Association of colorectal cancer with pathogenic Escherichia coli: Focus on mechanisms using optical imaging

AIM: To investigate the molecular or cellular mechanisms related to the infection of epithelial colonic mucosa by pks-positive Escherichia coli (E. coli) using optical imaging. METHODS: We choose to evaluate the tumor metabolic activity using a fluorodeoxyglucose analogue as 2-deoxyglucosone fluorescent probes and to correlate it with tumoral volume (mm³). Inflammation measuring myeloperoxidase (MPO) activity and reactive oxygen species production was monitored by a bioluminescent (BLI) inflammation probe and related to histological examination and MPO levels by enzyme-linked immunosorbent assay (ELISA) on tumor specimens. The detection and quantitation of these two signals were validated on a xenograft model of human colon adenocarcinoma epithelial cells (HCT116) in nude mice infected with a pks-positive E. coli. The inflammatory BLI signal was validated intra-digestively in the colitis-CEABAC10 DSS models, which mimicked Crohn’s disease. RESULTS: Using a 2-deoxyglucosone fluorescent probe, we observed a high and specific HCT116 tumor uptake in correlation with tumoral volume (P = 0.0036). Using the inflammation probe targeting MPO, we detected a rapid systemic elimination and a significant increase of the BLI signal in the pks-positive E. coli-infected HCT116 xenograft group (P < 0.005). ELISA confirmed that MPO levels were significantly higher (1556 ± 313.6 vs 234.6 ± 121.6 ng/mL P = 0.001) in xenografts infected with the pathogenic E. coli strain. Moreover, histological examination of tumor samples confirmed massive infiltration of pks-positive E. coli-infected HCT116 tumors by inflammatory cells compared to the uninfected group. These data showed that infection with the pathogenic E. coli strain enhanced inflammation and ROS production in tumors before tumor growth. Moreover, we demonstrated that the intra-digestive monitoring of inflammation is feasible in a reference colitis murine model (CEABAC10/DSS). CONCLUSION: Using BLI and fluorescence optical imaging, we provided tools to better understand host-pathogen interactions at the early stage of disease, such as inflammatory bowel disease and colorectal cancer.     

Locoregional treatment of early breast cancer with isolated tumor cells or micrometastases on sentinel lymph node biopsy

The advent of sentinel lymph-node technique has led to a shift in lymph-node staging, due to the emergence of new entities namely micrometastases (pN1mi) and isolated tumor cells [pN0(i+)]. The prognostic significance of this low positivity in axillary lymph nodes is currently debated, as is, therefore its management. This article provides updates evidence-based medicine data to take into account for treatment decision-making in this setting, discussing the locoregional treatment in pN0(i+) and pN1mi patients (completion axillary dissection, axillary irradiation with or without regional nodes irradiation, or observation), according to systemic treatment, with the goal to help physicians in their daily practice.     

Low back pain-related meta-analysis: Caution is needed when interpreting published research results

The systematic reviews (SRs) including a meta-analysis are considered as the top level of evidence. Although the existence of more than a hundred of low back pain (LBP)-related SRs seems very appealing and might therefore suggest significant evidence on the topic, a deep analysis indicates that several of these SRs included only very few studies. Other SRs raise concerns because they included some randomized controlled trials which had a low methodological quality, or some studies which differed significantly regarding the studied populations and/or the experimental procedure. The sometimes controversial results of different SRs conducted on the same topic also highlight the significant influence of the inclusion/exclusion criteria used in the SRs to select the articles. To conclude, although meta-analysis is at the top of the evidence pyramid and have several strengths, the conclusions drawn from SRs should always be interpreted with caution because they can also have weaknesses. This is true, whether it be for LBP-related SRs including a meta-analysis, or any other. Therefore a critical analysis of any SR is always needed before integrating the results of the SR in its own clinical practice. Furthermore, clinical reasoning remains crucial, especially to consider the potential differences between one’s patient and the patients included in the meta-analysis.     

Non-pharmacological intervention for posterior cortical atrophy

Posterior cortical atrophy (PCA) is a rare neurodegenerative condition characterized by progressive visual-perceptual deficits. Although the neurocognitive profile of PCA is a growing and relatively well-established field, non-pharmacological care remains understudied and to be widely established in clinical practice. In the present work we review the available literature on non-pharmacological approaches for PCA, such as cognitive rehabilitation including individual cognitive exercises and compensatory techniques to improve autonomy in daily life, and psycho-education aiming to inform people with PCA about the nature of their visual deficits and limits of cognitive rehabilitation. The reviewed studies represented a total of 7 patients. There is a scarcity of the number of studies, and mostly consisting of case studies. Results suggest non-pharmacological intervention to be a potentially beneficial approach for the partial compensation of deficits, improvement of daily functionality and improvement of quality of life. Clinical implications and future directions are also highlighted for the advancement of the field, in order to clarify the possible role of non-pharmacological interventions, and its extent, in PCA.     

Screening and diagnosis of endometrial cancer in Lynch syndrome

Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition syndrome caused by a mismatch of DNA repair (MMR system). Lifetime risk of developing endometrial and ovarian cancer in LS is higher than in the general population and gynecologic screening appears interesting. Screening is based on several tests: pelvic ultrasound, endometrial biopsy and hysteroscopy for endometrial cancer, pelvic ultrasound and CA125 for ovarian cancer. Those tests appear efficient for the diagnosis of gynecologic cancers in LS. Nevertheless, screening tests have not proved clinical benefit until now, and potential problems of compliance, risk of false negative cases, and interval cancer associated with screening do justify offering prophylactic surgery to patients. Women with LS should be informed of the potential benefits and risks of screening and the importance of evaluation in case of gynecologic symptoms or abnormal bleeding. Chemoprevention by progestin-containing oral contraceptives and the treatment of premalignant lesion are available options for reducing the risk of endometrial cancer in LS population.     

A New Family of High Order Unstructured MOOD and ADER Finite Volume Schemes for Multidimensional Systems of Hyperbolic Conservation Laws

In this paper, we investigate the coupling of the Multi-dimensional Optimal Order Detection (MOOD) method and the Arbitrary high order DERivatives (ADER) approach in order to design a new high order accurate, robust and computationally efficient Finite Volume (FV) scheme dedicated to solving nonlinear systems of hyperbolic conservation laws on unstructured triangular and tetrahedral meshes in two and three space dimensions, respectively. The Multi-dimensional Optimal Order Detection (MOOD) method for 2D and 3D geometries has been introduced in a recent series of papers for mixed unstructured meshes. It is an arbitrary high-order accurate Finite Volume scheme in space, using polynomial reconstructions with a posteriori detection and polynomial degree decrementing processes to deal with shock waves and other discontinuities. In the following work, the time discretization is performed with an elegant and efficient one-step ADER procedure. Doing so, we retain the good properties of the MOOD scheme, that is to say, the optimal high-order of accuracy is reached on smooth solutions, while spurious oscillations near singularities are prevented. The ADER technique not only reduces the cost of the overall scheme as shown on a set of numerical tests in 2D and 3D, but also increases the stability of the overall scheme. A systematic comparison between classical unstructured ADER-WENO schemes and the new ADER-MOOD approach has been carried out for high-order schemes in space and time in terms of cost, robustness, accuracy and efficiency. The main finding of this paper is that the combination of ADER with MOOD generally outperforms the one of ADER and WENO either because at given accuracy MOOD isless expensive (memory and/or CPU time), or because it is more accurate for a given grid resolution. A large suite of classical numerical test problems has been solved on unstructured meshes for three challenging multi-dimensional systems of conservation laws: the Euler equations of compressible gas dynamics, the classical equations of ideal magneto-Hydrodynamics (MHD) and finally the relativistic MHD equations (RMHD), which constitutes a particularly challenging nonlinear system of hyperbolic partial differential equation. All tests are run on genuinely unstructured grids composed of simplex elements.     

Undernutrition,risk of malnutrition and obesity in gastroenterological patients: A multicenter study

AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last three-six months. Values of Malnutrition Universal Screening Tool (MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.     

Is breast conservative surgery a reasonable option in multifocal or multicentric tumors?

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A meta-analysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists.     

Arterial blood gases during exercise: Validity of transcutaneous measurements

OBJECTIVE: To investigate the validity of transcutaneous measurements of blood gas tensions for the assessment of partial arterial pressure of oxygen (PaO(2)) and carbon dioxide (PaCO(2)) during treadmill exercise. DESIGN: Experimental, self-controlled against a reference standard. SETTING: Lung function laboratory. PATIENTS: Eighty-one patients with various lung diseases. INTERVENTIONS: At rest and at symptom-limited peak exercise, puncture of the radial artery with concurrent transcutaneous measures of blood gases. MAIN OUTCOME MEASURES: Arterial blood samples were analyzed with a radiometer to measure PaO(2) and PaCO(2). A microgas apparatus was used to measure gas tensions transcutaneously. Values obtained transcutaneously (TcPO(2), TcPCO(2)) were compared with those obtained by blood sample. TcPO(2) was adjusted as close as possible to the PaO(2) obtained in the same conditions, with the correction factor of the apparatus. Values obtained transcutaneously were compared with those obtained by blood sample to establish the sensitivity and specificity of the noninvasive method. RESULTS: Mean differences +/- standard deviation between transcutaneous and arterial tension at peak exercise were 0.4 +/- 7.0mmHg and 2.1 +/- 3.3mmHg for PaO(2) and PaCO(2), respectively. The transcutaneous device enabled us to predict a decrease in PaO(2) (>or=2mmHg) from rest to exercise with a sensitivity of 92.1% and a specificity of 90% and an increase in PaCO(2) with a sensitivity of 88% and a specificity of 58.9%. CONCLUSIONS: Although transcutaneous measurement are sufficiently sensitive and specific to detect patients whose PaO(2) decreases during exercise, its precision is not sufficient for gas exchange calculations.