2 Minute Medicine Rewind June 12, 2017

Complete Dissection or Observation for Sentinel-Node Metastasis in Melanoma

The pathological status of the sentinel node, gathered via biopsy, is the most important prognostic factor in melanoma. This study aims to examine melanoma-specific 3-year survival, as it relates to complete lymph-node dissection versus observation in patients who are positive for metastasis to the sentinel node. In this randomized controlled trial, 1934 patients with sentinel node metastases were randomly assigned to undergo either lymph-node dissection or observation using ultrasound. As a greater proportion of patients assigned to complete lymph node dissection declined their assigned treatment, the authors reported on the results of their per-protocol analysis. Investigators found that survival rates were similar between the two groups, with a melanoma-specific survival rate of 86% (SE 1.3%) for the dissection group and 86% (SE 1.2%) for the observation group (p=0.42) at a median follow-up of 43 months. The rate of disease-free survival at 3 years of follow-up, however, was slightly greater in the dissection group at 68% (SE 1.7%) compared to the observation group at 63% (SE 1.7%) (p=0.05), likely attributable to an increased rate of disease of disease control in regional nodes in the intervention group at 92% (SE 1.0%) compared to 77% (SE 1.5%) in the observation group (p<0.001). This study therefore shows that while regional disease control may result in significantly greater with complete lymph node dissection, it does not confer a significant increase in melanoma-specific survival compared to observation alone in melanoma patients with sentinel node metastasis.

Incretin Based Treatments and Mortality in Patients with Type 2 Diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are incretin-based treatments frequently used in the management of type 2 diabetes. This systematic review and meta-analysis aimed to investigate the effects of these treatments on all-cause mortality, as compared to placebo and other anti-diabetic agents. Data from 189 randomized controlled trials including 155,419 patients, all determined to have low-to-moderate risk of bias, were compiled and analyzed. Researchers found that there was no significant difference in all-cause mortality between those receiving incretin-based therapy versus control medications (OR 0.96, 95% CI 0.90 to 1.02). However, investigators did suggest that further studies into the effect of GLP1 agonists alone or DPP4 inhibitors alone may be warranted, as there appeared to be some significant effect on mortality when comparing patients that had been treated with GLP1 agonists alone (OR 0.89, 95% CI, 0.80 to 0.99) to the control group. In summary, no significant effects on all-cause mortality were observed in patients using incretin-based drugs as compared to placebo or other anti-diabetic agents.

Brentuximab Vedotin or Physician’s Choice in CD30-Positive Cutaneous T-cell Lymphoma (ALCANZA)

Brentuximab vedotin, an anti-CD30 antibody, has previously been used in the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. In this multicenter randomized controlled trial, 131 patients across 52 centers in 13 countries were assigned to receive either IV brentuximab vedotin (1.8 mg/kg once every three weeks for up to 16 cycles) or receive the physician’s choice of either oral methotrexate (5-50 mg once per week) or oral bexarotene (300 mg/m2 once per day) in order to investigate the efficacy and safety of brentuximab vedotin in the treatment of CD30-positive cutaneous T-cell lymphoma. Results showed that, at a median follow up of 22.9 months, there was a significantly higher rate of global response lasting at least 4 months in the brentuximab vedotin group, yielding a between-group difference of 43.8%  (95% CI 29.1 to 58.4%, p<0.0001). Adverse event rates were similar between the two groups, with grade 3-4 events being reported in 41% of patients receiving brentuximab vedotin and 47% of patients in the physician’s choice group. However, there was one treatment-related death in the brentuximab group and none in the physician’s choice group. In summary, brentuximab vedotin was associated with a higher rate of patients achieving a global response lasting at least 4 months, as compared to oral methotrexate or oral bexarotene.

Early Goal-Directed Therapy for Septic Shock

Early goal-directed therapy (EGDT) is a treatment strategy for septic shock that includes the administration of IV fluids, inotropes, vasopressors, and red-cell transfusion aimed at achieving target values in arterial blood pressure and other measures. This meta-analysis aimed to compile data comparing EGDT to standard care in terms of the effect on mortality at 90 days in patients with septic shock. Data from 3,723 patients across seven countries was analyzed. It was found that EDGT did not result in a statistically significant improvement in 90-day mortality (OR 0.97, 95% CI 0.82 to 1.14, p=0.68) when compared to standard care. There was also no significant difference in survival at 1 year (HR 0.98, 95% CI 0.86 to 1.11, p=0.75). No statistically significant difference was found in subgroup analyses of patients with higher serum lactate, higher predicted risk of death, or patients with high serum lactate and hypotension. This study therefore shows that early goal-directed therapy does not lead to superior outcomes at 90-days of follow-up in patients with septic shock.

Moderate Alcohol Consumption as Risk Factor for Adverse Brain Outcomes and Cognitive Decline

The long-term effects of moderate alcohol consumption on the brain are currently unknown. In this cohort study, weekly alcohol intake and cognitive performance were measured repeatedly over the course of 30 years in 550 non-alcoholic men (median age of 43 (SD 5.4)) to investigate if there is an association between moderate alcohol use and both structural and functional brain measures. Magnetic resonance imaging (MRI) was performed at study endpoint. Researchers found that men consuming more than 30 units (1 unit = 10 mL) of alcohol per week had an increased risk of hippocampal atrophy, (OR 5.8, 95% CI 1.8 to 18.6, p≤0.001) as compared to those who did not consume alcohol. Those drinking between 14 and 21 units per week also had an increased risk of hippocampal atrophy (OR of 3.4, 95% CI 1.4 to 8.1, p=0.007) when compared to those who abstained. Increased alcohol consumption was also associated with faster decline in lexical fluency tests. As such, the investigators were able to conclude that moderate alcohol consumption is associated with adverse changes in the brain, specifically hippocampal atrophy.

Image: PD

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