es, with the final aim of detecting early and subtle alterations of gait.A series of novel N-benzylbenzamide derivatives were designed and synthesized as tubulin polymerization inhibitors. Among fifty-one target compounds, compound 20b exhibited significant antiproliferative activities with IC50 values ranging from 12 to 27 nM against several cancer cell lines, and possessed good plasma stability and satisfactory physicochemical properties. Mechanism studies demonstrated that 20b bound to the colchicine binding site and displayed potent anti-vascular activity. Notably, the corresponding disodium phosphate 20b-P exhibited an excellent safety profile with the LD50 value of 599.7 mg/kg (i.v. injection), meanwhile, it significantly inhibited tumor growth and decreased microvessel density in liver cancer cell H22 allograft mouse model without obvious toxicity. Collectively, 20b and 20b-P are novel promising anti-tubulin agents with more druggable properties and deserve to be further investigated for cancer therapy.The purple pigmentation in the epidermis of swollen roots of 'Tsuda’ turnip (Brassica rapa subsp. rapa) is induced by light, providing a good system to investigate the genetic mechanism of light-dependent anthocyanin biosynthesis in B. rapa. Here, we identified the R2R3 MYB transcription factor gene PRODUCTION OF ANTHOCYANIN PIGMENT1 (BrPAP1a) as the critical gene in the anthocyanin-defective mutant w68. A nucleotide mutation in the turn region of the R3 domain was screened, which caused an amino acid substitution from glycine to serine (G94S). Functional analysis showed that the interaction of BrPAP1a with two bHLH factors ENHANCER OF GLABRA 3 (BrEGL3) and TRANSPARENT TESTA 8 (BrTT8) were impaired by the mutation. Expression of BrTT8 was activated by BrPAP1a and enhanced by MYB-bHLH-WDR (MBW) complexes, but blocked by the mutation. Furthermore, BrPAP1a directly bound the MYB-recognizing element (MRE) in the BrTT8 promoter, while the G94S substitution caused a loss of DNA-binding activity. Our findings indicate that G94 is required for protein interaction with BrTT8 and BrEGL3 and DNA-binding of BrPAP1a to activate BrTT8 expression, which leads to anthocyanin biosynthesis. Collectively, our data indicate the importance of the highly conserved amino acids within R2R3 MYB proteins in regulating anthocyanin biosynthesis and could aid programs to increase anthocyanins in turnip roots.

Intraoperative systemic lidocaine has become widely accepted as an adjunct to general anesthesia, associated with opioid-sparing and enhanced recovery. We hypothesized that perioperative systemic lidocaine improves postoperative pain and enhances the quality of recovery (QoR) in patients following video-assisted thoracic surgery (VATS).

Prospective, single-center, double-blind, randomized placebo-controlled clinical trial.

Single institution, tertiary university hospital.

Adult patients aged 18 to 65 undergoing VATS were eligible for participation.

Patients enrolled in this study were randomized to receive either system lidocaine (a bolus of 1.5mgkg

, followed by an infusion of 2mgkg

h

until the end of the surgical procedure) or identical volumes and rates of 0.9% saline.

The primary outcome was a global QoR-15 score 24h after surgery. Secondary outcomes included postoperative pain score, cumulative opioid consumption, emergence time, length of PACU stay, adverse events, and patient satisfaction.

There was no difference in the global QoR-15 scores at 24h postoperatively between the lidocaine and saline groups (median 117, IQR 113.5-124, vs. median 116, IQR 111-120, P=0.067), with a median difference of 3 (95% CI 0 to 6, P=0.507). Similarly, postoperative pain scores, postoperative cumulative opioid consumption, PACU length of stay, the occurrence of PONV, and patient satisfaction were comparable between the two groups (all P>0.05).

Our current findings do not support using perioperative systemic lidocaine as a potential strategy to improve postoperative pain and enhance QoR in patients undergoing VATS.

Chinese Clinical Trial Registry (identifier ChiCTR1900027515).

Chinese Clinical Trial Registry (identifier ChiCTR1900027515).

The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study.

Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS).

Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS= 0.01/0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS= 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P= 0.02), PFS2 (P= 0.01), and OS (P= 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio= 0.60; P= 0.03) and mixed subtypes (hazard ratio= 0.44; P= 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study.

We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab.

We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab.

Entrectinib is a tropomyosin receptor kinase inhibitor approved for the treatment of neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours based on single-arm trials. Traditional randomised clinical trials in rare cancers are not feasible; we conducted an intrapatient analysis to evaluate the clinical benefit of entrectinib versus prior standard-of-care systemic therapies.

Patients with locally advanced/metastatic NTRK fusion-positive tumours enrolled in the global phase II, single-arm STARTRK-2 trial were grouped according to prior systemic therapy and response. The key analysis used growth modulation index [GMI; ratio of progression-free survival (PFS) on entrectinib to time to discontinuation (TTD) on the most recent prior therapy]; ratio ≥1.3 indicated clinically meaningful efficacy. Additional analyses investigated TTD and objective response rate (ORR) for entrectinib and prior therapies.

Seventy-one patients were included; 51 received prior systemic therapy. In 38 patients whos of entrectinib in a rare, heterogeneous adult population.

Periprosthetic osteolysis (PPOL) is a common complication after total knee arthroplasty (TKA) and is most commonly caused by wear-induced particles.

We report an unusual case of massive bilateral PPOL in the posterior flanges of the femur and patellae 4 years after bilateral uncemented TKA without patellar resurfacing in a 71-year old female. Bilateral staged revision surgery including polyethylene exchange and allograft morselized bone impaction was performed to treat the osteolytic lesions. There were no signs of implant malalignment, polyethylene wear or component loosening.

Several factors are associated with an increased risk on PPOL (e.g. polyethylene sterilization method, patient age, male gender). Surgical intervention in the context of massive PPOL should include replacement of a potential particle generator (most often polyethylene), correction of potential malalignment, treatment of bone defects and assessment of implant anchorage.

This report highlights the available evidence on clinical presentation, associated risk factors and preferred treatment strategy of massive osteolytic lesions after TKA according to available evidence.

This report highlights the available evidence on clinical presentation, associated risk factors and preferred treatment strategy of massive osteolytic lesions after TKA according to available evidence.Our Moroccan context is experiencing an increase in the frequency of renal tumors. This trend can be explained by the generalization of the use of imaging, in particular abdominal ultrasound, which has become almost systematic among general practitioners (Godley and Ataga, 2000 [1]). The specificity of kidney cancer is anatomopathological heterogenicity histological type, nuclear grade, tumor stage, these elements constitute the most important prognostic factors. Renal biopsy appears to be a safe and reliable solution with a low risk of tumor seeding and complications, however it cannot provide all the detailed histological information needed. Hence the interest in the abdominal scanner. The abdominal scanner is the reference examination for the evaluation of renal tumors, it diagnoses the tumor, specifies these characteristics, it assesses the loco regional, venous extension. The objective of our study is to correlate pathological and CT findings of 70 kidney cancer in order to determine the reliability of CT in kidney cancer and its extension.

Lateral premalleolar bursitis develops on the dorsolateral aspect of the foot anterior to the lateral malleolus, distinct from lateral malleolar bursitis located just around the lateral malleolus.

A 71-year-old woman visited an orthopedic clinic about 40 years after an episode of ankle sprain and was diagnosed with lateral premalleolar bursitis and osteoarthritis of the left ankle. Stress radiography revealed left ankle anterolateral malleolar bursitis with varus and anterior instability. We opted for less invasive arthroscopic ankle arthrodesis over open resection to stop the communication of the bursitis with the ankle joint. The lateral premalleolar bursitis was located just over the anterolateral portal. The remaining cartilage in the talotibial joint was removed and the subchondral surface was exposed and curetted down to a bleeding surface by ankle arthroscopy. The talotibial joint was fixed with 3 6.0-mm cannulated cancellous screws. The foot and ankle were immobilized by cast for 4 weeks. Bony union was achieved about 8 weeks postoperatively. The patient could perform daily activities without pain and with no recurrence of the lateral premalleolar bursitis at the 1.5-year follow-up.

To our knowledge, this is the first report on arthroscopic arthrodesis for ankle osteoarthritis with recalcitrant lateral premalleolar bursitis caused by the check valve mechanism of chronic ankle instability after old ankle sprain.

We report a case of arthroscopic arthrodesis for osteoarthritis of the ankle associated with lateral premalleolar bursitis caused by the check valve mechanism of chronic ankle instability after old ankle sprain.

We report a case of arthroscopic arthrodesis for osteoarthritis of the ankle associated with lateral premalleolar bursitis caused by the check valve mechanism of chronic ankle instability after old ankle sprain.