Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Caliper-verified unrestricted kinematically aligned total knee arthroplasty in Asian patients showed efficacious mid- to long-term results regardless of postoperative alignment categories.

PURPOSE: There have been insufficient data regarding the long-term results of unrestricted kinematically aligned total knee arthroplasty (unKATKA) in Asian patients. We investigated mid- to long-term clinical and radiological follow-up data of Korean patients after caliper-verified unKATKA of minimum 7.4-10 years including categorised data of postoperative tibial component, limb and knee alignment. Additionally, we analysed the preoperative distribution and postoperative restoration of coronal plane alignment of knee (CPAK) phenotypes. METHODS: This study is a retrospective analysis of 63 patients: 96 osteoarthritic underwent consecutive caliper-verified unKATKA between October 2013 and May 2016 by a single surgeon. Implant survivorship was investigated for revision for any reason. Each knee was categorised into an in-range or outlier group by three postoperative alignment parameters: tibial component, knee and limb alignment. Statistical analyses were done for any significant differences in clinical scores and implant survival rates between groups. Finally, all knees were classified into CPAK classification postoperatively and postoperatively. The CPAK restoration rate was calculated. RESULTS: Among 85 knees in the clinically confirmed group, implant survival was 98.8%. There was one case of revision due to periprosthetic fracture. The percentage postoperatively aligned in the varus (valgus) outlier range was 100% (0%) for tibial component, 16.7% (24.8%) for the knee alignment and 51% (0%) for the limb alignment. All three categories did not affect implant survival or clinical scores. Eighty one out of 96 knees (84.4%) were restored to their CPAK phenotype postoperatively. CONCLUSION: With the limitation of a case series having a small number of patients and gender deviation, our study suggests that caliper-verified unKATKA could be a good option regardless of geographical variation of constitutional alignment in patients with osteoarthritis (OA). LEVEL OF EVIDENCE: Level IV, therapeutic study.

The Morphology of a Kinematically Aligned Distal Femoral Osteotomy Is Different from That Obtained with Mechanical Alignment and Could Have Implications for the Design of Total Knee Arthroplasty.

Background: Kinematically aligned total knee arthroplasty (KA-TKA) may lead to a different pattern of osteotomy from mechanically aligned total knee arthroplasty (MA-TKA). This paper aims to analyze the effects of KA and MA on the morphology of the distal femoral osteotomy surface. Methods: Computed tomography scans of 80 TKA candidates were reconstructed into 3D models. The measurement of bone morphology was performed after the distal femur cut according to two different alignment techniques. The aspect ratio, trapezoidicity ratio, and asymmetry ratio of the distal femur were assessed. Results: The aspect ratio and the asymmetry ratio in the KA group was significantly lower than that in the MA group in the general population (p < 0.001). The trapezoidicity ratio in the KA group was significantly higher than that in the MA group in the general population (p < 0.001). Conclusions: It was found that KA-TKA and MA-TKA presented different morphologies of the distal femoral osteotomy surface, and this difference was also influenced by gender. The surgery pattern of KA-TKA and MA-TKA and gender should be considered when surgeons choose femoral prostheses.

Assessment of the Bone Mineral Density and Microstructure of the Human Femoral Head according to Different Tip-apex Distances Can Guide the Treatment of Intertrochanteric Hip Fractures.

PURPOSE: We analyzed the microstructure and bone mineral density (BMD) of the trabecular bone in the femoral head of patients with osteoporosis. MATERIALS AND METHODS: Sixteen femoral heads with osteoporotic femoral neck fractures underwent micro-computed tomography scanning. In each tip-apex distance (TAD) of 15, 20, and 25 mm, five regions of interest (ROIs) were extracted from the central, anterior, posterior, superior, and inferior sections. A total of 15 ROIs were extracted from TADs of 15, 20, and 25 mm. The measurement parameters included BMD, percent bone volume: bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), structural model index (SMI), and degree of anisotropy (DOA). RESULTS: The lowest BMD and BV/TV values were observed in the inferior region and differed significantly from those in other regions (P<0.05). Lower Tb.Th and Tb.N values were observed in the inferior region compared with those in the central region (P<0.05). The highest SMI value was observed in the inferior region (P<0.05). With TAD of 15 and 20 mm, the DOA values in the inferior region were lower than those in the anterior region (P<0.05). Lower BMD and BV/TV values were observed in the anterior, central, and inferior regions of TAD of 15 mm compared with those in the corresponding regions of TAD of 25 mm (P<0.05). CONCLUSION: Positioning the lag screw between TAD of 20 to 25 mm and in the inferior region is recommended, and TAD of less than 15 mm is not recommended.