The aim of this study was to examine the hypothesis that alveolar macrophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Release of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. Increased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macrophages. With gelatinase B, complexed forms of the enzyme were secreted by patient but not by control macrophages. No difference in transcript levels of gelatinase A or MME was observed between patient and control samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alveolar macrophages from the emphysematous lung produce elevated quantities of matrix-degrading enzymes with both elastolytic and collagenolytic activities.

Background: In the phase 3 IMpassion130 trial, combining atezo with first-line nabpaclitaxel for mTNBC showed significantly improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit in patients with PD-L1+ mTNBC [Schmid NEJM 2018]. IMpassion131 (NCT03125902) evaluated atezo + PAC as firstline treatment for mTNBC. a Unconfirmed abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S1147

OBJECTIVE The purpose of this trial was to compare usual patient education plus the Internet-based, Personal Patient Profile-Prostate, versus usual education alone, on conflict associated with decision making, plus explore time-to-treatment and treatment choice. METHODS A randomized, multi-center clinical trial was conducted with measures at baseline, one and six months. Men with newly diagnosed localized prostate cancer who sought consultation at urology, radiation oncology or multi-disciplinary clinics in four geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using Generalized Estimating Equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice and program acceptability/usefulness, were explored. RESULTS A total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time as compared with the control group, for the uncertainty score (estimate −3.61; (confidence interval, −7.01,−0.22) and values clarity (estimate −3.57; confidence interval (−5.85,−1.30) Borderline effect was seen for the total decisional conflict score (estimate −1.75; confidence interval (−3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated. CONCLUSION The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized prostate cancer. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a prostate cancer treatment that is consistent with the patient values and preferences.

Pulmonary emphysema is a condition of the lung characterised by progressive destruction Background -Matrix degradation in emand loss of functioning alveoli. The mechphysema has long been attributed to the anisms involved in extracellular matrix (ECM) action of neutrophil elastase (NE). More damage are not precisely known but a sigrecently a role for other proteases, parnificant body of evidence supports the proteaseticularly the matrix metalloproteinases antiprotease theory which postulates that an (MMPs), in the pathogenesis of this disexcess of proteolytic activity over the inhibitory ease has been proposed. To date, however, capacity of the lung leads to parenchymal dethe presence of MMPs in the lungs of struction. 1 Most studies to date have focused patients with emphysema has not been on the role of neutrophil elastase (NE) as the demonstrated.major effector protease involved. 2 More reMethods -Samples of bronchoalveolar cently, however, there has been considerable lavage (BAL) fluid from 10 patients with speculation on the potential involvement of emphysema and from control subjects other proteases, particularly the matrix metallomatched for sex and current smoking proteinases (MMPs), in matrix degradation in status were assessed for collagenase, emphysema.3 gelatinase, and NE activity. PulmonaryThe MMPs are a highly homologous family function tests and computed tomographic of endopeptidases which are collectively cap-(CT) scans were carried out on all study able of breaking down all the constituents of subjects.the alveolar ECM, including collagen, elastin, Results -Collagenase activity was detected proteoglycans, laminin, and fibronectin.4 They in BAL fluid samples from all em-are produced by a range of stromal cells and physematous patients but in only one by two of the major inflammatory cells imsmoking control (p<0.001). Gelatinase B plicated in emphysema -the alveolar macrowas present in six patients and in two phage and the neutrophil. Indirect evidence smoking controls (p<0.03). The con-that MMPs may play a part in tissue destruction comitant presence of gelatinase B in in emphysema comes from a number of studies. complex with lipocalin (NGAL) in the gel-Janoff et al demonstrated that the elastolytic atinase positive samples suggests that the activity of bronchoalveolar lavage (BAL) fluid neutrophil is a significant source of the from smokers was significantly inhibited by gelatinase B observed. NE was detected in metal chelating agents and concluded that