Sulfadoxine-pyrimethamine resistance and intermittent preventive treatment during pregnancy: a retrospective analysis of birth weight data in the Democratic Republic of Congo (DRC)

Objective To assess the effect of intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp‐SP) on birth weight in sites with varying degrees of drug resistance. Methods Birth weight data from three regions in Democratic Republic of Congo with varying degrees of sulfadoxine–pyrimethamine (SP) resistance (1.6% in Mikalayi, 21.7% in Kisangani and 60.6% in Rutshuru) were analysed retrospectively by means of a logistic model that included the number of SP doses taken by the mother and other potentials confounding factors. Results The IPTp‐SP reduced the risk of low birth weight (LBW) in Kisangani (adjusted OR, 0.15; IC95%, 0.05–0.46) and in Mikalayi (adjusted OR, 0.12; IC95%, 0.01–0.89). In both sites, the average birth weight was higher for mothers having received two rather than one or no SP doses (P < 0.001). In Rutshuru, IPTp‐SP had an effect in primigravidae but not in multigravidae. However, after adjustment for other LBW risk factors, there was no difference in the proportion of LBW (adjusted OR 0.92; IC95%, 0.37–2.25) between women having taken at least 2 SP doses and those with only one dose or none. Conclusion IPT‐SP remains an effective strategy in Kisangani and Mikalayi where the therapeutic failure to SP in children with clinical malaria was 21.7% and 1.6%, respectively, while IPTp‐SP effect seems lower in Rutshuru where the therapeutic failure to SP was 60.6%. The threshold value of SP resistance at which IPTp‐SP fails to have a significant impact on birth weight and LBW is unknown. Considering that no alternative is currently available, additional studies on the efficacy of IPTp‐SP in the areas of high SP resistance such as Rutshuru are needed so that the threshold at which this intervention fails to provide any benefit is determined with some precision.     

Accuracy of abdominal ultrasound and MRI for detection of Crohn disease and ulcerative colitis in children

Background

Endoscopy is currently the primary diagnostic technique for inflammatory bowel disease (IBD) in children.

Objective

To assess the accuracy of US and dynamic contrast-enhanced MRI for diagnosing inflammatory bowel disease and for distinguishing Crohn disease and ulcerative colitis in comparison to a reference standard.

Materials and methods

Consecutive children with suspected IBD underwent diagnostic workup including ileocolonoscopy and upper gastrointestinal endoscopy as the reference standard, abdominal US, and MR enterography and colonography at 3 T. The protocol included a dynamic contrast-enhanced 3-D sequence. Sensitivity, specificity and kappa values were calculated for one ultrasonographer and two MRI observers.

Results

We included 28 children (15 boys) with mean age 14 years (range 10–17 years). The diagnosis was IBD in 23 children (72%), including 12 with Crohn disease, 10 with ulcerative colitis and 1 with indeterminate colitis. For the diagnosis of inflammatory bowel disease the sensitivity was 55% for US and 57% (both observers) for MR entero- and colonography, and the specificity was 100% for US and 100% (observer 1) and 75% (observer 2) for MR entero- and colonography. Combined MRI and US had sensitivity and specificity of 70% and 100% (observer 1) and 74% and 80% (observer 2), respectively. With the addition of a dynamic contrast-enhanced MR sequence, the sensitivity increased to 83% and 87%. US and MRI could only distinguish between Crohn disease and ulcerative colitis when terminal ileum lesions were present.

Conclusion

US and MR entero- and colonography have a high accuracy for diagnosing inflammatory bowel disease in children but cannot be used to distinguish Crohn disease and ulcerative colitis.     

Protease‐activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model

Protease‐activated receptor‐2 (PAR‐2) is a G protein‐coupled receptor that functions as a cell‐surface sensor for coagulation factors and other proteases associated with the tumour microenvironment. Pancreatic cancer cells express high levels of PAR‐2 and activation of PAR‐2 may induce their proliferation and migration. Interestingly, however, PAR‐2 expression is increased in stroma‐rich pancreatic cancer regions, suggesting a potential role of PAR‐2 in the tumour microenvironment. Here, we assessed the importance of PAR‐2 in the stromal compartment by utilizing an orthotopic pancreatic cancer model, in which tumour cells are PAR‐2‐positive, whereas stromal cells are PAR‐2‐negative. We assessed tumour weight and volume and analysed proliferation and (lymph)angiogenesis both in vivo and in vitro. We show that genetic ablation of PAR‐2 from the stromal compartment inhibits primary tumour growth, which is accompanied by reduced vascularization in primary tumours and reduced in tube formation of vascular endothelial cells in vitro. In contrast to smaller primary tumours, the number of lymph node metastases was increased in PAR‐2‐deficient animals, which was accompanied by an increased number of lymphatic vessels. In vitro tube‐formation assays show that PAR‐2 does not inhibit the intrinsic tube‐forming capacity of lymphatic endothelial cells, but that PAR‐2 actually inhibits cancer cell‐induced tube formation. Overall, stromal PAR‐2 thus plays a dual role in pancreatic cancer development by potentiating primary tumour growth but limiting lymphangiogenesis and subsequent lymph node metastasis. Our data identify a novel role of PAR‐2 in the tumour microenvironment and pinpoint PAR‐2 as a negative regulator of lymphangiogenesis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Measurement properties of the Groningen Frailty Indicator in home-dwelling and institutionalized elderly people

ObjectivesTo enable prevention of poor outcome in elderly people, a valid instrument is required to detect individuals at high risk. The concept of frailty is a better predictor than age alone. The Groningen Frailty Indicator (GFI) has been developed to identify frailty. We assessed feasibility, reliability, and construct validity of the self-assessment version of the GFI.DesignCross-sectional.SettingCommunity-based.ParticipantsHome-dwelling and institutionalized elderly persons were included in the study (n = 353) who met the following inclusion criteria: persons 65 years and older who were able to fill out questionnaires.MeasurementsThe feasibility of the GFI was assessed by determining the proportion of missing values per item. The internal consistency reliability of the GFI was established by calculating the KR-20. Mann-Whitney and Kruskal-Wallis tests were applied to assess discrimination between specific subgroups (known group validity). Convergent and discriminant validity was assessed using Spearman Rank correlations between GFI and diseases and disorders, case complexity, and health care needs (INTERMED), life satisfaction (Cantril Ladder of Life), activities of daily living (Katz), quality of life (EQ-5D), and mental health (SF-36). Finally, we used multivariate regression analyses to evaluate the cutoff score of the GFI (<4 versus ≥4).ResultsA total of 296 (84%) of the participants completed all items of the GFI; the internal consistency was 0.68. The GFI yielded statistically significant GFI scores for subgroups (known group validity). The correlations for the convergent (range 0.45 to 0.61) and discriminant validity (range 0.08 to 0.50) were also as hypothesized. In contrast with nonfrail participants, frail older persons had higher levels of case complexity, disability, and lower quality of life and life satisfaction.ConclusionsThis study supports the feasibility, reliability, and validity of the self-assessment version of the GFI in home-dwelling and institutionalized elderly people.     

Thoracoscopic treatment of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in humans. The majority of patients with AF can function reasonably well on a daily basis with anti-arrhythmic drugs. A small proportion of patients with AF remain symptomatic despite anti-arrhythmic drugs. They might have an indication for invasive treatment for AF, such as endovascular catheter ablation (effective particularly in paroxysmal AF) or the Cox-Maze procedure (open heart surgery), in which the conductivity between the pulmonary veins and the left atrium is blocked. Hybrid thoracoscopic pulmonary vein isolation (VATS-PVI) is a new minimally invasive treatment for AF where the cardiothoracic surgeon and cardiologist work closely together. During this procedure the cardiologist performs electrophysiological measurements to verify whether the blockade of conductivity is successful. This approach has a success rate of 86% at a follow-up of 12 months.     

Long‐term survival after resection for non‐pancreatic periampullary cancer followed by adjuvant intra‐arterial chemotherapy and concomitant radiotherapy

BackgroundThere is no consensus regarding the optimal adjuvant treatment after resection of non‐pancreatic periampullary adenocarcinoma (NPPC; distal common bile duct, ampulla, duodenum).ObjectivesThe present study was conducted to evaluate the impacts on longterm survival and recurrence of adjuvant intra‐arterial chemotherapy (IAC) and concomitant radiotherapy (RT) in patients submitted to resection for NPPC or pancreatic ductal adenocarcinoma (PDAC) in a randomized controlled trial.MethodsA total of 120 patients with PDAC (n = 62) or NPPC (n = 58) were prestratified at a ratio of 1:1 for tumour origin and randomized. Half of these patients were treated with adjuvant IAC/RT and the other half were treated with surgery alone. Follow‐up was completed for all patients up to 5 years after resection or until death.ResultsThere was no survival benefit in either the whole group (primary endpoint) or the PDAC group after IAC/RT. In the NPPC group, longterm survival was observed in 10 patients in the IAC/RT group and five patients in the control group: median survival was 37 months and 28 months, respectively. The occurrence of liver metastases was reduced by IAC/RT from 57% to 29% (P = 0.038). Cox regression analysis revealed a substantial effect of IAC/RT on survival (hazard ratio: 0.44, 95% confidence interval 0.23–0.83; P = 0.011).ConclusionsThis longterm analysis shows that median and longterm survival were improved after IAC/RT in patients with NPPC, probably because of the effective and sustained reduction of liver metastases. The present results illustrate that NPPC requires an adjuvant approach distinct from that in pancreatic cancer and indicate that further investigation of this issue is warranted.     

Combined intravenous,topical and oral tranexamic acid administration in total knee replacement: Evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate

Background

The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism > 12 months ago was monitored specifically.