Some of mine are:
>Dwayne doesn't make it to Amateur Surgeon 4 and Alan outlives him
>Ophelia is in her late teens when she applies to be mentored by Alan. She isn't living with her parents because of some personal issues and is either with other relatives or in a foster home.
>Alan is still in high school in the first game, but he isn't a minor. He's a nineteen-year-old senior (or junior?) and was held back in school
>Doc Bleed (before Dwayne showed up) had been a renowned surgeon in a different city but ran off to Bleedmore to escape the shame of being "responsible" for the deaths that he didn't know Dwayne had caused
*Bonus to the last, Aureola's parents are from Bleedmore and had traveled to Bleed's hometown to receive surgery from him. I like to think she was young at the time, maybe a year younger (or older) than Alan would have been.