the strongest risk factor for COPD. Smoking burden is frequently measured in pack-years, but the relative contribution of cigarettes smoked per day versus duration towards the development of structural lung disease, airflow obstruction and functional outcomes is not known.

Methods: We analysed cross-sectional data from a large multicentre cohort (COPDGene) of current and former smokers.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

Background: Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions.

Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

 To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions. An umbrella review of meta-analyses. PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome.

Deterioration of Limb Muscle Function during Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Important features of both stable and acute exacerbation of chronic obstructive pulmonary disease (COPD) are skeletal muscle weakness and wasting. Limb muscle dysfunction during an exacerbation has been linked to various adverse outcomes, including prolonged hospitalization, readmission, and mortality. The contributing factors leading to muscle dysfunction are similar to those seen in stable COPD: disuse, nutrition/energy balance, hypercapnia, hypoxemia, electrolyte derangements, inflammation, and drugs (i.

A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer.

Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing.

Erratum: Erratum: Efficacy of Formoterol Fumarate Delivered by Metered Dose Inhaler Using Co-Suspension™ Delivery Technology Versus Foradil® Aerolizer® in Moderate-To-Severe COPD: A Randomized, Dose-Ranging Study.

[This corrects the article DOI: 10.15326/jcopdf.4.

The 2017 Update to the COPD Foundation COPD Pocket Consultant Guide.

The COPD Foundation Pocket Consultant Guide (PCG) was first released in 2007 as a practice tool for use at point of service for clinicians, especially primary care clinicians diagnosing and treating patients with chronic obstructive pulmonary disease (COPD). Over the years, the PCG has been supplemented with a mobile app that presents the tool in an online smart phone accessible version that also allows the clinician to enter patient specific data for guidance to next steps of diagnosis or management. In November 2016, a new update of the PCG was released that incorporates a flow diagram for stepped care that includes the newest recommendation for diagnosis, assessment and treatment; including the broad use of dual bronchodilator therapy and consideration of asthma COPD overlap syndrome (ACOS).