Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Unusual presentation of cactus spines in the flank of an elderly man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Splinters and spines of plant matter are common foreign bodies in skin wounds of the extremities, and often present embedded in the dermis or subcutaneous tissue. Vegetative foreign bodies are highly inflammatory and, if not completely removed, can cause infection, toxic reactions, or granuloma formation. Older patients are at increased risk for infection from untreated plant foreign bodies. The most common error in plant splinter and spine management is failure to detect their presence.</p> <p>Case presentation</p> <p>Here we report a case of cactus spines in an 84-year-old Caucasian man presenting on the right flank as multiple, red papules with spiny extensions. This presentation was unusual both in location and the spinous character of the lesions, and only after punch biopsy analysis was a diagnosis of cactus matter spines made.</p> <p>Conclusions</p> <p>Our patient presented with an unusual case of cactus spines that required histopathology for identification. Skin lesions with neglected foreign bodies are a common cause of malpractice claims. If not removed, foreign bodies of the skin, particularly in elderly individuals, can result in inflammatory and infectious sequela. This report underscores the importance of thoroughly evaluating penetrating skin lesions for the presence of foreign bodies, such as splinters and spines.</p

Technical and Clinical Outcome of Talent versus Endurant Endografts for Endovascular Aortic Aneurysm Repair

The technical evolution of endografts for the interventional management of infrarenal abdominal aortic aneurysms (AAA) has allowed a continuous expansion of indications. This study compares the established Talent endograft with its successor, the Endurant endograft, taking individual aortoiliac anatomy into account.From June 2007 to December 2010, 35 patients with AAA were treated with a Talent endograft (33 men) and 36 patients with an Endurant endograft (34 men). Aortoiliac anatomy was evaluated in detail using preinterventional computed tomography angiography. The 30-day outcome of both groups were compared regarding technical and clinical success as well as complications including endoleaks.The Endurant group included more patients with unfavorable anatomy (kinking of pelvic arteries, p = 0.017; shorter proximal neck, p = 0.084). Primary technical success was 91.4% in the Talent group and 100% in the Endurant group (p = 0.115). Type 1 endoleaks occurred in 5.7% of patients in the Talent group and in 2.8% of those in the Endurant group (p = 0.614). Type 3 endoleaks only occurred in the Talent group (2.9% of patients; p = 0.493). Type 2 endoleaks were significantly less common in the Endurant group than in the Talent group (8.3% versus 28.6%; p = 0.035). Rates of major and minor complications were not significantly different between both groups. Primary clinical success was significantly better in the Endurant group (97.2%) than in the Talent group (80.0%) (p = 0.028).Endurant endografts appear to have better technical and clinical outcome in patients with difficult aortoiliac anatomy, significantly reducing the occurrence of type 2 endoleaks

Nanotube Action between Human Mesothelial Cells Reveals Novel Aspects of Inflammatory Responses

A well-known role of human peritoneal mesothelial cells (HPMCs), the resident cells of the peritoneal cavity, is the generation of an immune response during peritonitis by activation of T-cells via antigen presentation. Recent findings have shown that intercellular nanotubes (NTs) mediate functional connectivity between various cell types including immune cells - such as T-cells, natural killer (NK) cells or macrophages - by facilitating a spectrum of long range cell-cell interactions. Although of medical interest, the relevance of NT-related findings for human medical conditions and treatment, e.g. in relation to inflammatory processes, remains elusive, particularly due to a lack of appropriate in vivo data. Here, we show for the first time that primary cultures of patient derived HPMCs are functionally connected via membranous nanotubes. NT formation appears to be actin cytoskeleton dependent, mediated by the action of filopodia. Importantly, significant variances in NT numbers between different donors as a consequence of pathophysiological alterations were observable. Furthermore, we show that TNF-α induces nanotube formation and demonstrate a strong correlation of NT connectivity in accordance with the cellular cholesterol level and distribution, pointing to a complex involvement of NTs in inflammatory processes with potential impact for clinical treatment

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.</p> <p>Methods</p> <p>6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.</p> <p>Results</p> <p>MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm³+/-243 mm³) with MRI (mean 918 mm³+/-193 mm³) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm²+/-22.8 mm²versus 32.6 mm²+/-22.6 mm²(histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm³+/-56.7 mm³after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.</p> <p>Conclusions</p> <p>This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.</p

Mass loss from hot massive stars

Mass loss is a key process in the evolution of massive stars, and must be understood quantitatively to be successfully included in broader astrophysical applications. In this review, we discuss various aspects of radiation driven mass loss, both from the theoretical and the observational side. We focus on winds from OB-stars, with some excursions to the Luminous Blue Variables, Wolf- Rayet stars, A-supergiants and Central Stars of Planetary Nebulae. After reca- pitulating the 1-D, stationary standard model of line-driven wind, extensions accounting for rotation and magnetic fields are discussed. The relevance of the so-called bi-stability jump is outlined. We summarize diagnostical methods to infer wind properties from observations, and compare the results with theore- tical predictions, featuring the massloss-metallicity dependence. Subsequently, we concentrate on two urgent problems which challenge our present understanding of radiation driven winds: weak winds and wind- clumping. We discuss problems of measuring mass-loss rates from weak winds and the potential of NIR- spectroscopy. Wind-clumping has severe implications for the interpretation of observational diagnostics, as derived mass-loss rates can be overestimated by factors of 2 to 10 if clumping is ignored, and we describe ongoing attempts to allow for more uniform results. We point out that independent arguments from stellar evolution favor a moderate reduction of present- day mass-loss rates. We also consider larger scale wind structure, interpreted in terms of co-rotating interacting regions, and complete this review with a discussion of recent progress on the X-ray line emission from massive stars, highlighting as to how far the analysis of such X-ray line emission can give further clues regarding an adequate description of wind clumping. (Abridged abstract)Comment: Astronomy and Astrophysics Review (accepted

Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam

BACKGROUND: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis

Production of dust by massive stars at high redshift

The large amounts of dust detected in sub-millimeter galaxies and quasars at high redshift pose a challenge to galaxy formation models and theories of cosmic dust formation. At z > 6 only stars of relatively high mass (> 3 Msun) are sufficiently short-lived to be potential stellar sources of dust. This review is devoted to identifying and quantifying the most important stellar channels of rapid dust formation. We ascertain the dust production efficiency of stars in the mass range 3-40 Msun using both observed and theoretical dust yields of evolved massive stars and supernovae (SNe) and provide analytical expressions for the dust production efficiencies in various scenarios. We also address the strong sensitivity of the total dust productivity to the initial mass function. From simple considerations, we find that, in the early Universe, high-mass (> 3 Msun) asymptotic giant branch stars can only be dominant dust producers if SNe generate <~ 3 x 10^-3 Msun of dust whereas SNe prevail if they are more efficient. We address the challenges in inferring dust masses and star-formation rates from observations of high-redshift galaxies. We conclude that significant SN dust production at high redshift is likely required to reproduce current dust mass estimates, possibly coupled with rapid dust grain growth in the interstellar medium.Comment: 72 pages, 9 figures, 5 tables; to be published in The Astronomy and Astrophysics Revie