After Dean was done talking to the "drunken woman", as Sam and him drove away from the "pirate eating establishment", the word "BITCH" can be seen, written in dust on the passenger side window of the car.
This is the first episode since the Season 9 finale to not feature Mark Sheppard (Crowley) as a series regular.
During the "Then and Now" recap from season 12, the song is "Nothing Else Matters," by Metallica. There has been numerous mentions and references throughout the seasons, but this is the first time a song of Metallica's is used.
Jack is not the first Nephilim to be featured on Supernatural; in Clip Show (2013), Castiel kills the Nephilim Jane in order to help Metatron close the gates of Heaven, not knowing that Metatron lied about his true reasons for her needing to die.
Dean refers to Jack as Damien, the name of the Anti-Christ (son of the Devil) in the classic horror movie, The Omen (1976)