Lymphocoele: a rare and little known complication of anterior lumbar surgery.

Lymphocoele is a rare and little known complication with only a handful of reports available. We report two cases of lymphocoele after anterior lumbar surgery that have occurred in two different centres and discuss diagnosis and management options. The first case is that of a 53-year-old male patient undergoing two level anterior lumbar interbody fusion (ALIF) for disabling back pain due to disc degeneration in the context of an old spondylodiscitis. He developed a large fluid mass postoperatively. Fluid levels of creatinin were low and intravenous urography ruled out a urinoma suggesting the diagnosis of a lymphocoele. Following two unsuccessful drainage attempts he underwent a laparoscopic marsupialization. The second case was that of a 32-year-old female patient developing a large fluid mass following a L5 corpectomy for a burst fracture. She was treated successfully with insertion of a vacuum drain during 7 days. Lymphocoele is a rare complication but should be suspected if fluid collects postoperatively following anterior lumbar spine procedures. Chemical analysis of the fluid can help in diagnosis. Modern treatment consists of laparoscopic marsupialization. Lymph vessel anatomy should be borne in mind while exposing the anterior lumbar spine.

Incretins: what is known, new and controversial in 2013?

Glucagon-like peptide (GLP)-1 action involves both endocrine and neural pathways to control peripheral tissues. In diabetes the impairment of either pathway may define different subsets of patients: some may be better treated with GLP-1 receptor agonists that are more likely to directly stimulate beta-cells and extrapancreatic receptors, while others may benefit from dipeptidyl peptidase (DPP)-4 inhibitor treatments that are more likely to increase the neural gut-brain-pancreas axis. Elevated plasma concentrations of GLP-1 associated with agonist treatment or bariatric surgery also appear to exert neuroprotective effects, ameliorate postprandial and fasting lipids, improve heart physiology and protect against heart failure, thereby expanding the possible positioning of GLP-1-based therapies. However, the mechanisms behind GLP-1 secretion, the role played by proximal and distal intestinal GLP-1-producing cells as well as the molecular basis of GLP-1 resistance in diabetes are still to be ascertained. The pharmacological features distinguishing GLP-1 receptor agonists from DPP-4 inhibitors are discussed here to address their respective positions in type 2 diabetes.

False identity documents forensic profiling: study of known-sources and cross-border seizures

A forensic intelligence process was conducted over cross-border seizures of false identity documents whose sources were partly known to be the same. Visual features of 300 counterfeit Portuguese and French identity cards seized in France and Switzerland were observed and integrated in a structured database developed to detect and analyze forensic links. Based on a few batches of documents known to come from common sources, the forensic profiling method could be validated and its performance evaluated. The method also proved efficient and complementary to conventional means of detecting connections between cases. Cross-border links were detected, highlighting the need for more collaboration. Forensic intelligence could be produced, uncovering the structure of counterfeits' illegal trade, the concentration of their sources and the evolution of their quality over time. In addition, two case examples illustrated how forensic profiling may support specific investigations. The forensic intelligence process and its results will underline the need to develop such approaches to support the fight against fraudulent documents and organized crime.

Incremental Prognostic Value of Myocardial Blood Flow Quantification with Rb-82 Cardiac PET in Patients With Known or Suspected CAD

Rb-82cardiac PET has been used to non-invasively assess myocardial blood flow (MBF)and myocardial flow reserve (MFR). The impact of MBF and MFR for predictingmajor adverse cardiovascular events (MACE) has not been investigated in aprospective study, which was our aim. MATERIAL AND METHODS: In total, 280patients (65±10y, 36% women) with known or suspected CAD were prospectivelyenrolled. They all underwent both a rest and adenosine stress Rb-82 cardiacPET/CT. Dynamic acquisitions were processed with the FlowQuant 2.1.3 softwareand analyzed semi-quantitatively (SSS, SDS) and quantitatively (MBF, MFR) andreported using the 17-segment AHA model. Patients were stratified based on SDS,stress MBF and MFR and allocated into tertiles. For each group, annualizedevent rates were computed by dividing the number of annualized MACE (cardiacdeath, myocardial infarction, revascularisation or hospitalisation forcardiac-related event) by the sum of individual follow-up periods in years.Outcome were analysed for each group using Kaplan-Meier event-free survivalcurves and compared using the log-rank test. Multivariate analysis wasperformed in a stepwise fashion using Cox proportional hazards regressionmodels (p<0.05 for model inclusion). RESULTS: In a median follow-up of 256days (range 168-440d), 44 MACE were observed. Ischemia (SDS≥2) was observed in95 patients who had higher annualized MACE rate as compared to those without(55% vs. 9.8%, p<0.0001). The group with the lowest MFR tertile (MFR<1.76)had higher MACE rate than the two highest tertiles (51% vs. 9% and 14%,p<0.0001). Similarly, the group with the lowest stress MBF tertile(MBF<1.78mL/min/g) had the highest annualized MACE rate (41% vs. 26% and 6%,p=0.0002). On multivariate analysis, the addition of MFR or stress MBF to SDSsignificantly increased the global χ2 (from 56 to 60, p=0.04; and from56 to 63, p=0.01). The best prognostic power was obtained in a model combiningSDS (p<0.001) and stress MBF (p=0.01). Interestingly, the integration ofstress MBF enhanced risk stratification even in absence of ischemia.CONCLUSIONS: Quantification of MBF or MFR in Rb-82 cardiac PET/CT providesindependent and incremental prognostic information over semi-quantitativeassessment with SDS and is of value for risk stratification.

Effets secondaires meconnus des glucocorticoi'des: prevention et traitement spécifiques requis [Some less well known side effects of glucocorticoids: specific prevention and treatment?]

Steroid treatment is required in many clinical settings and if prolonged can be associated with serious side effects. Certain less well-known side effects may require specific prevention, diagnosis and treatment. The risk of developing hyperglycemia, psychiatric disorders and opportunistic infections associated with immunosuppression is often forgotten. We present herein some evidence on the prevalence, preventive measures and treatment of some of these side effects. Large controlled trials are lacking and do not allow to provide strong recommendations. Nevertheless, we try to provide some suggestions based on a review of the literature.

Cardiomyopathie de tako-tsubo: une entité clinique rare et méconnue [Tako-tsubo cardiomyopathy: a rare and badly known clinical entity]

Tako-tsubo cardiomyopathy or "transient left ventricular (LV) apical ballooning" clinically presents like acute myocardial infarction without angiographic stenosis on coronary angiogram and a transient (reversible) LV apical ballooning. We discuss here about a 56-year-old woman complains of first constrictive chest pain with ST elevation in leads V2-V6 and minimal enzymatic release. Coronary angiogram demonstrates vessels without stenosis and the left ventriculogram an extensive LV apical wall motion abnormalities. LV dysfunction will only be transient since 24 hours after admission echographic images demonstrate quite complete recovery of LV systolic function. The pain disappears 12 hours after admission and the creatine kinase level normalize after 48 hours.

Appropriateness of colonoscopy in Europe (EPAGE II). Chronic diarrhea and known inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for investigation of chronic diarrhea, management of patients with known inflammatory bowel disease (IBD), and for colorectal cancer (CRC) surveillance in such patients, and to report report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews, and primary studies regarding the evaluation of chronic diarrhea, the management of IBD, and colorectal cancer surveillance in IBD was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: According to the literature, colonoscopic evaluation may be justified for patients aged > 50 years with recent-onset chronic diarrhea or with alarm symptoms. Surveillance colonoscopy for CRC should be offered to all patients with extensive ulcerative colitis or colonic Crohn's disease of 8 years' duration, and to all patients with less extensive disease of 15 years' duration. Intervals for surveillance colonoscopy depend on duration of evolution, initial diagnosis, and histological findings. The EPAGE II criteria also confirmed the appropriateness of diagnostic colonoscopy for diarrhea of > 4 weeks' duration. They also suggest that, in addition to assessing extent of IBD by colonoscopy, further colonoscopic examination is appropriate in the face of persistent or worsening symptoms. Surveillance colonoscopy in IBD patients was generally appropriate after a lapse of 2 years. In the presence of dysplasia at previous colonoscopy, it was not only appropriate but necessary. CONCLUSIONS: Despite or perhaps because of the limitations of the available published studies, the panel-based EPAGE II (http://www.epage.ch) criteria can help guide appropriate colonoscopy use in the absence of strong evidence from the literature.

Covalent binding of C3b to monoclonal antibodies selectively up-regulates heavy chain epitope recognition by T cells.

Protein C3 of the complement system is known for its role in the nonspecific immune response. Covalent binding of C3b to antigen upon complement activation also plays a significant role in specific T cell immune response. C3b-antigen complexes can bind to complement receptors on the antigen-presenting cell, and the C3b antigen link (most often an ester link) remains fairly stable inside the cells. In this study, IgG1,kappa and IgG2a,kappa murine monoclonal antibodies (mAb) were used as antigens; covalent complexes between mAb and C3b were produced and purified in vitro from purified proteins; human B cell lines and T cell clones were raised from tumor patients who received mAb injections for cancer therapy or diagnosis. Recognition of epitopes of these mAb by T cell clones when the mAb were processed alone or bound to C3b was compared. IgG or IgG-C3b complexes presented by B cell lines were able to stimulate proliferation of kappa light chain-specific T cell clones at similar concentrations. In contrast, IgG-C3b complex recognition by heavy chain-specific T cell clones required 100-fold less IgG-C3b than uncomplexed IgG. As C3b was shown to be covalently bound only to the IgG heavy chains in the complexes, C3b chaperoning is restricted to only the IgG heavy chain and selectively influences intracellular steps of IgG heavy chain processing. This differential modulation of C3b suggests an early dissociation of IgG heavy and light chains in antigen-presenting cells.

Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes.

Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.

The systematic profiling of false identity documents: method validation and performance evaluation using seizures known to originate from common and different sources

False identity documents constitute a potential powerful source of forensic intelligence because they are essential elements of transnational crime and provide cover for organized crime. In previous work, a systematic profiling method using false documents' visual features has been built within a forensic intelligence model. In the current study, the comparison process and metrics lying at the heart of this profiling method are described and evaluated. This evaluation takes advantage of 347 false identity documents of four different types seized in two countries whose sources were known to be common or different (following police investigations and dismantling of counterfeit factories). Intra-source and inter-sources variations were evaluated through the computation of more than 7500 similarity scores. The profiling method could thus be validated and its performance assessed using two complementary approaches to measuring type I and type II error rates: a binary classification and the computation of likelihood ratios. Very low error rates were measured across the four document types, demonstrating the validity and robustness of the method to link documents to a common source or to differentiate them. These results pave the way for an operational implementation of a systematic profiling process integrated in a developed forensic intelligence model.

Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity.

Human inhibitor NF-κB kinase 2 (hIKK-2) is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Thus, synthetic ATP-competitive inhibitors for hIKK-2 have been developed as anti-inflammatory compounds. We recently reported a virtual screening protocol (doi:10.1371/journal.pone.0016903) that is able to identify hIKK-2 inhibitors that are not structurally related to any known molecule that inhibits hIKK-2 and that have never been reported to have anti-inflammatory activity. In this study, a stricter version of this protocol was applied to an in-house database of 29,779 natural products annotated with their natural source. The search identified 274 molecules (isolated from 453 different natural extracts) predicted to inhibit hIKK-2. An exhaustive bibliographic search revealed that anti-inflammatory activity has been previously described for: (a) 36 out of these 453 extracts; and (b) 17 out of 30 virtual screening hits present in these 36 extracts. Only one of the remaining 13 hit molecules in these extracts shows chemical similarity with known synthetic hIKK-2 inhibitors. Therefore, it is plausible that a significant portion of the remaining 12 hit molecules are lead-hopping candidates for the development of new hIKK-2 inhibitors.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

Syndrome hypothénarien du marteau: étiologie peu connue de phénomène de Raynaud secondaire [Hypothenar hammer syndrome: little-known etiology of secondary Raynaud's phenomenon]

Hypothenar hammer syndrome is an uncommonly encountered cause of Raynaud's phenomenon associated with professional or recreational activities. We report 6 consecutive cases seen in our angiology unit between 1988 and 1990. Clinical findings include a history of repeated microtraumatisms of the dominant hand, male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon of the last three fingers. Investigations reveal an aneurysm or thrombosis of the distal cubital artery or of the superficial palmar branch, associated with occlusion of digital arteries. Avoidance of the aggravating conditions or resection and/or plasty of the affected vascular segment usually leads to disappearance of the symptoms.