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Wales flanker Ellis Jenkins will require surgery after being hurt during the dying seconds of last Saturday's victory over South Africa.
Jenkins' regional team Cardiff Blues confirmed that he suffered "a significant knee injury" as Wales beat the Springboks 20-11 in Cardiff.
In a statement, the Blues said: "Cardiff Blues can confirm Ellis Jenkins sustained a significant knee injury during Wales' autumn victory over South Africa, which will require surgical intervention.
"Further specialist reviews are needed to establish an accurate prognosis following surgery.
"Cardiff Blues and WRU (Welsh Rugby Union) have and will continue to work closely to manage Ellis's care optimally.
"No further comments will be made at this stage."
No timescale has so far been put on the 25-year-old's recovery, but it would appear that Jenkins is facing a lengthy lay-off.
Such an absence would potentially rule him out of the Six Nations and possibly the rest of this season, although it is just under nine months until Wales' opening World Cup warm-up game against England, while their first World Cup fixture is against Georgia on September 23.
Jenkins, who has won 11 caps and skippered Wales to victory over the Springboks earlier this year, received a late call-up off the bench to start after Dan Lydiate withdrew through injury.
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Chris Ashton's international comeback has stalled after the England wing was ruled out of Saturday's climax to the autumn series against Australia by a calf problem.
Ashton will be limited to three appearances this month due to the injury sustained in the 35-15 victory over Japan at Twickenham, a scan confirming that he will be sidelined for a fortnight.
The 31-year-old became available for England once more when he left Toulon for Sale over the summer and Eddie Jones immediately selected him in his squad for the Quilter Internationals.
When Manu Tuilagi was ruled out of the opener against South Africa because of a groin strain, he was cleared to win his 40th cap and first in over four years.
"Chris Ashton was hurt in the game on Saturday," forwards coach Steve Borthwick said.
"He's been scanned and investigated and unfortunately the injury means he will be out for a couple of weeks. He'll leave camp today (Tuesday).
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Nathan Hughes is poised to make his England comeback in Saturday's autumn finale against Australia after completing his six-week ban.
Hughes missed the opening three Quilter Internationals after being suspended for punching and conduct prejudicial to the interest of the game, the latter charge incurred for tweeting "what a joke" at the disciplinary process.
The Fijian-born Wasps forward is likely to be involved in the matchday 23 named by Eddie Jones on Thursday and will supply a ball-carrying threat at number eight where Mark Wilson and Zach Mercer have been providing cover.
Mercer has made way to accommodate Hughes' return among the 28 summoned to England's Surrey training base to prepare for Australia's visit.
Also axed after Saturday's laboured 35-15 victory over Japan are scrum-half Danny Care and centre Alex Lozowski.
Richard Wigglesworth, a second-half replacement on Saturday, will deputise for Ben Youngs from the bench against Australia after ousting Care, who has been jettisoned despite scoring the opening try.
Lozowski has paid the price for waving centre Ryoto Nakamura through under the posts for one of Japan's two touch downs, a mistake that saw him replaced by Owen Farrell at half-time.
The Saracen's removal opens the door to Piers Francis, who won the most recent of his four caps as a second-half replacement in the first Test of the summer tour to South Africa.
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