Citations

BackgroundOptimal clinical trial endpoints for irritable bowel syndrome with constipation (IBS‐C) are uncertain.ObjectiveThe objective of this article is to compare adequate relief (AR) to abdominal/bowel symptoms, global endpoints, and FDA and EMA responder criteria; and to use AR as an anchor to assess clinically meaningful change (CMC) in IBS‐C symptoms.MethodsUsing pooled 12‐week data from two phase 3 linaclotide clinical trials, daily abdominal/bowel symptoms and weekly global assessments were correlated with AR. Symptom CMC thresholds were estimated using AR as an anchor. Agreement between AR and FDA/EMA responder criteria was assessed.ResultsCorrelations of AR with percentage change in abdominal symptoms, bowel symptoms, and global endpoints ranged from 0.48–0.54, 0.32–0.39, and 0.61–0.71, respectively. Using AR as an anchor, CMC thresholds were 29% improvement in abdominal pain, 29% improvement in abdominal discomfort, and 0.7/week increase in CSBMs, similar to thresholds for IBS‐C responder endpoints recommended by the FDA and EMA. There was considerable agreement of weekly responder rates between AR and the FDA and EMA endpoints (on average, 70%–76% and 71%–82% of weeks with agreement, respectively).ConclusionsAR bridges IBS‐C clinical trials, putting into perspective the disparate primary endpoints recommended by professional societies and regulatory authorities, and allowing researchers, practitioners, and regulators to compare trial results.

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic “starfield” pattern on MRI. This “starfield” MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis

Purpose Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) –positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2), was updated in 2011. We now report the planned definitive overall survival (OS) results from this joint analysis along with updates on the disease-free survival (DFS) end point. Methods In all, 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in both trials. The required number of events for the definitive statistical analysis for OS (710 events) was reached in September 2012. Updated analyses of overall DFS and related subgroups were also performed. Results Median time on study was 8.4 years. Adding trastuzumab to chemotherapy led to a 37% relative improvement in OS (hazard ratio [HR], 0.63; 95% CI, 0.54 to 0.73; P < .001) and an increase in 10-year OS rate from 75.2% to 84%. These results were accompanied by an improvement in DFS of 40% (HR, 0.60; 95% CI, 0.53 to 0.68; P < .001) and increase in 10-year DFS rate from 62.2% to 73.7%. All patient subgroups benefited from addition of this targeted anti-HER2 agent. Conclusion The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.

Background and purpose Mechanisms of both healing and complications, including spontaneous aneurysm rupture, remain unclear following flow diverter treatment. The aim of this study was to compare gene expression of various key molecules involved in the healing of aneurysms, between aneurysms treated with microcoils and flow diverters. Methods Saccular aneurysms were created in rabbits. Aneurysms were treated with coils (n=6) or flow diverters (n=6). Aneurysms were harvested at 4 weeks following treatment and used for gene expression and zymography experiments. Genes with a fold change of 1.2 or more were considered upregulated whereas those with a fold change of 0.8 or less were considered downregulated. Results All coil embolized aneurysms were completely occluded at follow-up. Two aneurysms were occluded and the remaining four samples were incompletely occluded in the flow diverter treated group. The following genes were expressed at lower levels in the flow diverter group compared with the coiled aneurysm group: proteinases (matrix metalloproteinases 2 and 9), cellular markers (endothelial nitric oxide synthase and smooth muscle actin), and structural proteins (collagens and fibronectin). Genes related to inflammation (tumor necrosis factor α and monocyte chemoattractant protein 1) were upregulated in flow diverter treated aneurysms compared with coil embolized aneurysms. Notably, the enzymatic activity of active matrix metalloproteinase 9 was high in aneurysms treated with flow diverters. Conclusions Our findings may provide improved understanding of rupture risk and healing following aneurysm treatment and inform development of therapies aimed at lowering rupture risk and accelerating healing.

Background The use of diagnostic and interventional ultrasound has significantly increased over the past decade. A majority of the increased utilisation is by non-radiologists. In sports medicine, ultrasound is often used to guide interventions such as aspirations, diagnostic or therapeutic injections, tenotomies, releases and hydrodissections. Objective Critically review the literature related to the accuracy, efficacy and cost-effectiveness of ultrasound-guided injections (USGIs) in major, intermediate and small joints; and soft tissues. Design Systematic review of the literature. Results USGIs are more accurate than landmark-guided injections (LMGIs; strength of recommendation taxonomy (SORT) Evidence Rating=A). USGIs are more efficacious than LMGIs (SORT Evidence Rating=B). USGIs are more cost-effective than LMGIs (SORT Evidence Rating=B). Ultrasound guidance is required to perform many new procedures (SORT Evidence Rating=C). Conclusions The findings of this position statement indicate there is strong evidence that USGIs are more accurate than LMGI, moderate evidence that they are more efficacious and preliminary evidence that they are more cost-effective. Furthermore, ultrasound-guided (USG) is required to perform many new, advanced procedures and will likely enable the development of innovative USG surgical techniques in the future.