AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer.

Purpose: To assess the safety and efficacy of AN0025 in combination with preoperative radiotherapy and chemotherapy in either short course (SCRT) or long course radiotherapy (LCRT) settings for those with locally advanced rectal cancer.

Patients And Methods: Twenty-eight subjects with locally advanced rectal cancer participated in this multicenter, open-label, Phase Ib trial. Enrolled subjects received either 250 mg or 500 mg of AN0025 once daily for 10 weeks with either LCRT or SCRT with chemotherapy (7 subjects/group).

Indications for and Risks Associated With Implant Removal After Pediatric Trauma.

A wide range of implants are used in the treatment of pediatric fractures, including wires, plates, screws, flexible rods, rigid rods, and external fixation devices. Pediatric bones differ from adult bones both mechanically and biologically, including the potential for remodeling. Implants used in pediatric trauma patients present a unique set of circumstances regarding indications, risks, timing of implant removal, weight-bearing restrictions, and long-term sequelae.

Incidence and Management of Articular Impaction in Geriatric Olecranon Fractures.

Introduction: Olecranon fractures are common in the elderly. Articular impaction is encountered occasionally, but the incidence and outcomes after treatment of this injury pattern have not been well characterized.

Methods: We evaluated a cohort of geriatric olecranon fractures to determine the incidence of articular impaction and describe a technique for open reduction and internal fixation.

Medial Column Support in Pilon Fractures Using Percutaneous Intramedullary Large Fragment Fixation.

Pilon fractures are complex injuries to the tibial plafond requiring stable fixation in the setting of effective soft tissue management, particularly in high-energy injuries, open fractures, or in geriatric individuals. Medial column support of the distal tibial metaphysis is often an essential component when applying balanced fixation. However, the biologic implications of multiple surgical approaches in the setting of damaged tissue, devitalized bone, or significant bone loss may contribute to increased complications.

Short versus long cephalomedullary nailing of intertrochanteric fractures: a meta-analysis of 3208 patients.

Objectives: The purpose of the study was to compare treatment outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures.

Data Sources: A systematic review of perioperative outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures was performed. The following databases were used: using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2019), and MEDLINE (1980-2019).

National Metrics Improved Timeliness of Antibiotic Administration for Open Extremity Fractures.

Introduction: Antibiotics have been shown to be an essential component in the treatment of open extremity fractures. The American College of Surgeons' Trauma Quality Improvement Program, based on a committee of physician leaders including orthopaedic trauma surgeons, publishes best-practice guidelines for the management of open fractures. Accordingly, it established the tracking of antibiotic timing as a metric with a plan to use that metric before trauma center site reviews.

Metaphyseal callus formation in pilon fractures is associated with loss of alignment: Is stiffer better?

Objective: To assess the relationship between metaphyseal callus formation and preservation of distal tibial alignment in pilon fractures treated with internal plate fixation.

Design: Retrospective Review SETTING: Academic Level I Trauma Center PATIENTS: Forty-two patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.

Intervention: Internal fixation with anterolateral plating, medial plating, or both.

Biomechanical Analysis of Retrograde Superior Ramus Screw Fixation Constructs.

Objective: To investigate the biomechanical performance of different size and length retrograde superior ramus screws.

Materials And Methods: A vertical superior ramus fracture was created in osteoporotic composite hemipelvis bone models (Sawbones, Vashon Island, WA). After reduction, 4 fixation groups were created by inserting either a solid 4.

How are peri-implant fractures below short versus long cephalomedullary nails different?

Background: Cephalomedullary nails are a commonly used implant for the treatment of many pertrochanteric femur fractures and are available in short and long configurations. There is no consensus on ideal nail length. Relative advantages can be ascribed to short and long intramedullary nails, yet both implant styles share the potentially devastating complication of peri-implant fracture.

How do pilon fractures heal? An analysis of dual plating and bridging callus formation.

Objectives: 1) To determine the effect of single versus dual plate metaphyseal fixation for pilon fractures on callus formation and reoperation rates, 2) to determine the effect of biomechanically matched versus unmatched fixation, and 3) to determine whether patient or surgical factors were independent predictors of bridging callus formation or need for reoperation.

Design: Retrospective comparative study.

Setting: Single level one trauma center.

New Technologies to Image Tumors.

The premise of this book is the importance of the tumor microenvironment (TME). Until recently, most research on and clinical attention to cancer biology, diagnosis, and prognosis were focused on the malignant (or premalignant) cellular compartment that could be readily appreciated using standard morphology-based imaging.

A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers.

Purpose: Gastrointestinal cancers remain areas of high unmet need despite advances in targeted and immunotherapies. Here, we demonstrate potent, tumor-selective efficacy with PF-07062119, a T-cell engaging CD3 bispecific targeting tumors expressing Guanylyl Cyclase C (GUCY2C), which is expressed widely across colorectal cancer and other gastrointestinal malignancies. In addition, to address immune evasion mechanisms, we explore combinations with immune checkpoint blockade agents and with antiangiogenesis therapy.

Comparison of the molecular and cellular phenotypes of common mouse syngeneic models with human tumors.

Background: The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. An important class of preclinical in vivo models for immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of ten commonly used mouse tumor cell lines grown in vitro culture as well as in vivo tumors.

Comparative Analysis of Mechanism-Associated 3-Dimensional Tibial Plateau Fracture Patterns.

Background: The association between tibial plateau fracture morphology and injury force mechanism has not been well described. The aim of this study was to characterize 3-dimensional fracture patterns associated with hypothesized injury force mechanisms.

Methods: Tibial plateau fractures treated in a large trauma center were retrospectively reviewed.

Posterior Sternoclavicular Dislocation: Do We Need "Cardiothoracic Backup"? Insights From a National Sample.

Objectives: To describe the incidence of and risk factors for vascular injury associated with P-SCD.

Methods: We used data from the HCUP-NIS from 2015 to 2016 and defined a cohort of patients with sternoclavicular dislocation (SCD) using ICD-10-CM diagnosis codes. We further isolated a subset with P-SCD.

Biomechanical comparison of bone-screw-fasteners versus traditional locked screws in plating female geriatric bone.

Objectives: To biomechanically compare plated constructs using nonlocking bone-screw-fasteners with interlocking threads versus locking screws with traditional buttress threads in geriatric female bone.

Methods: Eleven matched pairs of proximal and distal segments of geriatric female cadaveric tibias were used to create a diaphyseal fracture model. Nonlocking bone-screw-fasteners or locking buttress threaded screws were applied to a locking compression plate on the anterolateral aspect of the tibia placed in bridge mode.

Upregulation of PD‑L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300‑mediated NF‑κB signaling.

Programmed cell death ligand 1 (PD‑L1) expressed in cancer cells interacting with its receptor programmed cell death 1 (PD‑1) expressed in immune cells represents a regulatory axis linked to the suppression and evasion of host immune functions. The blockade of PD‑1/PD‑L1 interaction using monoclonal antibodies has emerged as an effective therapy for several solid tumors; however, durable response has been observed in a subset of patients with PD‑L1-positive tumors. Thus, the understanding of the mechanisms responsible for the expression of PD‑L1 in tumor cells may help to improve the response to PD‑L1 blockade therapies.

Reduction Techniques for Diaphyseal Femur Fractures.

Achieving and maintaining reduction in patients with a diaphyseal femur fracture may be difficult; therefore, thorough preoperative planning is required. To fully prepare for successful surgical management of diaphyseal femur fractures, surgeons must consider appropriate patient positioning and necessary tools, including surgical tables, traction devices, and instruments. Principles of acceptable reduction rely on the restoration of length, alignment, and rotation.

Two and Three-Dimensional CT Mapping of Hoffa Fractures.

Background: Hoffa fractures, coronal-plane fractures involving the distal femoral condyles, are unstable, intra-articular fractures. The aim of this study was to define the location and frequency of fracture lines and comminution zones in Hoffa fractures using computed tomography (CT) mapping in both 2-dimensional and 3-dimensional contexts.

Methods: Seventy-five Hoffa fractures (OTA/AO types 33B3.

A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice.

Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors.

Reduction Techniques for Diaphyseal Femur Fractures.

Achieving and maintaining reduction in patients with a diaphyseal femur fracture may be difficult; therefore, thorough preoperative planning is required. To fully prepare for successful surgical management of diaphyseal femur fractures, surgeons must consider appropriate patient positioning and necessary tools, including surgical tables, traction devices, and instruments. Principles of acceptable reduction rely on the restoration of length, alignment, and rotation.

Ultrasound Screening for Posterior Shoulder Dislocation in Infants with Persistent Brachial Plexus Birth Palsy.

Background: Early detection of posterior shoulder dislocation in infants with brachial plexus birth palsy (BPBP) is essential, but it may be difficult to accomplish with physical examination alone. The aim of this study was to determine the prevalence of shoulder dislocation in patients with BPBP using ultrasound and to identify which physical examination measurements correlated most with dislocation in these patients.

Methods: This study was a retrospective review of data obtained in an ultrasound screening program of infants with BPBP born from January 2011 to April 2014.

A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions.

Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs).

A Useful Preoperative Planning Technique for Transiliac-Transsacral Screws.

Stabilization of posterior pelvic ring injuries is increasingly performed using percutaneously placed iliosacral and transiliac-transsacral screws. Understanding the unique and specific anatomical variations present in each patient is paramount. Multiple methods of evaluating potential osseous fixation pathways for screw placement exist, but many require specific imaging protocols, specialized software, or modification of data.