Advances in imaging of the solitary pulmonary nodule

Objective. To review the radiological management of a solitary pulmonary nodule. Data sources. MEDLINE literature search (1958-2002). Study selection. All review articles and original articles. Key words for the literature search were 'solitary pulmonary nodule' and 'imaging'. Data extraction. All relevant information and data. Data synthesis. The solitary pulmonary nodule remains a perennial problem in radiological practice, particularly with current trends using low-dose computed tomography to screen for lung cancer. Determining the likelihood of malignancy forms the basis of the radiological approach of a solitary pulmonary nodule. Several factors that influence risk analysis include morphological and enhancement characteristics of the solitary pulmonary nodule on imaging, stability of the nodule, age of patient, smoking history, and history of malignant disease. Other ancillary procedures and imaging techniques that assist in the evaluation of a solitary pulmonary nodule include fluorodeoxyglucose positron-emission tomography, technetium Tc 99m depreotide imaging, bronchoscopy with bronchioloalveolar lavage and biopsy, image-guided transthoracic needle aspiration biopsy, video-assisted thorascopic surgery, and thoracotomy. Conclusions. The success of any radiological management of a solitary pulmonary nodule rests on careful clinical evaluation and risk stratification for malignancy before the implementation of appropriate imaging techniques.published_or_final_versio

Report of 2 fatal cases of adult necrotizing fasciitis and toxic shock syndrome caused by Streptococcus agalactiae.

We describe 2 cases of fatal necrotizing fasciitis and toxic shock syndrome caused by Streptococcus agalactiae-a rare entity that has been reported in only 9 patients-in 2 nonpregnant adults.published_or_final_versio

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

Background:The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).Methods:We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.Results: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P0.03), to occur in pre-menopausal women (P0.002), and to be either ER-positive (P0.002) or HER2-positive (P0.0005), but less likely to be treated with breast-conserving surgery (P0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P0.02), and declined as the DCIS enlarged (P0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).Conclusion:IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens. © 2010 Cancer Research UK All rights reserved.published_or_final_versio

A computed tomography based study on rotational alignment accuracy of the femoral component in total knee arthroplasty using computer-assisted orthopaedic surgery

Rotation of the femoral component in total knee arthroplasty (TKA) is of high importance in respect of the balancing of the knee and the patellofemoral joint. Though it is shown that computer assisted surgery (CAOS) improves the anteroposterior (AP) alignment in TKA, it is still unknown whether navigation helps in finding the accurate rotation or even improving rotation. Therefore the aim of our study was to evaluate the postoperative femoral component rotation on computed tomography (CT) with the intraoperative data of the navigation system. In 20 navigated TKAs the difference between the intraoperative stored rotation data of the femoral component and the postoperative rotation on CT was measured using the condylar twist angle (CTA). This is the angle between the epicondylar axis and the posterior condylar axis. Statistical analysis consisted of the intraclass correlation coefficient (ICC) and Bland-Altman plot. The mean intraoperative rotation CTA based on CAOS was 3.5° (range 2.4–8.6°). The postoperative CT scan showed a mean CTA of 4.0° (1.7–7.2). The ICC between the two observers was 0.81, and within observers this was 0.84 and 0.82, respectively. However, the ICC of the CAOS CTA versus the postoperative CT CTA was only 0.38. Though CAOS is being used for optimising the position of a TKA, this study shows that the (virtual) individual rotational position of the femoral component using a CAOS system is significantly different from the position on a postoperative CT scan

Determining Peptide Partitioning Properties via Computer Simulation

The transfer of polypeptide segments into lipid bilayers to form transmembrane helices represents the crucial first step in cellular membrane protein folding and assembly. This process is driven by complex and poorly understood atomic interactions of peptides with the lipid bilayer environment. The lack of suitable experimental techniques that can resolve these processes both at atomic resolution and nanosecond timescales has spurred the development of computational techniques. In this review, we summarize the significant progress achieved in the last few years in elucidating the partitioning of peptides into lipid bilayer membranes using atomic detail molecular dynamics simulations. Indeed, partitioning simulations can now provide a wealth of structural and dynamic information. Furthermore, we show that peptide-induced bilayer distortions, insertion pathways, transfer free energies, and kinetic insertion barriers are now accurate enough to complement experiments. Further advances in simulation methods and force field parameter accuracy promise to turn molecular dynamics simulations into a powerful tool for investigating a wide range of membrane active peptide phenomena

Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. © 2009 Springer-Verlag.postprin

Rise and Fall of an Anti-MUC1 Specific Antibody

So far, human antibodies with good affinity and specificity for MUC1, a transmembrane protein overexpressed on breast cancers and ovarian carcinomas, and thus a promising target for therapy, were very difficult to generate.A human scFv antibody was isolated from an immune library derived from breast cancer patients immunised with MUC1. The anti-MUC1 scFv reacted with tumour cells in more than 80% of 228 tissue sections of mamma carcinoma samples, while showing very low reactivity with a large panel of non-tumour tissues. By mutagenesis and phage display, affinity of scFvs was increased up to 500fold to 5,7×10(-10) M. Half-life in serum was improved from below 1 day to more than 4 weeks and was correlated with the dimerisation tendency of the individual scFvs. The scFv bound to T47D and MCF-7 mammalian cancer cell lines were recloned into the scFv-Fc and IgG format resulting in decrease of affinity of one binder. The IgG variants with the highest affinity were tested in mouse xenograft models using MCF-7 and OVCAR tumour cells. However, the experiments showed no significant decrease in tumour growth or increase in the survival rates. To study the reasons for the failure of the xenograft experiments, ADCC was analysed in vitro using MCF-7 and OVCAR3 target cells, revealing a low ADCC, possibly due to internalisation, as detected for MCF-7 cells.Antibody phage display starting with immune libraries and followed by affinity maturation is a powerful strategy to generate high affinity human antibodies to difficult targets, in this case shown by the creation of a highly specific antibody with subnanomolar affinity to a very small epitope consisting of four amino acids. Despite these "best in class" binding parameters, the therapeutic success of this antibody was prevented by the target biology

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe