Hello,
I don’t know if it’s the same issue but I’ve noticed noise too , especially with my mutli-effect. I’m using an alesis io dock. The noise disapears if I close the power of the alesis dock, leaving cubasis, letting the multi effect (or your guitar cable) cable on and repower the dock and reopen cubasis. Maybe you should try that , or try the opposite (closing the multieffect and letting cubasis open at the same time).
For the 16-bit, i’ve made my first mixdown, transform it to aac, and i found the sound’s very good, close to my old tascam cp-24, which is 24 bit.
Good luck!