Immediate Weightbearing and Ankle Motion Exercise After Acute Achilles Tendon Rupture Repair.

The incidence of Achilles tendon rupture is increasing. Postoperative rehabilitation after repairing acute Achilles tendon rupture is very important because the choice of treatment during the rehabilitation period can influence the results. Moreover, the method of functional rehabilitation varies and is developing steadily. Recent studies recommend a functional rehabilitation protocol, and this approach is accepted widely. This study aimed to introduce our most accelerated functional rehabilitation protocol following surgery for acute Achilles tendon rupture and to review the results retrospectively. From July 2014 to July 2016, 67 patients underwent surgery for acute Achilles tendon rupture by one surgeon. Age, sex, body mass index, injury mechanism, rehabilitation method and progress, time to return to previous physical activity, and complications were evaluated. The mean time to be able to squat fully was 10 ± 4.7 (4-20) weeks. Full squatting was possible in 92.8% (52 patients). The mean time to perform a single-limb heel rise and repetitive single-limb heel rise was 12.6 ± 3.9 (6-24) and 23.3 ± 7.7 (8-40) weeks, respectively. The mean time to return to sports was 20.6 ± 5.2 (12-32) weeks. The major complication rate was 3.5% (one re-rupture and one tendon elongation). The mean pre- and postoperative Achilles Tendon Total Rupture Score was 29.5 ± 3.7 (20-38) and 79.3 ± 18.5 (20-98) points, respectively. The increase was significant (p < .01). In conclusion, immediate full weightbearing and ankle motion exercise after repair of acute Achilles tendon rupture can provide a good rehabilitation option with a low re-rupture rate and satisfactory functional results.

USP8 is a novel target for overcoming gefitinib resistance in lung cancer.

PURPOSE: Common treatment modalities for non-small cell lung cancer (NSCLC) involve the EGF receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib and erlotinib. However, the vast majority of treated patients acquire resistance to EGFR-TKIs, due, in large part, to secondary mutations in EGFR or amplification of the MET gene. Our purpose was to test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target for gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Testing the effect of knockdown of USP8 and use of a synthetic USP8 inhibitor to selectively kill gefitinib-resistant (or -sensitive) NSCLCs with little effect on normal cells in cell culture and a xenograft mouse model. RESULTS: Knockdown of ubiquitin-specific peptidase 8 (USP8) selectively kills gefitinib-resistant NSCLCs while having little toxicity toward normal cells. Genetic silencing of USP8 led to the downregulation of several receptor tyrosine kinases (RTK) including EGFR, ERBB2, ERBB3, and MET. We also determined that a synthetic USP8 inhibitor markedly decreased the viability of gefitinib-resistant and -sensitive NSCLC cells by decreasing RTK expression while having no effect on normal cells. Moreover, treatment with a USP8 inhibitor led to significant reductions in tumor size in a mouse xenograft model using gefitinib-resistant and -sensitive NSCLC cells. CONCLUSIONS: Our results show for the first time that the inhibition of USP8 activity or reduction in USP8 expression can selectively kill NSCLC cells. We propose USP8 as a potential therapeutic target for gefitinib-resistant and -sensitive NSCLC cells.