Bevacizumab for the treatment of high-grade glioma

Introduction: Gliomas are highly vascular and rich in vascular endothelial growth factor (VEGF) that promotes angiogenesis. Bevacizumab is a monoclonal antibody against VEGF inhibiting angiogenesis by preventing receptor activation. Phase II clinical trials using bevacizumab in both newly diagnosed and recurrent high-grade glioma (HGG) showed promising results.

Areas covered: This is a review of clinical trials investigating bevacizumab in newly diagnosed and recurrent HGGs with a focus on outcome results. A future perspective about the expected role of bevacizumab is given. Bevacizumab efficacy, safety and tolerability, the combination of radiation and bevacizumab as well as the use of bevacizumab to treat pseudoprogression are discussed. Further criteria of response evaluation needed to be adjusted in the age of anti-angiogenic therapy and this will be discussed.

Expert opinion: Bevacizumab has been shown to be safe and tolerable in HGG. In the recurrent disease setting, bevacizumab alone might be sufficient for a clinical benefit and is currently approved as a single agent for this indication. While clinical trials demonstrate a prolonged progression-free survival in bevacizumab-treated HGG, a benefit on OS has not been demonstrated yet. Bevacizumab has also been introduced into other settings in neuro-oncology including concurrent administration with re-irradiation for recurrent HGG.

Best practice for prevention and treatment of cardiovascular disease through an equity lens : a review

Background Despite declining rates of cardiovascular disease (CVD) mortality in developed countries, lower socioeconomic groups continue to experience a greater burden of the disease. There are now many evidence-based treatments and prevention strategies for the management of CVD and it is essential that their impact on the more disadvantaged group is understood if socioeconomic inequalities in CVD are to be reduced.

Aims To determine whether key interventions for CVD prevention and treatment are effective among lower socioeconomic groups, to describe barriers to their effectiveness and the potential or actual impact of these interventions on the socioeconomic gradient in CVD.

Methods Interventions were selected from four stages of the CVD continuum. These included smoking reduction strategies, absolute risk assessment, cardiac rehabilitation, secondary prevention medications, and heart failure self-management programmes. Electronic searches were conducted using terms for each intervention combined with terms for socioeconomic status (SES).

Results Only limited evidence was found for the effectiveness of the selected interventions among lower SES groups and there was little exploration of socioeconomic-related barriers to their uptake. Some broad themes and key messages were identified. In the majority of findings examined, it was clear that the underlying material, social and environmental factors associated with disadvantage are a significant barrier to the effectiveness of interventions.

Conclusion Opportunities to reduce socioeconomic inequalities occur at all stages of the CVD continuum. Despite this, current treatment and prevention strategies may be contributing to the widening socioeconomic-CVD gradient. Further research into the impact of best-practice interventions for CVD upon lower SES groups is required.

Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.

Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.

Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p < 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.

Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.

Improving the identification and treatment of depression in women after acute myocardial infarction

We read with interest the article by Smolderen et al (1), which reported real-world lessons from the implementation of an American Heart Association (AHA) recommended depression screening protocol in Acute Myocardial Infarction (AMI) patients. After implementing a routine, two- step depression screening process using the Patient Health Questionnaire (PHQ) 2 and 9, the study revealed that more than 1 in 4 (n=135, 26.8%) Coronary Artery Disease (CAD) patients failed to be screened for depression. Specifically, women were likely to be missed. Of those who were screened, almost 7 of 10 patients with significant depressive symptoms failed to be recognized and thus were ineligible for treatment.

Treatment of ametryn in wastewater by a hybrid MBR system : a lab-scale study

Agricultural discharge of herbicides to the Great Barrier Reef (GBR) poses significant threat to the marine ecosystem. This study evaluates the performance of a hybrid treatment system consists of a membrane bioreactor (MBR), UV disinfection unit and a granular activated carbon (GAC) column in treating ametryn which is one of the major herbicides in agricultural discharges. While the MBR alone removes only 40% of ametryn at a hydraulic retention time of 7.8 h, the hybrid system removed ametryn to below detection levels.

Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.

Evaluation of the giant reed (Arundo donax) in horizontal subsurface flow wetlands for the treatment of dairy processing factory wastewater

Two emergent macrophytes, Arundo donax and Phragmites australis, were established in experimental horizontal subsurface flow (HSSF), gravel-based constructed wetlands (CWs) and challenged by treated dairy processing factory wastewater with a median electrical conductivity of 8.9 mS cm−1. The hydraulic loading rate was tested at 3.75 cm day−1. In general, the plants grew well during the 7-month study period, with no obvious signs of salt stress. The major water quality parameters monitored (biological oxygen demand (BOD), suspended solids (SS) and total nitrogen (TN) but not total phosphorus) were generally improved after the effluent had passed through the CWs. There was no significance different in removal efficiencies between the planted beds and unplanted gravel beds (p > 0.007), nor was there any significant difference in removal efficiencies between the A. donax and P. australis beds for most parameters. BOD, SS and TN removal in the A. donax and P. australis CWs was 69, 95 and 26 % and 62, 97 and 26 %, respectively. Bacterial removal was observed but only to levels that would allow reuse of the effluent for use on non-food crops under Victorian state regulations. As expected, the A. donax CWs produced considerably more biomass (37 ± 7.2 kg wet weight) than the P. australis CWs (11 ± 1.4 kg wet weight). This standing crop equates to approximately 179 and 68 tonnes ha−1 year−1 biomass (dry weight) for A. donax and P. australis, respectively (assuming a 250-day growing season and single-cut harvest). The performance similarity of the A. donax and P. australis planted CWs indicates that either may be used in HSSF wetlands treating dairy factory wastewater, although the planting of A. donax provides additional opportunities for secondary income streams through utilisation of the biomass produced.