CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

Purpose

Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population.

Methods

In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas.

Results

In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma ≥10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88–96) vs. 96% (95% CI: 93–99) for colonoscopy (P = 0.26). For adenomas and carcinomas ≥10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89–97) vs. 97% (95% CI: 94–99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas ≥10 mm was 95% (95% CI: 91–99) for CTC vs. 99% (95% CI: 98–100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86–95) and 96% (95% CI: 94–99), respectively (P < 0.001).

Conclusion

CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.     

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: Bivariate meta-analysis and decision analysis

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia.An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed with a bivariate model estimating a summary Receiver Operating Characteristic (sROC) curve. Subsequently, a clinical decision analysis was performed, in which three alternative strategies were modelled: (I) expectant management with monitoring until spontaneous labour; (II) induction of labour; (III) serum uric acid as test for predicting maternal complications. In the latter strategy, accuracy data of serum uric acid derived from the sROC curve were used to assess the value of serum uric acid in the management of women with pre-eclampsia. In this strategy, women with an increased serum uric acid were supposed to have labour induced, whereas women with serum uric acid levels below the threshold were managed expectantly. The decision whether to use the policy expectant management, to induce labour or to test serum uric acid levels, is based on the expected utility of each strategy. The expected utility depends on the probability of occurrence of severe maternal complications (i.e. severe hypertension, haemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) or eclampsia) and the mode of delivery (caesarean section versus vaginal delivery). Valuation of the outcomes was performed using a distress ratio, which expresses how much worse a complication of pre-eclampsia is valued as compared to a caesarean section.Eight studies, testing 1565 women with pre-eclampsia, met the inclusion criteria. If the distress ratio was 10, the strategy regarding serum uric acid would be the preferred strategy when the probability of complications was between 2.9 and 6.3%. At higher complication rates induction of labour would be preferred, whereas at lower complication rates expectant management would be the best treatment option. These findings were stable in sensitivity analyses, using different distress ratios.Based on the decision analysis, serum uric acid seems to be a useful test in the management of pre-eclampsia under realistic assumptions.     

Vaccination and Antibody Testing in Cats

Vaccines protect cats from serious diseases by inducing antibodies and cellular immune responses. Primary vaccinations and boosters are given according to vaccination guidelines provided by industry and veterinary organizations, based on minimal duration of immunity (DOI). For certain diseases, particularly feline panleukopenia, antibody titres correlate with protection. For feline calicivirus and feline herpesvirus, a similar correlation is absent, or less clear. In this review, the European Advisory Board on Cat Diseases (ABCD) presents current knowledge and expert opinion on the use of antibody testing in different situations. Antibody testing can be performed either in diagnostic laboratories, or in veterinary practice using point of care (POC) tests, and can be applied for several purposes, such as to provide evidence that a successful immune response was induced following vaccination. In adult cats, antibody test results can inform the appropriate re-vaccination interval. In shelters, antibody testing can support the control of FPV outbreaks by identifying potentially unprotected cats. Antibody testing has also been proposed to support decisions on optimal vaccination schedules for the individual kitten. However, such testing is still expensive and it is considered impractical to monitor the decline of maternally derived antibodies.     

Vasorelaxant effects and mechanisms of action of Heracleum sphondylium L. (Apiaceae) in rat thoracic aorta

Ethnopharmacological relevance

Aerial parts of Heracleum sphondylium L. (HS) are used in traditional medicine to treat hypertension. To provide pharmacological basis for this use, we investigated the vasorelaxant effects of a dichloromethane extract of HS (HSDE) and the mechanisms involved.

Materials and methods

Activity of HSDE was evaluated on rat isolated thoracic aortic rings.

Results

HSDE induced vasorelaxation in phenylephrine (PE, 10⁻⁶ mol/L) and high KCl—(6×10⁻² mol/L) pre-contracted aortic rings that was independent on the presence of endothelium. HSDE markedly decreased extracellular Ca²⁺-induced contraction in high-KCl and PE pre-challenged rings. It also inhibited the intracellular Ca²⁺ release sensitive to PE (10⁻⁶ M). The relaxant effect of HSDE were blunted by 4-amino-pyridine (4-AP, 10⁻³ mol/L), an inhibitor of voltage-dependent K⁺ channels.

Conclusion

Our results provide the first evidence that a dichloromethane extract of Heracleum sphondylium L. exhibits vasorelaxant properties through endothelium-independent mechanisms involving the inhibition of Ca²⁺ mobilization and changes in Kv channel conductances. These data argue for its use as antihypertensive therapy in traditional medicine.     

Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person

We detected a highly divergent SARS-CoV-2 Alpha variant in an immunocompromised person several months after the latest detection of the Alpha variant in the Netherlands. The patient was infected for 42 weeks despite several treatment regimens and disappearance of most clinical symptoms. We identified several potential immune escape mutations in the spike protein.     

Rabies Virus Populations in Humans and Mice Show Minor Inter-Host Variability within Various Central Nervous System Regions and Peripheral Tissues

Rabies virus (RABV) has a broad host range and infects multiple cell types throughout the infection cycle. Next-generation sequencing (NGS) and minor variant analysis are powerful tools for studying virus populations within specific hosts and tissues, leading to novel insights into the mechanisms of host-switching and key factors for infecting specific cell types. In this study we investigated RABV populations and minor variants in both original (non-passaged) samples and in vitro-passaged isolates of various CNS regions (hippocampus, medulla oblongata and spinal cord) of a fatal human rabies case, and of multiple CNS and non-CNS tissues of experimentally infected mice. No differences in virus populations were detected between the human CNS regions, and only one non-synonymous single nucleotide polymorphism (SNP) was detected in the fifth in vitro passage of virus isolated from the spinal cord. However, the appearance of this SNP shows the importance of sequencing newly passaged virus stocks before further use. Similarly, we did not detect apparent differences in virus populations isolated from different CNS and non-CNS tissues of experimentally infected mice. Sequencing of viruses obtained from pharyngeal swab and salivary gland proved difficult, and we propose methods for improving sampling.     

Effects of the Anticancer Agent Vinorelbine on Endothelial Cell Permeability and Tissue-factor Production in Man

Because antineoplastic drugs could increase endothelial blood barrier permeability and thrombotic diseases have been described as a complication of treatments with vinca alkaloids, the effect of a therapeutic dose (10-⁸ M) of vinorelbine on transendothelial permeability was analysed by measuring the movement of albumin across a monolayer of human venous endothelial cells. Induction of procoagulant activity was assessed by evaluation of tissue-factor activity in cell lysates. Vinorelbine increased the permeability of endothelial cells after 3 h of culture, as observed with thrombin. In addition, thrombin induced strong tissue-factor activity, a phenomenon not observed after vinorelbine treatment. These data suggest that vinorelbine could modulate endothelial barrier permeability. This effect is not linked to an increase in tissue-factor activity, suggesting that their induction could operate through separate pathways.