The antifibrinolytic and anti-inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial. J Thromb Haemost 2018; 16: 2442-53. maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible. A B C D Fig. 4. Postoperative clinical outcomes.Patient-rated pain with 45°knee flexion (A) and at rest (B), knee circumference (local inflammation) (C) and range of motion (ROM) (D) after total knee arthroplasty. *Significantly different (P < 0.05) between groups A and B. †Significantly different (P < 0.05) between groups A and C. ‡Significantly different (P < 0.05) between groups A and D. §Significantly different (P < 0.05) between groups A and E. ¶Significantly different (P < 0.05) between groups B and C. **Significantly different (P < 0.05) between groups B and D. † †Significantly different (P < 0.05) between groups B and E. ‡ ‡Significantly different (P < 0.05) between groups C and D. § §Significantly different (P < 0.05) between groups C and E. ¶ ¶Significantly different (P < 0.05) between groups D and E. POD, postoperative day. [Color figure can be viewed at wileyonlinelibrary.com]

Femoral nerve blocks (FNB) can provide effective pain relief but result in quadriceps weakness with increased risk of falls following total knee arthroplasty (TKA). Adductor canal block (ACB) is a relatively new alternative providing pure sensory blockade with minimal effect on quadriceps strength. The meta-analysis was designed to evaluate whether ACB exhibited better outcomes with respect to quadriceps strength, pain control, ambulation ability, and complications. PubMed, Embase, Web of Science, Wan Fang, China National Knowledge Internet (CNKI) and the Cochrane Database were searched for RCTs comparing ACB with FNB after TKAs. Of 309 citations identified by our search strategy, 12 RCTs met the inclusion criteria. Compared to FNB, quadriceps maximum voluntary isometric contraction (MVIC) was significantly higher for ACB, which was consistent with the results regarding quadriceps strength assessed with manual muscle strength scale. Moreover, ACB had significantly higher risk of falling versus FNB. At any follow-up time, ACB was not inferior to FNB regarding pain control or opioid consumption, and showed better range of motion in comparison with FNB. ACB is superior to the FNB regarding sparing of quadriceps strength and faster knee function recovery. It provides pain relief and opioid consumption comparable to FNB and is associated with decreased risk of falls.

Here we tested anti-tumor activity of KU-0060648 in preclinical hepatocellular carcinoma (HCC) models. Our results demonstrated that KU-0060648 was anti-proliferative and pro-apoptotic in established (HepG2, Huh-7 and KYN-2 lines) and primary human HCC cells, but was non-cytotoxic to non-cancerous HL-7702 hepatocytes. DNA-PKcs (DNA-activated protein kinase catalytic subunit) is an important but not exclusive target of KU-0060648. DNA-PKcs knockdown or dominant negative mutation inhibited HCC cell proliferation. On the other hand, overexpression of wild-type DNA-PKcs enhanced HepG2 cell proliferation. Importantly, KU-0060648 was still cytotoxic to DNA-PKcs-silenced or -mutated HepG2 cells, although its activity in these cells was relatively weak. Further studies showed that KU-0060648 inhibited PI3K-AKT-mTOR activation, independent of DNA-PKcs. Introduction of constitutively-active AKT1 (CA-AKT1) restored AKT-mTOR activation after KU-0060648 treatment in HepG2 cells, and alleviated subsequent cytotoxicity. In vivo, intraperitoneal (i.p.) injection of KU-0060648 significantly inhibited HepG2 xenograft growth in nude mice. AKT-mTOR activation was also inhibited in xenografted tumors. Finally, we showed that DNA-PKcs expression was significantly upregulated in human HCC tissues. Yet miRNA-101, an anti-DNA-PKcs miRNA, was downregulated. Over-expression of miR-101 in HepG2 cells inhibited DNA-PKcs expression and cell proliferation. Together, these results indicate that KU-0060648 inhibits HCC cells through DNA-PKcs-dependent and -independent mechanisms.

BackgroundRisk factors for venous thromboembolism (VTE) of total joint arthroplasty (TJA) have been examined by many studies. A comprehensive systematic review of recent findings of high evidence level in this topic is needed.MethodsWe conducted a PubMed search for papers published between 2003 and 2013 that provided level-I and level-II evidences on risk factors for VTE of TJA. For each potential factors examined in at least three papers, we summarize the the number of the papers and confirmed the direction of statistically significant associations, e.g. “risk factor” “protective factor” or “controversial factor”.ResultsFifty-four papers were included in the systematic review. Risk factors found to be associated with VTE of both total hip arthroplasty and total knee arthroplasty included older age, female sex, higher BMI, bilateral surgery, surgery time > 2 hours. VTE history was found as a VTE risk factor of THA but an controversial factor of TKA. Cemented fixation as compared to cementless fixation was found as a risk factor for VTE only of TKA. TKA surgery itself was confirmed as a VTE risk factor compared with THA surgery.ConclusionsThis systematic review of high level evidences published in recent ten years identified a range of potential factors associated with VTE risk of total joint arthroplasty. These results can provide informations in this topic for doctors, patients and researchers.

Tranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.