Reversible posterior leukoencephalopathy syndrome in a child treated with bevacizumab

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Hypertension is a well‐recognized, common side effect of VEGF blocking agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been described as a rare but serious consequence of bevacizumab administration. We present a case of a 6‐year‐old child with refractory hepatoblastoma who developed hypertensive crisis, seizures and MRI changes consistent with RPLS while receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely resolved without neurologic sequelae with stringent blood‐pressure control. Better understanding of risk for RPLS, prompt recognition and aggressive management will be required as bevacizumab gains wider use in pediatrics. Pediatr Blood Cancer 2009;52:669–671. © 2008 Wiley‐Liss, Inc.     

Palliative care in gynaecological oncology

Gynaecological malignancy accounts for significant patient morbidity and mortality. Clinical aims focus upon palliative management and supportive care when potentially curative treatment options are exhausted. Patients with recurrent, advancing or terminal disease may suffer severe and distressing physical and psychological effects associated with both cancer diagnosis and treatments. It is of paramount importance that patients, families and carers are provided with the assistance they need to have as high a quality of life as possible.This review focuses upon the provision of relief from pain and other distressing symptoms commonly associated with gynaecological malignancy. In addition, we highlight some of the important aspects of psychosocial care.     

Can online benchmarking increase rates of thrombolysis? Data from the Austrian stroke unit registry

Despite its widespread availability and known safety and efficacy, a therapy with intravenous thrombolysis is still undergiven. We aimed to identify whether nationwide quality projects—like the stroke registry in Austria—as well as online benchmarking and predefined target values can increase rates of thrombolysis. Therefore, we assessed 6,394 out of 48,462 patients with ischemic stroke from the Austrian stroke registry (study period from March 2003 to December 2011) who had undergone thrombolysis treatment. We defined lower level and target values as quality parameters and evaluated whether or not these parameters could be achieved in the past years. We were able to show that rates of thrombolysis in Austria increased from 4.9 % in 2003 to 18.3 % in 2011. In a multivariate regression model, the main impact seen was the increase over the years [the OR ranges from 0.47 (95 % CI 0.32–0.68) in 2003 to 2.51 (95 % CI 2.20–2.87) in 2011). The predefined lower and target levels of thrombolysis were achieved at the majority of participating centers: in 2011 the lower value of 5 % was achieved at all stroke units, and the target value of 15 % was observed at 21 of 34 stroke units. We conclude that online benchmarking and the concept of defining target values as a tool for nationwide acute stroke care appeared to result in an increase in the rate of thrombolysis over the last few years while the variability between the stroke units has not yet been reduced.     

Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy

Alcohol-related acute pancreatitis can be mediated by a combination of alcohol and fatty acids (fatty acid ethyl esters) and is initiated by a sustained elevation of the Ca²⁺ concentration inside pancreatic acinar cells ([Ca²⁺]_i), due to excessive release of Ca²⁺ stored inside the cells followed by Ca²⁺ entry from the interstitial fluid. The sustained [Ca²⁺]_i elevation activates intracellular digestive proenzymes resulting in necrosis and inflammation. We tested the hypothesis that pharmacological blockade of store-operated or Ca²⁺ release-activated Ca²⁺ channels (CRAC) would prevent sustained elevation of [Ca²⁺]_i and therefore protease activation and necrosis. In isolated mouse pancreatic acinar cells, CRAC channels were activated by blocking Ca²⁺ ATPase pumps in the endoplasmic reticulum with thapsigargin in the absence of external Ca²⁺. Ca²⁺ entry then occurred upon admission of Ca²⁺ to the extracellular solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A, inhibited store-operated Ca²⁺ entry in a concentration-dependent manner within the range of 1 to 50 μM (IC₅₀ = 3.4 μM), but had little or no effect on the physiological Ca²⁺ spiking evoked by acetylcholine or cholecystokinin. Palmitoleic acid ethyl ester (100 μM), an important mediator of alcohol-related pancreatitis, evoked a sustained elevation of [Ca²⁺]_i, which was markedly reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced trypsin and protease activity as well as necrosis were almost abolished by blocking CRAC channels. There is currently no specific treatment of pancreatitis, but our data show that pharmacological CRAC blockade is highly effective against toxic [Ca²⁺]_i elevation, necrosis, and trypsin/protease activity and therefore has potential to effectively treat pancreatitis.     

Tipping the Scales: How Defendant Body Type May Result in Eyewitness Biases

Body type is often overlooked as a basis for discrimination and has rarely been examined in legal contexts. The present research examined the role of body type on eyewitness line-up misidentification. Participants watched a video of a violent crime or theft and were asked to select the defendant out of a suspect-absent line-up. The lineup included digitally altered photos displaying muscular, normal weight, and overweight defendants. Muscular defendants were most likely to be mistakenly selected out of the simultaneous line-up, and overweight defendants were least likely to be selected. These results indicate that body type may be a biasing factor in comparative eyewitness evaluations.     

Time‐lapse imaging points towards a non‐toxic,mainly immune‐driven mode of action of ingenol mebutate in the treatment of anogenital warts

Recently, it has been reported that ingenol mebutate (IM) is an effective treatment option for anogenital warts (AGW), inducing fast wart necrosis within 24 hours in vivo. With regard to its mode of action, IM is thought to act both as an inducer of direct cytotoxic effects and immunologic mechanisms. To distinguish whether the wart necrosis is mainly caused by cytotoxic effects, or whether immune mechanisms are leading, we used time‐lapse imaging to analyse IM‐treated warts ex vivo over 24 hours. Ex vivo IM‐treated warts, which have been detached from the immune system, did not show destructive necrosis, pointing towards a primarily immune‐driven mode of action of IM in the treatment of AGW.     

The Role of Supported Joint Engagement and Parent Utterances in Language and Social Communication Development in Children with Autism Spectrum Disorder

This study examined associations between three parent–child engagement states and social communication, expressive language, and receptive language at 8 month follow-up, in 63 preschool-age children with autism spectrum disorder. We extend the literature on supported joint engagement by dividing this state into higher order (HSJE) and lower order types, with HSJE involving greater reciprocity in toy play. We also examined parents’ follow-in utterances that co-occurred with each state. We found that only HSJE predicts later social communication and expressive language, while object engagement predicts receptive language. HSJE combined with follow-in utterances (HSJE+FI) predicts all three outcomes when controlling for HSJE+FI in other engagement states. When controlling for total HSJE, HSJE+FI is predictive of receptive language.