Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology—and particularly clustered regularly interspaced short palindromic repeats (CRISPR)—will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.

Background: Although the medial compartment continues to sustain some loading after medial opening wedge high tibial osteotomy (MOWHTO) in varus-deformed knees, no studies have examined the relationship between medial meniscal extrusion (MME) and patient-reported outcome measures after MOWHTO. Purpose: To examine whether compartmental baseline MME was associated with patient-reported outcome measures after MOWHTO. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study was composed of 149 MOWHTOs in 147 patients with clinical and radiological assessments. Patients were grouped according to severity of MME in the medial compartment at the time of surgery. MME was categorized into 4 groups according to MOAKS (MRI [magnetic resonance imaging] Osteoarthritis Knee Score) criteria and relative value of MME. We compared preoperative characteristics, including Kellgren-Lawrence (KL) grading scale, meniscal tear pattern, and postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores. Associations between extent of MME and WOMAC subscores at postoperative 1 and 2 years were assessed with generalized linear models. Results: Pattern of meniscal tear ( P < .05) and KL grade ( P < .05) were associated with MME. Patients with KL grades 3 and 4 at the time of surgery had significantly greater MME than those with KL grade 2 ( P < .05). When patients were divided into 4 groups according to MOAKS criteria at the time of surgery, there were significant differences in WOMAC pain scores among groups at 1 and 2 years after the operation (all P < .05). The WOMAC function score also differed among groups at postoperative 1 year ( P < .05) but not postoperative 2 years ( P > .05). When patients were divided into 4 groups according to relative MME at the time surgery, the WOMAC pain score differed significantly among groups at postoperative 1 and 2 years (all P < .05). Analysis of WOMAC pain score as the dependent variable in multivariate analyses revealed that severity of absolute and relative MME and KL grade were independent predictors of worse WOMAC pain score at postoperative 1 and 2 years (all P < .05). Conclusion: Greater preoperative MME at the time of surgery was associated with inferior patient-reported outcomes, especially pain, in patients with MOWHTO at 1 and 2 years after surgery.

Central sensitization (CS) has been extensively researched as a cause of persistent pain after total knee arthroplasty (TKA). This systematic review study sought to investigate the diagnosis of CS in patients who underwent TKA for knee osteoarthritis (OA) and the effect of CS on clinical outcomes after TKA. Three comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies that evaluated the outcomes of TKA in knee OA patients with CS. Data extraction, risk of bias assessment, and (where appropriate) meta-analysis were performed. The standardized mean difference (SMD) with a 95% confidence interval was used to assess the different scales of pain. A total of eight studies were selected, including two retrospective studies and five prospective observational studies. One study used additional randomized controlled trial data. Five studies were finally included in the meta-analysis. All studies had a minimum follow-up period of 3 months. The Central Sensitization Inventory (CSI), whole-body pain diagram, and quantitative sensory testing (QST) were used for measuring CS. The pooled analysis showed that patients with CS had more severe postoperative pain after TKA (SMD, 0.65; 95% CI, 0.40–0.90; p < 0.01) with moderate heterogeneity (I2 = 60%). In patients who underwent TKA with knee OA, CSI is most often used for the diagnosis of CS, and the QST and whole-body pain diagram are also used. CS is closely associated with more severe and persistent pain after TKA.