Hydrogen sulfide (H(2)S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H(2)S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 microM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H(2)S gas and turnover of exogenous H(2)S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H(2)S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H(2)S could transiently increase, we measured oxygen-dependent H(2)S production by trout hearts in vitro and in vivo. H(2)S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H(2)S production was inversely related to Po(2), whereas we failed to detect H(2)S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H(2)S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H(2)S signaling is mediated by the circulation.

Background Fluoro-deoxyglucose positron emission tomography (FDG-PET) is recommended for diagnosis and staging of NSCLC. Meta-analyses of FDG-PET diagnostic accuracy demonstrated sensitivity and specificity of 96% and 78%, respectively but were performed in select centers introducing potential bias. This study evaluates the accuracy of FDG-PET to diagnose NSCLC and examines differences across enrolling sites in the national ACOSOG Z4031 trial. Methods 959 eligible patients with clinical stage I (cT1-2N0M0) known or suspected NSCLC were enrolled between 2004 and 2006 in the Z4031 trial and 682 had a baseline FDG-PET. Final diagnosis was determined by pathological examination. FDG-PET avidity was categorized into four levels based on radiologist description or reported maximum standard uptake value (SUV). FDG-PET diagnostic accuracy was calculated for the entire cohort. Accuracy differences based on preoperative size and by enrolling site were examined. Results Preoperative FDG-PET results were available for 682 participants enrolled at 51 sites in 39 cities. Lung cancer prevalence was 83%. FDG-PET sensitivity was 82% (95% CI: 79–85) and specificity was 31% (95% CI: 23%–40%). Positive and negative predictive values were 85% and 26%, respectively. Accuracy improved with lesion size. Of 80 false positive scans, 69% were granulomas. False negative scans occurred in 101 patients with adenocarcinoma being the most frequent (64%) and eleven were ≤10mm. The sensitivity varied from 68% to 91% (p=0.03) and the specificity ranged from 15% to 44% (p=0.72) across cities with > 25 participants. Conclusions In a national surgical population with clinical stage I NSCLC, FDG-PET to diagnose lung cancer performed poorly compared to published studies.

Background Breast cancer incidence and mortality are influenced by early-detection methods, including mammographic screening. Demographic changes in US statistics serve as a model for changes that can be anticipated in countries where mammographic screening has not been implemented. Methods SEER statistics (1973–2013) for breast cancer mortality, incidence, stage at diagnosis, and age at diagnosis were examined. Temporal associations between screening changes and breast cancer demographics in the US were documented. Findings Before 1982 (pre-screening), breast cancer incidence in the US remained stable, with similar incidence of localized and regional cancers, and with in-situ disease comprising <2% of diagnosed disease1. During the transitional phase of mammographic screening, breast cancer incidence increased. In 1991, breast cancer age-adjusted mortality rates began decreasing and have continued to decrease. In the post-screening phase, stage distribution stabilized, but now with localized and in-situ disease representing the majority of diagnosed cases. The median age at diagnosis has increased to 61 years. Discussion Mammographic screening increases breast cancer incidence, shifts the stage distribution toward earlier stage disease, and, in high-income countries, is associated with improved survival. Whether similar improvement in breast cancer survival can be achieved in the absence of mammographic screening has yet to be conclusively demonstrated.

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Background: Despite promising pilot study results, adoption of neurotization of immediate implant-based reconstructions has not occurred. Methods: For surgeons interested in adopting breast reinnervation techniques, we present ways to overcome initial barriers by decreasing operative time and maximizing chances of sensory recovery. Results: We discuss the combined experience at two academic teaching hospitals, where neurotization of both immediate tissue expander cases and direct-to-implant reconstructions are performed through varying mastectomy incisions. Conclusion: Initial barriers can be overcome by shortening operative time and providing an individualized reinnervation approach that aims to increase the chance of meaningful sensation.