BackgroundInhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents.MethodsIn this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function.ResultsAccordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy.ConclusionsWe identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.

Introduction Pipkin fractures are rare events and usually occur as a consequence for high-energy trauma. Surgery to obtain anatomical reduction and fixation is the mainstay treatment for the majority of these injuries; nonetheless, controversy exists regarding the best surgical approach. Description of the Case We present the case of a 41-year-old male, which sustained a type II Pipkin fracture following a motorcycle accident. In the emergency department, an emergent closed reduction was performed, followed by surgery five days later. Using a surgical hip dislocation, a successful anatomical reduction and fixation was performed. After three years of follow-up, the patient presented with a normal range of motion, absent signs for avascular necrosis or posttraumatic arthritis, but with a grade II heterotopic ossification. Discussion Safe surgical hip dislocation allows full access to the femoral head and acetabulum, without increasing the risk for a femoral head avascular necrosis or posttraumatic arthritis. Simultaneously, this surgical approach gives the opportunity to repair associated acetabular or labral lesions, which explains the growing popularity with this technique. Conclusion Although technically demanding, safe surgical hip dislocation represents an excellent option in the reduction and fixation for Pipkin fractures.

Diffuse-type tenosynovial giant-cell tumours of the knee (D-TGCT) have a very high complication rate. The recurrence rate for D-TGCT is mainly dependent on an initially successful resection of the lesion. The standard of care for this disease involves early surgery with synovectomy. Available surgical techniques may include an arthroscopic or open surgery; however, there is a lack of consensus on which technique should be used, and when. Arthroscopic excision is effective in minimizing morbidity and surgery-related complications, while an open surgical technique provides a more successful resection with a lower incidence of local recurrence. We could not conclude with confidence which of the surgical techniques is better at stopping a progression towards osteoarthritis and the need for a total knee arthroplasty. Cite this article: EFORT Open Rev 2020;5:339-346. DOI: 10.1302/2058-5241.5.200005

Aneurysmal bone cysts (ABCs) are benign, expansible, nonneoplastic lesions of the bone, characterized by channels of blood and spaces separated by fibrous septa, which occur in young patients and, occasionally, with aggressive behavior. Giant ABC is an uncommon pathological lesion and can be challenging because of the destructive effect of the cyst on the bones and the pressure on the nearby structures, especially on weight-bearing bones. In this scenario, en bloc resection is the mainstay treatment and often demands complex reconstructions. This paper reports a difficult case of an unusual giant aneurysmal bone cyst, which required extensive resection and a knee fusion like reconstruction with tibia allograft.

Objectives. Evaluate the impact of a Quality and Safety Program (QSP) on the reduction of blood loss and transfusion needs in pediatric spinal deformity surgery, while defining risk factors for transfusion. Background. Multimodal plan aiming to minimize transfusion needs has been shown to reduce transfusions and index rates in spinal deformity surgery. Anticipating blood loss and transfusion may help direct resources to patient needs or encourage reconsideration of the surgical plan. Methods. This is a single-center retrospective study of prospectively collected data. Impact of this multimodal plan was studied on idiopathic deformities (Group A, 109 patients) and scoliosis associated with syndromic, neuromuscular, and muscular dystrophies (Group B, 100 patients), both before and after QSP. Results. A decrease in total estimated blood loss was observed. In Group A, transfused patients decreased from 83.7% to 28% (p<0.001, odds: 0.077), and, in Group B, from 98.7% to 66% (p<0.01, odds: 0.038). Pearson’s correlation identified patient body weight (r = 0.245, p=0.001) and Cobb angle (r = 0.175, p=0.017) as factors related to blood loss. A linear regression model to estimate hematic losses revealed that only body weight and transfusion showed predictive power, resulting in a low predictive model (R2 = 0.156; F(3,167) = 15.483, p<0.001). A mediated model to explain blood loss was built based on a set of variables influencing transfusion which is, in turn, related to blood loss. Conclusion. Transfusion needs in scoliosis surgery can be substantially reduced following a multimodal approach. The success of a program is strongly dependent on team effort, and the introduction of a risk assessment tool for transfusion needs indirectly assesses surgical risk, thus allowing relocation of resources to decrease blood loss.