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World number five Alexander Zverev continued his poor recent form as he crashed out of the Italian Open in the second round while Serena Williams had to pull out of the women's draw with a recurring knee injury on Tuesday.
Serena had beaten Swede Rebecca Peterson in straight sets on Monday and was due to face sister Venus but the injury means her participation at the May 26-June 9 French Open is in doubt.
Zverev, who has not got past the quarter-finals at any tournament since reaching the Acapulco final in early March, did little to suggest he could be a contender at Roland Garros after a 7-5, 7-5 defeat by home favourite Matteo Berrettini.
Roared on by a partisan home crowd at the Foro Italico, Berrettini took the opening three games before the German, 2017 champion and last year's runner-up, regained his composure.
Berrettini then saved five break points to take a 6-5 lead before the rattled Zverev, who beat the Italian in the same round last year, threw away the opening set with two unforced errors and a double fault.
They traded breaks early in the second before Zverev, who saved a match point in the 10th game, committed another flurry of errors, capped by a forehand into the net that handed Berrettini a memorable win.
"The environment was great, the match that I played was horrendous," said the 22-year-old Zverev.
In first-round action, David Goffin produced two blistering sets to fight back and beat Stanislav Wawrinka 4-6, 6-0, 6-2 while Nick Kyrgios treated the crowd to an array of his antics in a 6-3, 3-6, 6-3 victory over Russian Daniil Medvedev.
The flamboyant and unpredictable Kyrgios again displayed his best and worst as he combined spectacular shots with an outburst of poor behaviour.
The Australian won the opening point of the match with what is fast becoming a trademark underarm serve and breezed through the first set before cheers from the crowd turned to jeers amid a second-set meltdown.
Having dropped serve to hand Medvedev a 5-3 lead, Kyrgios blasted a ball over the stands, then bent over and turned his backside to Medvedev and finally exchanged words with the umpire before the Russian held to force a third set.
As if nothing had happened, Kyrgios got back to business as he hammered in aces and winners, having also capped some good forays to the net with confident volleys to book a second-round clash with Norwegian Casper Ruud.
Goffin dropped the opening set before he blew Wawrinka away in the next two, the decisive moment coming in the second game of the third when the Belgian saved a double break point at 1-0 down.
He won the next five games and, although the Swiss briefly delayed the inevitable, Goffin was able to celebrate after his frustrated opponent blazed a forehand into the crowd.
Victoria Azarenka of Belarus knocked out holder Elina Svitolina 4-6, 6-1, 7-5 as she dug deep in a second-round evening match that was twice interrupted by rain in the second set.
Ukrainian fifth seed Svitolina appeared to be cruising in the third set as she served for the match at 5-2 up but the resilient Azarenka rallied to claim the last five games.
Ashleigh Barty had to work hard for a 4-6, 6-3, 6-4 win over Viktoria Kuzmova to reach the third round, while Kristina Mladenovic cruised past French compatriot Caroline Garcia 6-,1 6-2 in their first round clash.
The leading men get their campaigns underway on Wednesday when world number one Novak Djokovic, fresh from winning last week's Madrid Open, takes on Canadian Denis Shapovalov.
Holder Rafael Nadal faces Frenchman Jeremy Chardy, while Roger Federer meets Portugal's Joao Sousa.
Kyrgios again displayed his best and worst as he combined spectacular shots with an outburst of poor behaviour
Shapovalov earns Rome meeting with Djokovic
Canadian Denis Shapovalov set up a clash with World No 1 Novak Djokovic when he beat Pablo Carreno Busta in straight sets in his first round match at the Italian Open on Monday.
The 20-year-old, who last year became the youngest player to reach the top 30 since 2005, put a four-match losing streak behind him as he beat the Spaniard 6-3, 7-6(5).
France's 15th seed Gael Monfils lost 6-3, 6-1 to Spanish qualifier Albert Ramos-Vinolas, in 61 minutes.
Fernando Verdasco produced a remarkable comeback to beat Britain's Kyle Edmund 4-6, 6-4, 6-2. After losing the first set and trailing 4-1 in the second, the Spaniard won 10 games out of the next 13 to claim the victory.
Italian Fabio Fognini continued his progress towards breaking into the world's top 10 with a 6-3 6-4 win over Jo-Wilfried Tsonga. The 10th seed outmanoeuvred the Frenchman in baseline rallies to win in one hour and 23 minutes.
American Gibbs pulls out of French Open after cancer diagnosis
American Nicole Gibbs said on Monday she will miss the rest of the clay court season including this month's French Open after being diagnosed with a rare form of cancer.
The 26-year-old world number 116 said that about a month ago a dentist alerted her to a growth on the roof of her mouth and a biopsy revealed she had salivary gland cancer.
"Fortunately, this form of cancer has a great prognosis and my surgeon is confident that surgery alone will be sufficient treatment," she wrote on Twitter, adding that she will have surgery on Friday.
"He even okayed me to play an extra couple (of) tournaments these past few weeks which served as a nice distraction."
The Stanford University product said her goal was to be back for Wimbledon qualifying at the end of June.
"I am feeling extremely grateful for the UCLA health network that's been taking amazing care of me, and for rock solid friends and family who are helping me every step of the way," she said. "See you back on the court soon."
