Screening for colorectal cancer: possible improvements by risk assessment evaluation?

Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities are available, an international consensus on screening procedures is still not established. The rather limited compliance in present screening procedures is a significant drawback. Furthermore, some of the procedures are costly and, therefore, selection methods for these procedures are needed. Current research into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among the screening populations, and thereby improve the compliances. Furthermore, the involvement of the media, including social media, may add even more individuals to the screening programs. Implementation of validated RAE and progressively improved screening methods may reform the cost/benefit of screening procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest.     

Hypertension and renovascular disease: follow-up on 100 renal vein renin samplings

The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21%), nephrectomy (20%), or vascular surgery (8%). Seven patients (15%) were cured and 15 (32%) had improved (reduction in antihypertensive medicine) after 6 months follow-up, whereas three patients (6%) were cured and 12 (26%) improved after 3-4 years follow-up. Thus, the number of patients cured or improved is comparable with the results from our department reported 20 years ago. However, in the present report, more than twice as many patients were enrolled, leading to double costs. Different indices of lateralisation of the renin generation were calculated for the use in cases of a shrunken kidney (functional share < or =15%). None of the indices clearly discriminated between the patients who did benefit from intervention, and those who did not. The only positive finding was that a peripheral renin concentration lower than 8 mlU/l predicted no effect of intervention, which might lead to the exclusion of 11% of the patients before entering the diagnostic programme. We conclude that the RVRS demands a very restrictive referral pattern if it should be of prognostic value for the blood pressure outcome after intervention. No indices of lateralised renin concentrations proved high predictive value. However, a peripheral renin concentration low in the normal range seems useful as an indicator of no benefit from intervention.     

Phenotypic detection of constitutive and inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus on routine susceptibility plate

Increasing frequency of methicillin resistant Staphylococcus aureus infections and changing patterns in antimicrobial resistance have led to renewed interest in the use of macrolidelincosamide-streptogramin antibiotics. However therapy may fail either due to constitutive or inducible resistance. This study was undertaken to detect different phenotypes including inducible clindamycin resistance in clinical isolates of Staphylococcus aureus and coagulase negative Staphylococcus. Four hundred sixty five Staphylococcus aureus and 84 coagulase negative Staphylococci isolated from different clinical specimens were included in the study. On routine susceptibility testing plate clindamycin (2 microg) disk was placed at a distance of 15mm towards the centre from a peripherally placed erythromycin (15 microg) disk. Fisher exact test was used for statistical analysis. Out of 465 Staphylococcus aureus isolates, 237 (50.96%) were methicillin sensitive (MSSA) and 228 (49.03%) methicillin resistant (MLS(B)c).Over all 118 (25.37%) isolates showed constitutive resistance (MLS(B)c), 70 (15.05%) inducible clindamycin resistance, 143 (30.75%) MS(B) phenotype and 134 (28.81%) were susceptible to both erythromycin as well as clindamycin. Constitutive and inducible resistance to clindamycin were significantly higher in MRSA than MSSA (P=0.0000 and 0.0001 respectively). Out of 84 isolates of coagulase negative Staphylococci, 43 (51.19%) were methicillin sensitive (MSCNS) and 41(48.80%) methicillin resistant (MRCNS). Constitutive MLS(B) resistance was detected in 32 (38.09%), inducible clindamycin resistance 10 (11.90%), MS(B) phenotype 27 (32.14%) and 15 (17.85%) were susceptible to both erythromycin and clindamycin. Performing D test on a routine susceptibility plate saves material, manpower and time as inducible resistance can be reported simultaneously along with other susceptibility results.     

Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis

The therapeutic efficacy of a slightly acidic, buffered suspension of 1000 mg 5-aminosalicylic acid (Pentasa^®) was compared with that of 25 mg prednisolone following daily rectal administration to outpatients with mild to moderate proctosigmoiditis. The study was carried out as a randomized, double-blind trial in seven gastroenterological departments. A total of 123 patients were included of whom 114 completed the study (53 5-aminosalicylic acid, 61 prednisolone). The patient population was representative for the disease as it ordinarily appears in medical outpatient clinics. After 14 days, patients in total remission discontinued the treatment, while the rest were treated for another two-week period. Improvement or remission was seen in 77% of the 5-aminosalicylic acid-treated patients and in 72% of the prednisolone-treated patients (P>0.05). More than half the patients requiring prolonged treatment benefited from it, which points to an advantage of extended therapy. Side effects were few and mild. It is concluded that the applied suspension of 5-aminosalicylic acid is at least as efficient as prednisolone for topical treatment of patients with slightly to moderately active proctosigmoiditis.The group includes: Vibeke Binder, MD, Stig Bondesen, MD, Olaf Bonnevie, MD, Knud Christian Christensen MD, Lisbeth Ambrosius Christensen, MD, Poul Danø, MD, Hans Draminsky Petersen, MD, Troels Havelund, MD, Eigill F. Hvidberg, MD, Oli Jacobsen, MD, Karin Ladefoged, MD, Karsten Lauritsen, MD, Laurits Stærk Laursen, MD, Jørgen Rask-Madsen, MD, Sten Nørby Rasmussen, MD, German Sanchez, MD, Poul Schlichting, MD, Ulrik Tage-Jensen, MD, Mogens Vilien, MD, Johann Wandall, MD.     

Influence of Bentonite on Mechanical and Durability Properties of High-Calcium Fly Ash Geopolymer Concrete with Natural and Recycled Aggregates

In this study, bentonite (a naturally occurring pozzolana) was incorporated as a partial replacement (up to 20%) for high-calcium fly ash (HCFA)-based geopolymeric natural aggregate concrete (GNAC) and geopolymeric recycled aggregate concrete (GRAC). The mechanical (compressive strength and splitting tensile strength), durability (chloride migration coefficient, water absorption, and acid attack resistance), and rheological properties (slump test, fresh density, and workability) were investigated. The results revealed that incorporation of bentonite (10 wt % with ordinary Portland cement) showed appreciable improvement in the strength and durability of both the GNAC and GRAC, though its effect is more significant for GRAC than the GNAC.     

Survival after elective surgery for colonic cancer in Denmark

Aim Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. Method Data from the National Colorectal Cancer Database were analysed. This includes about 95% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001–2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001–2004 and 2005–2008. Results 9149 patients were included for the final analysis. The overall 5‐year survival rates were 0.65 in 2001–2004 and 0.66 in 2005–2008. The relative 5‐year survival rates were also within 1% of each other. None of these comparisons was statistically significant. Conclusion Survival following elective colon cancer surgery has been almost unchanged since 2001.     

Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis

Efferocytosis, the process through which apoptotic cells (ACs) are cleared through actin-mediated engulfment by macrophages, prevents secondary necrosis, suppresses inflammation, and promotes resolution. Impaired efferocytosis drives the formation of clinically dangerous necrotic atherosclerotic plaques, the underlying etiology of coronary artery disease (CAD). An intron of the gene encoding PHACTR1 contains rs9349379 (A>G), a common variant associated with CAD. As PHACTR1 is an actin-binding protein, we reasoned that if the rs9349379 risk allele G causes lower PHACTR1 expression in macrophages, it might link the risk allele to CAD via impaired efferocytosis. We show here that rs9349379-G/G was associated with lower levels of PHACTR1 and impaired efferocytosis in human monocyte–derived macrophages and human atherosclerotic lesional macrophages compared with rs9349379-A/A. Silencing PHACTR1 in human and mouse macrophages compromised AC engulfment, and Western diet–fed Ldlr^–/– mice in which hematopoietic Phactr1 was genetically targeted showed impaired lesional efferocytosis, increased plaque necrosis, and thinner fibrous caps — all signs of vulnerable plaques in humans. Mechanistically, PHACTR1 prevented dephosphorylation of myosin light chain (MLC), which was necessary for AC engulfment. In summary, rs9349379-G lowered PHACTR1, which, by lowering phospho-MLC, compromised efferocytosis. Thus, rs9349379-G may contribute to CAD risk, at least in part, by impairing atherosclerotic lesional macrophage efferocytosis.     

Theoretical model for laser ablation outcome predictions in brain: calibration and validation on clinical MR thermometry images

Purpose: Neurosurgical laser ablation is experiencing a renaissance. Computational tools for ablation planning aim to further improve the intervention. Here, global optimisation and inverse problems are demonstrated to train a model that predicts maximum laser ablation extent.

Methods: A closed-form steady state model is trained on and then subsequently compared to N?=?20 retrospective clinical MR thermometry datasets. Dice similarity coefficient (DSC) is calculated to provide a measure of region overlap between the 57?°C isotherms of the thermometry data and the model-predicted ablation regions; 57?°C is a tissue death surrogate at thermal steady state. A global optimisation scheme samples the dominant model parameter sensitivities, blood perfusion (ω) and optical parameter (μ_eff) values, throughout a parameter space totalling 11?440 value-pairs. This represents a lookup table of μ_eff–ω pairs with the corresponding DSC value for each patient dataset. The μ_eff–ω pair with the maximum DSC calibrates the model parameters, maximising predictive value for each patient. Finally, leave-one-out cross-validation with global optimisation information trains the model on the entire clinical dataset, and compares against the model naïvely using literature values for ω and μ_eff.

Results: When using naïve literature values, the model’s mean DSC is 0.67 whereas the calibrated model produces 0.82 during cross-validation, an improvement of 0.15 in overlap with the patient data. The 95% confidence interval of the mean difference is 0.083–0.23 (p?Conclusions: During cross-validation, the calibrated model is superior to the naïve model as measured by DSC, with +22% mean prediction accuracy. Calibration empowers a relatively simple model to become more predictive.