2 Minute Medicine Rewind September 12, 2016


Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes

Though there have been some concerns with regards to MRI use during pregnancy, more data on the long-term effects of this imaging modality on the fetus is needed. This retrospective cohort study aimed to analyze the long-term data of fetuses exposed to MRI imaging during the first trimester of pregnancy or were exposed to IV gadolinium contrast as part of an MRI at any point during the pregnancy. 1,424,505 deliveries were analyzed and, for those fetuses that received a first-trimester MRI, an adjusted risk difference of 4.7 per 1000 person-years (95% CI: -1.6 to 11) was found for stillbirth compared with the unexposed group. The study did not yield significant differences for this group when comparing other outcomes, such as hearing or vision loss and congenital anomalies. The group who received gadolinium had an adjusted risk difference of 45.3 per 1000 person-years (95% CI: 11.3 to 86.8) when examining the composite outcome of inflammatory, rheumatologic, or infiltrative skin condition, as well as an adjusted risk difference of 47.5 per 1000 person-years (95% CI: 9.7 to 138.2) for the outcome of stillbirths and neonatal deaths when compared to the unexposed group. This study concluded that MRI exposure during the first trimester was not associated with increased risk for the outcomes measured. However, gadolinium enhancement was associated with increased risks of stillbirth and neonatal death, as well as obtaining an inflammatory, rheumatologic, or infiltrative skin condition.

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea

Studies have shown the association between sleep apnea and adverse cardiovascular events. This study aimed to investigate continuous positive airway pressure (CPAP) as a means of preventing these adverse cardiovascular events in those with moderate-to-severe obstructive sleep apnea (OSA) who also have cerebrovascular or coronary artery disease (CAD). 2,717 individuals between the ages of 45 and 75 with OSA and CAD were randomized to receive usual care or usual care and CPAP treatment. The primary end point was either hospitalizations for unstable angina, transient ischemic attack, heart failure, or death due to stroke, myocardial infarction, or other cardiovascular causes. This end point was reached in 17% of those in the CPAP group and 15.4% of those receiving usual care, resulting in a hazard ratio of 1.1 (95% CI: 0.91 to 1.32, P = 0.34). However, CPAP did improve quality of life by significantly reducing snoring, sleepiness, and the number of apnea or hypopnea events per hour during sleep. The study concluded that CPAP did not improve cardiovascular outcomes in mild-to-moderate obstructive sleep apnea patients.

Adjunctive Everolimus Therapy for Treatment-Resistant Focal-Onset Seizures Associated with Tuberous Sclerosis (EXIST-3)

Everolimus, an mTOR inhibitor, has been used in the past as a treatment for benign tumors in those with tuberous sclerosis complex but, in this study, it is investigated for its utility as an adjuvant for treatment-resistant focal-onset seizures that are also a part of the tuberous sclerosis complex. This randomized, double blind study enrolled 366 patients between 2013 and 2015 and randomly assigned  patients to either receive placebo, a low dose of everolimus, or a high dose of everolimus. The response rates for the everolimus doses showed a significant difference with respect to placebo, with 40% responding to the high-dose (95% CI: 31.5 to 49%, P<0.0001), 28.2% responding to the low-dose (95% CI: 20.3 to 37.3%, P=0.0077), and 15.1% responding to placebo (95% CI: 9.2 to 22.8%). The percentage reduction in seizure frequency was also significantly higher for the everolimus treatment groups, as compared to placebo. However, serious adverse events were reported in 14% of those receiving either low or high-dose everolimus, as compared to 3% of patients receiving placebo. In those with treatment-resistant seizures from tuberous sclerosis complex, everolimus has a tolerable safety profile and significantly increased response rate.

Cord-Blood Transplantation in Patients with Minimal Residual Disease

Though siblings with HLA genes match are the best option for a hematopoietic-cell transplant, in many patients that is unavailable and, therefore, other types of donors are necessary. This retrospective analysis looked at outcomes of transplants from unrelated cord-blood donors, as well as unrelated, matched HLA donors and unrelated, unmatched HLA donors in 582 patients with acute leukemia or myelodysplastic syndrome. In those with minimal residual disease before transplantation, no significant difference was found between the HLA-matched group and the cord-blood group, with a hazard ratio of 1.68 (95% CI: 0.94 to 3.02, P=0.08). However, the risk of death was higher in the HLA-unmatched group when compared to the cord-blood group, with a hazard ratio of 2.92 (95% CI: 1.52 to 5.63, P=0.001). Additionally, risk of relapse was significantly higher in the unrelated HLA groups, as opposed to the cord-blood group. However, no significant differences were found among the groups in those without minimal residual disease present. This study showed that using cord-blood instead of unrelated HLA-matched or unmatched donors lowered the risk of relapse in those with minimal residual disease. The chances of survival are also better when cord-blood is used as opposed to an unrelated and unmatched donor and at least as good as compared to an unrelated, HLA-matched donor.

Combined Nivolumab and Ipilimumab Versus Ipilimumab Alone in Patients with Advanced Melanoma

Nivolumab, an anti-PD-1 antibody, and ipilimumab, an anti-CTLA-4 antibody, have shown promising results in phase 2 and 3 trials when used together to treat advanced melanoma. In this double blind, randomized trial, investigators assessed the 2-year survival data for this treatment, as compared to ipilimumab alone, in those with unresectable stage III or IV melanoma. 142 patients were assigned to receive four doses every 3 weeks of either ipilimumab and placebo or ipilimumab and nivolumab. Subsequently, the group that received both drugs received a phase of just nivolumab until there was unacceptable toxicity or progression of the melanoma, while the other treatment group received placebo alone. Survival rate at 2 years was 63.8% (95% CI: 53.3 to 72.6%) for the ipilimumab and nivolumab group while it was 53.6% for those who received ipilimumab alone (95% CI: 38.1 to 66.8%). Serious adverse events occurred in 36% of those receiving ipilimumab and nivolimumab and 9% of those receiving just ipilimumab. Though the incidence of adverse events increased, these results suggest the combination therapy has a positive impact on 2-year survival in untreated advanced melanoma, but further follow-up is needed and ongoing.

Image: PD

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