But he has seemingly been able to put the controversy behind him, manoeuvring his way through tough tests against Britain's Jack Draper and 2021 champion Medvedev.
"My aunt is not feeling well health-wise and I don't know how much longer I have her in my life," he said.
The 26-year-old recovered well to win three games in a row, but he continued to falter on serve and Sinner capitalised to take the opener and subdue the expectant mood on Arthur Ashe Stadium.
"If there was a wish I could make, I would wish good health on everyone but unfortunately it's not possible."
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Refusing to dwell on the first set, Fritz improved and made the second a closer affair, losing just two points in four service games.
It was more straightforward in New York as he rarely looked troubled by Fritz, who struggled to build any momentum.
Junto a todas las novedades comunicadas por la competición o presente sábado, de que pelo son pocas, la del fichaje por Lamine Yamal encumbra el arranque de una nueva temporada en la que se espera seguir creciendo.
Having failed to make the most of three break point opportunities early in the third set, Fritz brought the crowd to life with two brilliant winners to break for a 4-3 lead and keep alive his hopes.
It has been nearly 50 years since a man won their first and second Grand Slam titles in the same season, and Sinner is now a long way clear of the rest at the top of the rankings.
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Just six days before the main draw got under way, it was announced he had twice tested positive for low levels of a metabolite of clostebol - a steroid that can be used to build muscle mass - in March.
It marks a new era of tennis as 24-time major winner Novak Djokovic, who was knocked out in the third round, ends the year without a Grand Slam title for the first time since 2017.
He subsequently parted ways with the physio and his fitness trainer - but questions continued about whether Sinner's case had been handled differently to those of other players because of his world number one status.
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"He's stepped up a role and I feel like he's taking everything as seriously as he can and fair play to him, that shows he wants to stay."
"I know we have been waiting for a champion for a long time so I'm sorry I couldn't get it done this time," said Fritz.