ABSTRACT
The role for PD-1/PD-L1 and CTLA-4 targeted immunotherapy is well outlined in the treatment of metastatic NSCLC. Increased survival benefit supports the use of these medications and the development of next-generation agents with improved efficacy and favorable side-effect profiles. The prevalence of immunotherapy-associated cardiotoxicity (IAC) has grown significantly over the past two years as awareness of this toxicity class has emerged. High-grade conduction disorders comprise a subset of cardiotoxicities with a high case fatality rate. We presented a case of suspected combination ipilimumab-nivolumab associated 3rd degree heart block. The onset of this event was 16 days after immunotherapy initiation. A literature review has suggested that over 75% of cases of cardiotoxicity are observed within the first 6 weeks. We present findings from an interrogation of the FDA Adverse Event Reporting System (FAERS) and provide clinical guidance for the early identification of high-risk patients.
ABSTRACT
Magnesium, the second most abundant intracellular cation, is essential in many intracellular processes and appears to play an important role in migraine pathogenesis. Routine blood tests do not reflect true body magnesium stores since <2% is in the measurable, extracellular space, 67% is in the bone and 31% is located intracellularly. Lack of magnesium may promote cortical spreading depression, hyperaggregation of platelets, affect serotonin receptor function, and influence synthesis and release of a variety of neurotransmitters. Migraine sufferers may develop magnesium deficiency due to genetic inability to absorb magnesium, inherited renal magnesium wasting, excretion of excessive amounts of magnesium due to stress, low nutritional intake, and several other reasons. There is strong evidence that magnesium deficiency is much more prevalent in migraine sufferers than in healthy controls. Double-blind, placebo-controlled trials have produced mixed results, most likely because both magnesium deficient and non-deficient patients were included in these trials. This is akin to giving cyanocobalamine in a blinded fashion to a group of people with peripheral neuropathy without regard to their cyanocobalamine levels. Both oral and intravenous magnesium are widely available, extremely safe, very inexpensive and for patients who are magnesium deficient can be highly effective. Considering these features of magnesium, the fact that magnesium deficiency may be present in up to half of migraine patients, and that routine blood tests are not indicative of magnesium status, empiric treatment with at least oral magnesium is warranted in all migraine sufferers.
