Citations

AbstractRecent population studies suggest an intriguing inverse relationship between several types of cancer and neurodegenerative diseases, including Alzheimer's disease. Understanding the intersection of the underlying biology for these two distinct families of diseases with one another may offer novel approaches to identify new therapeutic approaches and possible opportunities to repurpose existing drug candidates. The Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened a one‐day workshop to delve into this discussion. Workshop participants outlined research focus areas, potential collaborations, and partnerships for future action.

AbstractIntroductionAfrican Americans' (AAs) late‐onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.MethodsWe conducted a genome‐wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome‐wide set of single‐nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.ResultsTwo SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome‐wide significant evidence of association with the posterior liability.DiscussionAn informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

Objective: Vascularized toe joint transfer for finger proximal interphalangeal joint (PIPJ) reconstruction is a well-described technique in the literature. However, the reconstructed PIPJ is known to have issues with suboptimal range of motion and extension lag. One of the reasons for this problem is the length of the intercalated bony segment. There is a lack of evidence and consensus regarding the optimal length of the intercalated segment. This study hence was performed to determine the impact of the intercalated segment length on the subsequent passive arc of motion (AOM) and extension lag of the reconstructed PIPJ. Materials and Methods: We harvested the intercalated joint graft (the toe PIPJ along with its associated extensor tendons) from the lesser toes and transferred it to the finger of cadavers. A predetermined constant PIPJ defect size of 2 cm was created on the finger. By insetting 3 different lengths of the intercalated segment to the finger PIPJ, we investigated the effect of shortened (1.5 cm), exact (2.0 cm), or lengthened (2.5 cm) intercalated segment lengths on the AOM and extension lag of the reconstructed PIPJ. Results: The average AOM of finger PIPJ was 81.0° ± 19.1° and that of the toe PIPJ was 53.6° ± 16.1°. In the group with longer intercalated segment, the average AOM was 29.9° ± 10.5° with an extension lag of 32° ± 11.7°. In the group with equal intercalated segment length, the average AOM was 49.1° ± 11.5° with an extension lag of 15.4° ± 10.6°. In the group with shorter intercalated segment, the average AOM was 70.9° ± 12.6° with an extension lag of 8.4° ± 8.9°. Conclusions: From our study, shortening the intercalated segment may provide the most reduction in the extension lag of the reconstructed PIPJ. Future studies could involve further refinement of the amount of length to be shortened. This would probably lie between 0 to 5 mm.

ObjectivesWe sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling.Materials and MethodsAdult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.ResultsAt 16 weeks post-operatively, histological scores amongst treatment groups were not statistically different (TMPG: overall 12.7, cartilage 8.6, bone 4.1; TM: overall 14.2, cartilage 9.5, bone 4.9; ED: overall 13.6, cartilage 9.1, bone 4.5). Metal scaffolds were incorporated into the surrounding bone, both in TM and TMPG. The sGAG yield was lower in the neo-cartilage regions compared with the articular cartilage (AC) controls (TMPG 20.8/AC 39.5, TM 25.6/AC 33.3, ED 32.2/AC 40.2 µg sGAG/1 mg respectively), with statistical significance being achieved for the TMPG group (p < 0.05). Hypercellularity of the neo-cartilage was found in TM and ED, as the dsDNA content was significantly higher (p < 0.05) compared with contralateral AC controls (TM 126.7/AC 71.1, ED 99.3/AC 62.8 ng dsDNA/1 mg). The highest type II collagen content was found in neo-cartilage after TM compared with TMPG and ED (TM 60%/TMPG 40%/ED 39%). Inter-treatment differences were not significant.ConclusionsTM is a highly suitable material for the reconstitution of osseous defects. TM enables excellent bony ingrowth and fast integration. However, combined with autologous periosteum, such a biocomposite failed to promote satisfactory neo-cartilage formation. Cite this article: E. H. Mrosek, H-W. Chung, J. S. Fitzsimmons, S. W. O’Driscoll, G. G. Reinholz, J. C. Schagemann. Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. Bone Joint J 2016;5:403–411. DOI: 10.1302/2046-3758.59.BJR-2016-0070.R1.