Thoracic Operations for Pulmonary Nodules Are Frequently Not Futile in Patients with Benign Disease

IntroductionPulmonary nodules often require operative resection to obtain a diagnosis. However, 10 to 30% of operations result in a benign diagnosis. Our purpose was to determine whether negative thoracic operations are futile by describing the pathological diagnoses; determining new diagnoses and treatment changes initiated based on operative findings; and assessing morbidity, mortality, and cost of the procedure.MethodsAt our academic medical center, 278 thoracic operations were performed for known or suspected cancer between January 1, 2005, and April 1, 2009. We collected and summarized data pertaining to preoperative patient and nodule characteristics, pathologic diagnosis, postoperative treatment changes resulting from surgical resection, perioperative morbidity and mortality, and hospital charges for patients with benign pathology.ResultsTwenty-three percent (65/278) of patients who underwent surgical resection for a suspicious nodule had benign pathology. We report granulomatous disease in 57%, benign tumors in 15%, fibrosis in 12%, and autoimmune and vascular diseases in 9%. Definitive diagnosis or treatment changes occurred in 85% of cases. Surgical intervention led to a new diagnosis in 69%, treatment course changes in 68% of benign cases, medication changes in 38%, new consultation in 31%, definitive treatment in 9%, and underlying disease management in 34%. There was no intraoperative, in-hospital, or 30-day mortality. Postoperative in-hospital events occurred in seven patients. The mean total cost was $25,515 with a mean cost per day of$7618.ConclusionsPatients with a benign diagnosis after surgical resection for a pulmonary nodule received a new diagnosis or had a treatment course change in 85% of the cases

Development of automated brightfield double In Situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) for breast carcinomas and an assay performance comparison to manual dual color HER2 fluorescence In Situ hybridization (FISH)

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) fluorescence in situ hybridization (FISH) is a quantitative assay for selecting breast cancer patients for trastuzumab therapy. However, current HER2 FISH procedures are labor intensive, manual methods that require skilled technologists and specialized fluorescence microscopy. Furthermore, FISH slides cannot be archived for long term storage and review. Our objective was to develop an automated brightfield double in situ hybridization (BDISH) application for HER2 gene and chromosome 17 centromere (CEN 17) and test the assay performance with dual color HER2 FISH evaluated breast carcinomas. METHODS: The BDISH assay was developed with the nick translated dinitrophenyl (DNP)-labeled HER2 DNA probe and DNP-labeled CEN 17 oligoprobe on the Ventana BenchMark(® )XT slide processing system. Detection of HER2 and CEN 17 signals was accomplished with the silver acetate, hydroquinone, and H(2)O(2 )reaction with horseradish peroxidase (HRP) and the fast red and naphthol phosphate reaction with alkaline phosphatise (AP), respectively. The BDISH specificity was optimized with formalin-fixed, paraffin-embedded xenograft tumors, MCF7 (non-amplified HER2 gene) and BT-474 (amplified HER2 gene). Then, the BDISH performance was evaluated with 94 routinely processed breast cancer tissues. Interpretation of HER2 and CEN 17 BDISH slides was conducted by 4 observers using a conventional brightfield microscope without oil immersion objectives. RESULTS: Sequential hybridization and signal detection for HER2 and CEN 17 ISH demonstrated both DNA targets in the same cells. HER2 signals were visualized as discrete black metallic silver dots while CEN 17 signals were detected as slightly larger red dots. Our study demonstrated a high consensus concordance between HER2 FISH and BDISH results of clinical breast carcinoma cases based on the historical scoring method (98.9%, Simple Kappa = 0.9736, 95% CI = 0.9222 – 1.0000) and the ASCO/CAP scoring method with the FISH equivocal cases (95.7%, Simple Kappa = 0.8993%, 95% CI = 0.8068 – 0.9919) and without the FISH equivocal cases (100%, Simple Kappa = 1.0000%, 95% CI = 1.0000 – 1.0000). CONCLUSION: Automated BDISH applications for HER2 and CEN 17 targets were successfully developed and it might be able to replace manual two-color HER2 FISH methods. The application also has the potential to be used for other gene targets. The use of BDISH technology allows the simultaneous analyses of two DNA targets within the context of tissue morphological observation

Preoperative Cardiac Variables of Diastolic Dysfunction and Clinical Outcomes in Lung Transplant Recipients

Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP) and echocardiographic variables of diastolic dysfunction including mitral A>E and A′>E′. Results. Out of 111 patients, 62 were male (56%) and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A′>E′ and A>E, did not predict adverse events (P=0.49). Mildly elevated pretransplant PCWP (16–20 mmHg) and moderately/severely elevated PCWP (>20 mmHg) were not associated with adverse clinical events after transplant (P=0.30). Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events

Integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre for DNA probe immobilization

In this paper, we demonstrate the integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre (HC-PCF). In addition, we also show the fluorescence of Cy5-labelled DNA molecules immobilized within the hydrogel formed in two different types of HC-PCF. The 3D hydrogel matrix is designed to bind with the amino groups of biomolecules using an appropriate cross-linker, providing higher sensitivity and selectivity than the standard 2D coverage, enabling a greater number of probe molecules to be available per unit area. The HC-PCFs, on the other hand, can be designed to maximize the capture of fluorescence to improve sensitivity and provide longer interaction lengths. This could enable the development of fibre-based point-of-care and remote systems, where the enhanced sensitivity would relax the constraints placed on sources and detectors. In this paper, we will discuss the formation of such polyethylene glycol diacrylate (PEGDA) hydrogels within a HC-PCF, including their optical properties such as light propagation and auto-fluorescence

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey)

Background Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. Objectives The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. Methods Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). Results U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. Conclusions In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745

Variation in Soil Respiration across Soil and Vegetation Types in an Alpine Valley.

BACKGROUND AND AIMS: Soils of mountain regions and their associated plant communities are highly diverse over short spatial scales due to the heterogeneity of geological substrates and highly dynamic geomorphic processes. The consequences of this heterogeneity for biogeochemical transfers, however, remain poorly documented. The objective of this study was to quantify the variability of soil-surface carbon dioxide efflux, known as soil respiration (Rs), across soil and vegetation types in an Alpine valley. To this aim, we measured Rs rates during the peak and late growing season (July-October) in 48 plots located in pastoral areas of a small valley of the Swiss Alps. FINDINGS: Four herbaceous vegetation types were identified, three corresponding to different stages of primary succession (Petasition paradoxi in pioneer conditions, Seslerion in more advanced stages and Poion alpinae replacing the climactic forests), as well as one (Rumicion alpinae) corresponding to eutrophic grasslands in intensively grazed areas. Soils were developed on calcareous alluvial and colluvial fan deposits and were classified into six types including three Fluvisols grades and three Cambisols grades. Plant and soil types had a high level of co-occurrence. The strongest predictor of Rs was soil temperature, yet we detected additional explanatory power of sampling month, showing that temporal variation was not entirely reducible to variations in temperature. Vegetation and soil types were also major determinants of Rs. During the warmest month (August), Rs rates varied by over a factor three between soil and vegetation types, ranging from 2.5 μmol m-2 s-1 in pioneer environments (Petasition on Very Young Fluvisols) to 8.5 μmol m-2 s-1 in differentiated soils supporting nitrophilous species (Rumicion on Calcaric Cambisols). CONCLUSIONS: Overall, this study provides quantitative estimates of spatial and temporal variability in Rs in the mountain environment, and demonstrates that estimations of soil carbon efflux at the watershed scale in complex geomorphic terrain have to account for soil and vegetation heterogeneity

Growth rings show limited evidence for ungulates' potential to suppress shrubs across the Arctic

Global warming has pronounced effects on tundra vegetation, and rising mean temperatures increase plant growth potential across the Arctic biome. Herbivores may counteract the warming impacts by reducing plant growth, but the strength of this effect may depend on prevailing regional climatic conditions. To study how ungulates interact with temperature to influence growth of tundra shrubs across the Arctic tundra biome, we assembled dendroecological data from 20 sites, comprising 1153 individual shrubs and 223 63 annual growth rings. Evidence for ungulates suppressing shrub radial growth was only observed at intermediate summer temperatures (6.5 degrees C-9 degrees C), and even at these temperatures the effect was not strong. Multiple factors, including forage preferences and landscape use by the ungulates, and favourable climatic conditions enabling effective compensatory growth of shrubs, may weaken the effects of ungulates on shrubs, possibly explaining the weakness of observed ungulate effects. Earlier local studies have shown that ungulates may counteract the impacts of warming on tundra shrub growth, but we demonstrate that ungulates' potential to suppress shrub radial growth is not always evident, and may be limited to certain climatic conditions

Growth rings show limited evidence for ungulates’ potential to suppress shrubs across the Arctic

Global warming has pronounced effects on tundra vegetation, and rising mean temperatures increase plant growth potential across the Arctic biome. Herbivores may counteract the warming impacts by reducing plant growth, but the strength of this effect may depend on prevailing regional climatic conditions. To study how ungulates interact with temperature to influence growth of tundra shrubs across the Arctic tundra biome, we assembled dendroecological data from 20 sites, comprising 1153 individual shrubs and 223 63 annual growth rings. Evidence for ungulates suppressing shrub radial growth was only observed at intermediate summer temperatures (6.5 ◦C–9 ◦C), and even at these temperatures the effect was not strong. Multiple factors, including forage preferences and landscape use by the ungulates, and favourable climatic conditions enabling effective compensatory growth of shrubs, may weaken the effects of ungulates on shrubs, possibly explaining the weakness of observed ungulate effects. Earlier local studies have shown that ungulates may counteract the impacts of warming on tundra shrub growth, but we demonstrate that ungulates’ potential to suppress shrub radial growth is not always evident, and may be limited to certain climatic conditions.Research Council of Norwayhttp://iopscience.iop.org/1748-9326dm2022Mammal Research InstituteZoology and Entomolog

Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.Peer reviewe