2 Minute Medicine Rewind November 13, 2017

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct

Endovascular thrombectomy has been shown to have clinical benefit in patients with acute stroke when performed within 6 hours after the onset of stroke symptoms. However, it is unclear whether there is any clinical benefit if performed after 6 hours. In this randomized controlled trial, 206 patients with evidence of artery occlusion in the proximal middle cerebral artery (MCA) or intracranial internal carotid artery were randomized to thrombectomy (6 to 24 hours after stroke onset) plus standard medical care, or to standard medical care alone. Investigators examined the effect of thrombectomy on the primary outcome of disability at 90 days. Researchers found that the mean score for disability on the utility-weighted modified Rankin scale at 90 days was higher in the thrombectomy group in comparison to the control group (adjusted difference 2.0 points, 95% CI 1.1 to 3.0, posterior probability of superiority >0.999). Results also showed that the rate of functional independence was significantly greater in the thrombectomy group at 49% compared to 13% in the control group (adjusted difference 33%, 95% CI 24% to 44%, posterior probability of superiority >0.999). The rate of neurologic deterioration was also lower in the thrombectomy group compared to the control group (absolute difference -12%, 95% CI -23% to -1%, p=0.04). In terms of safety, at 90 days there was no significant difference between the groups in terms of number of stroke-related deaths, death from any cause, or symptomatic intracerebral hemorrhage. It is important to note that enrollment in the study was stopped at 31 months as the interim analysis showed a predictive probability of superiority of thrombectomy of at least 95% for the first primary end point. Overall, results from this study indicate that thrombectomy performed 6 to 24 hours after acute strokes are of clinical benefit in patients affected by acute stroke.. This trial, however, enrolled patients with infarcts of small or medium volume, and so the effect on thrombectomy on other patient populations requires further study.

A Test-and-Not-Treat Strategy for Onchocerciasis in Loa loa–Endemic Areas

The incidence of severe adverse events during the treatment of Loa loa infections with ivermectin appears to be related to the density of L. loa microfilarial loads. As such, researchers have proposed that excluding patients with high microfilarial loads could decrease the number of severe adverse events, including death. In this test-and-not-treat study, investigators used a mobile-telephone-based videomicroscope (LoaScope) to count L. loa microfilaria in the peripheral blood of 16,259 patients and exclude participants from ivermectin distribution based on high microfilarial load. Active surveillance for post-treatment adverse events was subsequently performed daily for 6 days. Out of the 16,259 participants, 340 individuals (2.1%) were excluded from ivermectin distribution due to a L. loa microfilarial density above the risk threshold, and another 397 (2.4% ) were excluded due to pregnancy or illness. Out of the 15,522 participants who received ivermectin, 934 (6.0%) experienced an adverse event, however, these events resolved within 1 week. There were no incident deaths or serious adverse events requiring hospitalization. Evaluation of the participants with adverse events for microfilaremia or presence of anti-Ov16 IgG4 antibodies showed that 43.2% had neither microfilaremia nor anti-Ov16 IgG4, and another 23.9% had only anti-Ov16 IgG4 antibodies. Compared to ivermectin distribution in 1999 that caused severe adverse events in 38 per 10,000 persons, the lack of severe adverse events from this study suggests that this test-and-not-treat strategy may be an acceptable strategy that could reduce the number of serious adverse events. This has important implications for communities where ivermectin-related serious adverse events have occurred in the past, leading to fear and non-participation.

Effect of Oral Administration of a Mixture of Probiotic Strains on SCORAD Index and Use of Topical Steroids in Young Patients With Moderate Atopic Dermatitis

Atopic dermatitis (AD), a chronic recurrent inflammatory skin disease, may be affected by gut microbiota that influence intestinal barrier function and immune modulation.  In this randomized controlled trial, investigators randomized 50 children with AD to a mixture of probiotics or placebo for 12 weeks in order to examine the effect on the Scoring Atopic Dermatitis (SCORAD) index as well as topical steroid use for flares. Researchers found that 96% of patients in the probiotic group had improvement in the SCORAD index compared to 46% in the placebo group at 12 weeks of follow-up. There was a larger mean change in SCORAD index of -83% in the probiotic group (95% CI -95% to -70%) in comparison to a change of -24% (95% CI -35% to -11%) in the placebo group (overall difference -59%, 95% CI -72% to -46%, p<0.001). A logistic regression showed that patients on probiotics were less likely to use topical steroids for flares than those on placebo (OR 0.63, 95% CI 0.51 to 0.78, p<0.001). Taken together, the results from this study support the efficacy of certain probiotics in treating AD in children.

Positron Emission Tomography/Computed Tomography–Based Assessments of Androgen Receptor Expression and Glycolytic Activity as a Prognostic Biomarker for Metastatic Castration-Resistant Prostate Cancer

Treatments targeting the androgen receptor (AR) have become more widely available as part of the management of prostate cancer. However, the role of biomarkers in determining which patients should receive AR is unclear. In this cohort study, investigators imaged 133 patients with metastatic castration-resistant prostate cancer (mCRPC) using dual positron emission tomography/computed tomography (PET/CT) imaging with 2-fluoro-2-deoxy-D-glucose F 18 ([¹⁸F]-FDG) as an indicator of tumor glycolysis and fluorodihydrotestosterone F18 ([¹⁸F]-FDHT) as an AR probe. Lesions were evaluated as [¹⁸F]-FDG and/or [¹⁸F]-FDHT positive allowing investigators to assess the association between imaging phenotypes and overall survival. Results from PET/CT imaging detected 2405 metabolically active lesions in 87.2% the patients. These patients were grouped into 4 categories based on whether patients had lesions that were all positive for both tracers (AR₁Glyc₁, 25.6% of patients), concordant for both tracers with predominance of [¹⁸F]-FDHT in at least one lesion (AR₁Glyc₁/AR₁Glyc₀, 24.8% of patients), patients with concordance of both tracers and predominance [¹⁸F]-FDG in at least one lesion (AR₁Glyc₁/AR₀Glyc_1, 30.1% of patients), and patients with a mixture of concordant lesions (mix, 19.5% of patients). Results showed that each of the three phenotypes of lesions had an independent negative impact on survival; AR₀Glyc₁ lesions had the most pronounced effect (HR 1.11, 95% CI 1.05 to 1.16, p<0.001), followed by AR₁Glyc₁ (HR 1.05, 95% CI 1.03 to 1.06, p<).001), and AR₁Glyc_{0 ­}lesions (HR 1.03; 95% CI 1.00 to 1.05; p=0.048). Overall, the results from this study indicate that heterogeneity of PET/CT imaging phenotype is of clinical relevance in patients with mCRPC in terms of prognosis, and could be used to guide choice of treatment. It is important to note, however, that there may have been other lesions in patients imaged since only two tracers were used, and the imaging field of view was limited. As such, more studies are needed to generalize the findings to all lesions.

Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years

Experimental cancer model systems have demonstrated the anti-tumor potential of warfarin, which is the most widely used anticoagulant in the world, although no large-scale cohort study has been conducted to date. In this population-based cohort study, investigators examined data for 1,256,725 individuals age 52 to 82 years old from the Norwegian National Registry in order to study the effect of warfarin use on rates of cancer. Of the entire cohort, 7.4% were classified as warfarin users. In general, warfarin users were treated for more than 2 years, predominantly men, and older than non-users (mean age 70.2 vs. 63.9). In comparison to nonusers, warfarin users had a significantly lower incident rate ratio (IRR) for all cancer sites (adjusted IRR 0.84, 95% CI 0.82 to 0.86). Warfarin users also had a significantly lower IRR for 3 out of the 4 most prevalent cancer sites: prostate (IRR 0.69, 95% CI 0.65 to 0.72), lung (IRR 0.80, 95% CI 0.75 to 0.86), and female breast cancer (IRR 0.90, 95% CI 0.82 to 1.00). There was no statistically significant difference in IRR for colon cancer. A subgroup analysis of patients with atrial fibrillation also showed that warfarin users had a significantly lower IRR for all cancer sites (IRR 0.62, 95% CI 0.59 to 0.65). Results from this cohort study suggest that warfarin use may be associated with a lower risk of cancer. These findings may have important implications in the selection of medications in patients requiring anticoagulation.

Image: PD

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