Playoff contenders face off as the Detroit Lions take on the Buffalo Bills in a pivotal interconference matchup on Thursday Night Football. The game marks the opening of the new Highmark Stadium for Buffalo. The Lions, fresh off a thrilling 31-30 overtime victory against the New Orleans Saints, aim for their fifth consecutive winning season under coach Dan Campbell. Meanwhile, the Bills are looking to secure their eighth straight winning season, marking the first under coach Joe Brady.

Kickoff is scheduled for 8:15 p.m. ET in Orchard Park, N.Y. Buffalo enters the game as a 4.5-point favorite, with the over/under set at 54.5, the highest on the Week 2 NFL odds board.

Larry Hartstein, a renowned analyst with a strong track record, has been on a 22-11-1 roll with his last 34 picks involving the Lions, returning $966 to $100 players. Hartstein emphasizes the offensive firepower of both teams, noting:

• Jahmyr Gibbs led the Lions with 156 rushing yards and two touchdowns.
• Amon-Ra St. Brown caught 10 passes for 67 yards and two scores.
• Josh Allen threw for 334 yards and two touchdowns for the Bills.

Hartstein points out the Lions' defense, currently without safeties Kerby Joseph and Brian Branch, struggled in their last outing, being on the field for 86 plays. He warns that this fatigued unit will face a formidable challenge against the Bills, who recently defeated what many consider the NFL's top defense.

For those looking to make informed picks, Hartstein has identified a crucial X-factor that could influence the game’s outcome. Check out his insights at SportsLine.