Different accuracies of rapid enzyme-linked immunosorbent, turbidimetric, and agglutination D-dimer assays for thrombosis exclusion: impact on diagnostic work-ups of outpatients with suspected deep vein thrombosis and pulmonary embolism

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1%, with a negative predictive value of more than 99 to 100% during 3-month follow-up. Compression ultrasonography (CUS) and spiral computed tomography (CT) currently are the methods of choice to confirm or rule out deep venous thrombosis (DVT) and pulmonary embolism (PE), respectively. CUS has a negative predictive value (NPV) of 97 to 98%, indicating the need to improve the diagnostic work-up of patients with suspected DVT by clinical score assessment and D-dimer testing. Spiral CT as a stand-alone method detects all clinically relevant PEs and a large number of alternative diagnoses. It rules out PE with a NPV of 98 to 99%. Spiral CT is expensive, emphasizing the need to improve the diagnostic work-up of patients with suspected PE by the use of clinical score assessment and D-dimer testing. Clinical score assessment for DVT and PE has not safely ruled out VTE in multicenter studies and in routine daily practices. Modification of the Wells clinical score assessment for DVT by elimination of the "minus 2 points" for alternative diagnosis will improve the reproducibility of the clinical score assessment. The combination of a first negative CUS and a negative SimpliRed or an enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer of < 1,000 ng/mL safely exclude DVT (NPV > 99%) irrespective of clinical score assessment and without the need to repeat CUS in approximately 60 to 70% of patients. The rapid quantitative and qualitative agglutination D-dimer assays for the exclusion of VTE are not sensitive enough as stand-alone tests and should be used in combination with clinical score assessment. A normal rapid ELISA VIDAS D-dimer test as a stand-alone test safely excludes DVT and PE, with a NPV of 99 to 100%, irrespective of clinical score, without the need of CUS or spiral CT. The combined strategy of a rapid ELISA VIDAS D-dimer followed by objective testing with CUS for DVT and by spiral CT for PE will reduce the need for noninvasive imaging techniques by 40 to 50%.     

bc-GenExMiner: an easy-to-use online platform for gene prognostic analyses in breast cancer

Gene prognostic meta-analyses should benefit from breast tumour genomic data obtained during the last decade. The aim was to develop a user-friendly, web-based application, based on DNA microarrays results, called “breast cancer Gene-Expression Miner” (bc-GenExMiner) to improve gene prognostic analysis performance by using the same bioinformatics process. bc-GenExMiner was developed as a web-based tool including a MySQL relational database. Survival analyses are performed with R statistical software and packages. Molecular subtyping was performed by means of three single sample predictors (SSPs) and three subtype clustering models (SCMs). Twenty-one public data sets have been included. Among the 3,414 recovered breast cancer patients, 1,209 experienced a pejorative event. Molecular subtyping by means of three SSPs and three SCMs was performed for 3,063 patients. Furthermore, three robust lists of stable subtyped patients were built to maximize reliability of molecular assignment. Gene prognostic analyses are done by means of univariate Cox proportional hazards model and may be conducted on cohorts split by nodal (N), oestrogen receptor (ER), or molecular subtype status. To evaluate independent prognostic impact of genes relative to Nottingham Prognostic Index and Adjuvant! Online, adjusted Cox proportional hazards models are performed. bc-GenExMiner allows researchers without specific computation skills to easily and quickly evaluate the in vivo prognostic role of genes in breast cancer by means of Cox proportional hazards model on large pooled cohorts, which may be split according to different prognostic parameters: N, ER, and molecular subtype. Prognostic analyses by molecular subtype may also be performed in three robust molecular subtype classifications.     

Full virulence of Pseudomonas aeruginosa requires OprF

OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known human opportunistic pathogen associated with severe hospital-acquired sepsis and chronic lung infections of cystic fibrosis patients. A multiphenotypic approach, based on the comparative study of a wild-type strain of P. aeruginosa, its isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is required for P. aeruginosa virulence. The absence of OprF results in impaired adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III secretion system (T3SS), and production of the quorum-sensing-dependent virulence factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-l-homoserine lactone and N-butanoyl-l-homoserine lactone was found to be reduced and delayed, respectively. Pseudomonas quinolone signal (PQS) production was decreased, while its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken together, these results show the involvement of OprF in P. aeruginosa virulence, at least partly through modulation of the quorum-sensing network. This is the first study showing a link between OprF, PQS synthesis, T3SS, and virulence factor production, providing novel insights into virulence expression.     

Modified DWI-FLAIR mismatch guided thrombolysis in unknown onset stroke

Journal of Thrombosis and Thrombolysis - DWI-FLAIR mismatch has been recently proven to identify patients with unknown onset stroke (UOS) eligible for thrombolysis. However, this concept may...     

Aortenklappenersatz mit Homografts Eine übersicht

Zusammenfassung Die Implantation (eigentlich Transplantation) frischer oder kryokonservierter menschlicher Herzklappen (Homografts) in Aortenposition gehört seit über 30 Jahren zum herzchirurgischen Repertoire. Homografts sind attraktive Alternativen zu mechanischen oder xenobiologischen Klappen, da eine Antikoagulation vermieden und eine nahezu normale Anatomie hergestellt werden kann. Behandelnde Ärzte sollten über die verfügbaren Implantate, die Operationsmethoden und die zu erwartenden Ergebnisse informiert sein, um Patienten mit Klappenvitien entsprechend beraten zu können und individuelle Komplikationsmöglichkeiten in der Nachsorge früh zu erfassen. Dargelegt wird eine Literaturübersicht zum Thema Homograftklappen. Es erfolgt eine Schilderung des Verfahrens der Graftgewinnung, der Herstellung und der Konservierung. Die Einsatzgebiete von Homografts werden erläutert und die Operationstechniken (subkoronar, Miniroot, Wurzelersatz) sowie die Ross-Operation diskutiert. Erwähnung findet auch der Einsatz von Homograftklappen bei frühkindlichen Herzfehlern. Komplikationen und wichtige Aspekte der Nachsorge werden kommentiert. Homografts eignen sich zum Aorten- und Pulmonalklappenersatz bei speziellen Indikationen (jugendlicher Patient, Kontraindikation zur Antikoagulation, Endokarditis). Angaben zu Langzeitergebnissen schwanken je nach Zentrum, eingesetzter Operationsmethode und Klappentyp. Pulmonale Homografts in Aortenposition sind im Gegensatz zu aortalen Homografts negativ zu beurteilen. Der Stellenwert von Homografts und der Ross-Operation im Vergleich zu ungestützten Xenografts sollte durch weitere möglichst multizentrische Langzeitstudien überprüft werden. Im Bereich der Kinderherzchirurgie haben sich Homografts bewährt, vor allem zur Rekonstruktion der rechtsventrikulären Ausflussbahn. Homograftimplantate in Mitralposition gehören noch nicht zur klinischen Routine und zeigen bislang enttäuschende Resultate. Die wesentliche Limitation im Einsatz von Homografts ist ihre geringe Verfügbarkeit; deshalb können Homografts nur begrenzt für die oben erwähnten speziellen Indikationen zur Verfügung gestellt werden. Abstract The implantation of fresh or cryopreserved human heart valves (homografts) in aortic position is a tool in cardiac surgery since 30 years. Homografts are attractive alternatives to the implantation of mechanical or xenobiological prostheses, because anticoagulation can be avoided and a near normal anatomy can be restored. Physicians should know about the several kinds of grafts and operative techniques to adequately take care of the patients in follow-up. This overview on the literature covers methods of harvesting, preparation and conservation of homografts according to standard protocols of the European Homograft Bank in Brussels. Their use in the therapy of human valvular disease is discussed with special emphasis to operative techniques (subcoronary, root) and the Ross procedure and in pediatric surgery. Complications and aspects of postoperative care are discussed including immunologic phenomena. Homografts are useful tools for aortic valve replacement, especially in juveniles, in the presence of contraindications for anticoagulation and in endocarditis. Whereas aortic homografts have excellent long-term results, pulmonic homografts show a significant rate of malformation. Further studies should be performed to clarify the role of the Ross operation or stentless xenografts compared to homografts in aortic position. In pediatric cardiac surgery homografts are of value especially for the reconstruction of the right ventricular outflow tract. Homografts in mitral position show dissapointing results up to now. The major limitation in the use of homografts is the mismatch of availability and request, therefore homografts can only be used for the above mentioned special indications.     

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)—A multicenter phase-II trial (CISTAXOL)

Background

Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German–French phase-II trial with trimodality.

Patients and methods

Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50 mg/m² day 1 + 8) and paclitaxel (175 mg/m² d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin 50 mg/m² day 2 + 9 and etoposide 100 mg/m² d 4–6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for this cohort.

Results

All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33–69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment – histopathology (squamous/adeno) – age (<50/≥50) – Charlson-CI: 1/>1 – BMI (≥25/<25) – pack years smoking (≥10/<10); treatment-dependent – R0/no-R0.

Conclusions

This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).     

Does dorsal processing require central capacity? More evidence from the PRP paradigm

The human vision system appears to divide into two streams: a ventral stream from V1 to the inferior temporal cortex processing ‘vision for perception’, and a dorsal stream from V1 to the posterior parietal cortex processing ‘vision for action’. Among other characteristics, it has been suggested that dorsal processing is effortless, unconscious, and not bearing on central cognitive resources implicated in ventral processing. The present study shows that a typical dorsal task (i.e., grasping an object) is subject to a classical indicator of capacity limitations in dual-task situations, the psychological refractory period (PRP) effect. In particular, response times to task 2 (the grasping task) increased the more the two tasks overlapped in time, i.e., the shorter the time interval between the stimuli of the two tasks was. As is also common in PRP experiments, response times to task 1 were largely unaffected by this variation. The PRP effect was obtained despite careful control of strategic response deferment, and peripheral overlap of response modalities that may have artificially created performance costs in previous studies. Altogether, the present results show that dorsal processing is subject to the same capacity limitations that can almost universally be found with simple cognitive tasks.     

Good vibrations? Vibrotactile self-stimulation reveals anticipation of body-related action effects in motor control

Previous research suggests that motor actions are intentionally generated by recollecting their sensory consequences. Whereas this has been shown to apply to visual or auditory consequences in the environment, surprisingly little is known about the contribution of immediate, body-related consequences, such as proprioceptive and tactile reafferences. Here, we report evidence for a contribution of vibrotactile reafferences to action selection by using a response–effect compatibility paradigm. More precisely, anticipating actions to cause spatially incompatible vibrations delayed responding to a small but reliable degree. Whereas this observation suggests functional equivalence of body-related and environment-related reafferences to action control, the future application of the described experimental procedure might reveal functional peculiarities of specific types of sensory consequences in action control.