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Napoli crashed out of the Europa League in the round of 32 despite a 1-0 win away to RB Leipzig on Thursday.
Lyon proved to be too much for Villarreal over two legs as they ran out 4-1 aggregate winners and advanced to the Europa League round of 16.
Diego Simeone's Atletico Madrid cruised to the Europa League round of 16 as they defeated Copenhagen 5-1 on aggregate.
Henrikh Mkhitaryan has told ESPN FC that Arsenal can secure Champions League qualification without having to rely on Europa League success.
Napoli head coach Maurizio Sarri remains confident the Serie A leaders can overturn a 3-1 deficit as they prepare to face Leipzig in the second leg of their last 32 Europa League tie in Germany.