The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues. This includes but is not limited to embryonic, hematopoietic, mesenchymal, gut, neural, and epidermal stem cells. Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties. Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders. Not surprisingly, aberrant Wnt signaling is also associated with a wide variety of diseases, including cancer. Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation, epithelial–mesenchymal transition, and metastasis. Altogether, advances in the understanding of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway. Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt, this review aims to summarize the current knowledge of Wnt signaling in stem cells, aberrations to the Wnt pathway associated with diseases, and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

Background: The optimal treatment of complex proximal humeral fractures in adults remains controversial. We evaluated the risk of complications and the long-term outcomes in patients with a severely displaced fracture or a fracture-dislocation of the proximal part of the humerus treated with open reduction and plate fixation (ORIF). Methods: Between 1995 and 2012, 5,897 consecutive patients with a proximal humeral fracture were referred to a specialist shoulder clinic for surgical assessment. Indications for surgery included anterior or posterior fracture-dislocation, substantial tuberosity involvement with >1 cm of displacement in a Neer 3 or 4-part fracture configuration, disengagement of the head from the shaft, or severe varus or valgus deformity of the head. All patients who met the surgical criteria and had been followed for 2 years were included, and standardized clinical and radiographic assessments of outcomes were performed. At a median of 10.8 years (range, 5 to 22 years) after ORIF, all surviving cognitively intact patients completed a patient-reported questionnaire assessing functional outcomes and satisfaction. Results: Three hundred and sixty-eight patients (6.2%) met the inclusion criteria and had the appropriate follow-up. The study population had a high rate of complex fracture configurations; 77.2% had tuberosity involvement, 54.1% had complete head-shaft disengagement, and 44.0% had a dislocated head. Eighty-seven patients (23.6%) had postoperative stiffness, 25 (6.8%) had fixation failure/nonunion, and 16 (4.3%) had late osteonecrosis/posttraumatic osteoarthritis; these complications were the reason for the majority of the reoperations in the cohort. The survivorship until any reoperation was 74% at 10 years, but when reoperations for stiffness were excluded, the survivorship was 90% during the same time period. The patients’ mean levels of pain, function, and satisfaction with treatment were good to excellent. Conclusions: Our results support the use of primary ORIF in medically fit patients with a severely displaced fracture or a fracture-dislocation of the proximal part of the humerus in centers where the expertise to carry out such treatment exists. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Proximal humerus fractures are the third most common fracture type in adults, with their incidence increasing over time. There are varied approaches to both the classification and treatment of proximal humerus fractures. Optimal treatments for this fracture type are still widely open to debate. This review summarizes the current and historical treatment modalities for proximal humerus fractures. In this paper, we provide updates on the advances and trends in the epidemiology, classification, and operative and nonoperative treatments of proximal humerus fractures.

Templating is an important aspect of preoperative planning for total hip arthroplasty and can help determine the size and positioning of the prosthesis. Historically, templating has been performed using acetate templates over printed radiographs. As a result of the increasing use of digital imaging, surgeons now either obtain additional printed radiographs solely for templating purposes or use specialized digital templating software, both of which carry additional cost. The purposes of this study was to compare acetate templating of digitally calibrated images on an LCD monitor to digital templating in terms of (1) accuracy; (2) reproducibility; and (3) time efficiency. Acetate onlay templating was performed directly over digital radiographs on an LCD monitor and was compared with digital templating. Five separate observers participated in this study templating on 52 total hip arthroplasties. For the acetate templating, the digital images were magnified to the scaled reference on the templates provided by the manufacturer (ratio 1.2:1) before templating using a 25-mm marker as a reference. Both the acetate and digital templating results were then compared with the actual implanted components to determine accuracy. Interobserver and intraobserver variability was determined by an intraclass correlation coefficient. Observers recorded time to complete templating from the time of complete upload of patients’ imaging onto the system to completion of templating. Both acetate and digital templates demonstrated moderate accuracy in predicting within one size of the eventual implanted acetabular cup (77% [199 of 260]; 70% [181 of 260], respectively; p = 0.050; 95% confidence interval [CI], 0.058–0.32), whereas acetate templating was better at predicting the femoral stem compared to digital templating (75% [195 of 260]; 60% [155 of 260], respectively; p < 0.001; 95% CI, 0.084–0.32). Acetate templating showed moderate to substantial interobserver agreement (cup intraclass correlation coefficient [ICC] = 0.55; 95% CI, 0.14–0.86; femoral ICC = 0.75; 95% CI, 0.39–0.95) and both methods showed almost perfect intraobserver agreement in reproducibility (acetate cup ICC = 0.82; 95% CI, 0.66–0.97; acetate femoral ICC = 0.86; 95% CI, 0.74–0.97; digital cup ICC = 0.82; 95% CI, 0.68–0.97; digital femoral ICC = 0.88; 95% CI, 0.77–1.0). Acetate templating could be performed more quickly (acetate mean 119 seconds; range, 37–220 seconds versus 154 seconds; range, 73–343 seconds; p < 0.001). Acetate onlay templating on digitally calibrated images can be a reliable substitute for digital templating using specialized software. It is quicker to perform and much less expensive. Hospitals and practices need not purchase expensive software, particularly at lower volume centers. Level III, diagnostic study.