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The Astros recovered from a blown lead and walked off the Guardians 10-9 in extras from Houston.
Cleveland plated a run in the top of the 10th, but Victor Caratini's pinch-hit, two-run homer in the bottom half of the frame sealed the win for Houston.
Josh Naylor and Estevan Florial jacked three-run shots for the Guardians, who are still first in the AL Central at 19-and-10.
The three-game set continues tonight.