Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease.

Bosworth ankle fracture-dislocation: current concept review.

Bosworth fracture (BF) is a special type of locked ankle fracture-dislocation, characterized by displacement of a fragment of the fractured fibula from the fibular notch behind the posterior surface of the distal tibia. BF is a complex injury affecting multiple structures of the ankle joint, which is still frequently misjudged even today, potentially leading to severe complications. CT examination, including 3D reconstructions, should be the diagnostic standard in BF, as it provides a complete picture of the fracture pathoanatomy, most prominently the morphology of the frequently associated posterior malleolar fracture.

Exceptional Response of -Mutated Acinar Cell CUP to BRAF/MEK Inhibition.

Complete remission of BRAF V600E-driven ACC CUP by BRAF/MEK inhibition underscores importance of precision oncology.

NRN1 interacts with Notch to increase oncogenic STAT3 signaling in melanoma.

Background: Melanoma is a highly heterogeneous cancer, in which frequent changes in activation of signaling pathways lead to a high adaptability to ever changing tumor microenvironments. The elucidation of cancer specific signaling pathways is of great importance, as demonstrated by the inhibitor of the common BrafV600E mutation PLX4032 in melanoma treatment. We therefore investigated signaling pathways that were influenced by neurotrophin NRN1, which has been shown to be upregulated in melanoma.

Joint-Preserving Osteotomy of the Lateral Tibial Plafond for Posttraumatic Osteonecrosis: A Prospective Cohort Study.

Background: Posttraumatic osteonecrosis (ON) of the lateral distal tibia is a rare but severe complication of malleolar fractures. Treatment options include ankle fusion, arthroplasty, osteotomy, and drilling but clinical data on outcomes are limited to single case reports. The aim of this study was to prospectively evaluate the outcome following joint-preserving reconstruction.

Early history of posterior malleolus fractures in ankle fractures.

Introduction: No comprehensive treatise on the early history of fractures of posterior malleolus (PM) has yet been published, and many substantial discoveries have fallen into oblivion-particularly if not having been published in English originally.

Materials And Methods: Literature search was performed in original publications and historical sources.

Results: Early history of PM fractures from their first description up to the beginnings of their operative treatment may be divided into three basic periods, covering the era between 1828 and 1940.

BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS-mutant melanoma cells: Insights into mode of action and resistance mechanisms.

About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS-mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS-mutant melanoma, providing an ideal backbone for combination treatments.

Injury to the posterior malleolus in Maisonneuve fractures.

Purpose: The aim of this study was to describe the incidence and a complex pathoanatomy of posterior malleolus fractures in a Maisonneuve fracture.

Methods: The study included 100 prospectively collected patients with a complete clinical and radiological documentation of an ankle fracture or fracture-dislocation including a fracture of the proximal quarter of the fibula.

Results: A posterior malleolus fracture was identified in 74 patients, and in 27% of these cases it carried more than one quarter of the fibular notch.

History of proximal femur fractures in the German literature.

Introduction: German-speaking surgeons have left a deep imprint on the history of diagnostics and treatment of proximal femur fractures. Some of the studies published in German have fell into oblivion, others are cited until today, although sometimes quite inaccurately. The cause of such inaccuracies are citations from secondary sources due to unavailability of the original or inability to read it because of a language barrier.

Prevalence and Predictors of Peroneal Tendon Instability Accompanying Calcaneal Fractures.

Background: We aimed to find the prevalence of peroneal tendon instability (PTI) accompanying different types of calcaneal fractures and to determine predictors of PTI based on preoperative CT scanning.

Methods: In a retrospective cross-sectional study, preoperative CT scans of 400 consecutive calcaneal fractures undergoing surgery were reviewed for comminuted fragments in the lateral gutter of the ankle, fractures at the tip of the lateral malleolus, dislocated peroneal tendons, excessive displacement of the lateral calcaneal wall, calcaneal fracture-dislocation, superior peroneal retinaculum (SPR) avulsion fracture (fleck sign), and shape of the retromalleolar groove. The correlation of these variables with intraoperative SPR stress test, defined as the diagnostic criteria for PTI in calcaneal fractures, was evaluated.

Biomarkers in 5q-associated spinal muscular atrophy-a narrative review.

5q-associated spinal muscular atrophy (SMA) is a rare genetic disease caused by mutations in the SMN1 gene, resulting in a loss of functional SMN protein and consecutive degeneration of motor neurons in the ventral horn. The disease is clinically characterized by proximal paralysis and secondary skeletal muscle atrophy. New disease-modifying drugs driving SMN gene expression have been developed in the past decade and have revolutionized SMA treatment.

Spondylodiscitis in Geriatric Patients: What Are the Issues?

Study Design: Review article.

Objectives: A review of literature on the treatment of pyogenic spondylodiscitis in geriatric patients was performed with the aim to give an overview about these special patients and a recommendation on necessary diagnostics as well as conservative and operative treatment options.

Methods: A systematic computerized literature search was done by the spondylodiscitis working group of the German Society for Orthopedics and Trauma Surgery.

Immediate weight bearing without immobilization for operatively treated ankle fractures is safe - A systematic review.

Background: This systematic literature review compared weight bearing (WB) vs. partial- / non-weight bearing (NWB) and mobilization (MB) vs. immobilization (IMB) for surgically treated ankle fractures.

Microdialysis Reveals Anti-Inflammatory Effects of Sulfated Glycosaminoglycanes in the Early Phase of Bone Healing.

Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase.

Decoding molecular programs in melanoma brain metastases.

Melanoma brain metastases (MBM) variably respond to therapeutic interventions; thus determining patient's prognosis. However, the mechanisms that govern therapy response are poorly understood. Here, we use a multi-OMICS approach and targeted sequencing (TargetSeq) to unravel the programs that potentially control the development of progressive intracranial disease.

Ankle fractures involving the anterolateral distal tibia: medium-term clinical results of 50 cases.

Purpose: The anterolateral distal tibial rim (anterior malleolus, AM) is frequently fractured in malleolar fractures. The aim of this study was to evaluate the medium-term outcomes of malleolar fractures involving the AM.

Methods: Among 100 patients with AM fractures that were treated over a 10-year period, 50 patients were available for follow-up.

Lisfranc Arthrodesis in Posttraumatic Chronic Injuries.

Chronic injuries at the tarsometatarsal joint represent a wide array of painful malunions ranging from isolated instability to complex three-dimensional deformities with rapid development of posttraumatic arthritis. Deformity correction and arthrodesis of the symptomatic joints leads to significant pain reduction and functional improvement provided that realignment of the anatomic axes is achieved. Arthrodesis should be limited to the first to third tarsometatarsal joints, whereas interposition arthroplasty is preferred for symptomatic arthritis of the fourth to fifth tarsometatarsal joints.

Intercalary fragments in posterior malleolar fractures: incidence, treatment implications, and distribution within CT-based classification systems.

Introduction: Complex ankle fractures frequently include the posterior malleolus (PM). Despite advances in diagnostic and treatment strategies, PM fracture involvement still predisposes to worse outcomes. While not incorporated into the most common PM fracture classifications, the presence of an intercalary fragment (ICF) complicates treatment.

Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma.

BRAFV600 mutations in melanoma are targeted with mutation-specific BRAF inhibitors in combination with MEK inhibitors, which have significantly increased overall survival, but eventually lead to resistance in most cases. Additionally, targeted therapy for patients with NRASmutant melanoma is difficult. Our own studies showed that BRAF inhibitors amplify the effects of MEK inhibitors in NRASmutant melanoma.

Managing Acute Fore- and Midfoot Fractures in Patients with Diabetes.

Few is investigated about the management of acute fore- and midfoot injuries in diabetics. With well controlled diabetes, indications and techniques are similar to non-diabetics. With poorly controlled diabetes, medical optimization should be exercised.

Chopart Joint Injuries: Assessment, Treatment, and 10-Year Results.

Objectives: To investigate injury patterns and long-term outcomes of midtarsal (Chopart) injuries in a sizeable number of patients.

Design: Prospective study.

Setting: Level 1 trauma center.

Complications following surgical treatment of posterior malleolar fractures: an analysis of 300 cases.

Aims: The treatment of ankle fractures and fracture-dislocations involving the posterior malleolus (PM) has undergone considerable changes over the past decade. The aim of our study was to identify risk factors related to the occurrence of complications in surgically treated ankle fractures with PM involvement.

Patients And Methods: We retrospectively analyzed 300 patients at a mean age of 57 years with 300 ankle fractures involving the PM treated surgically at our institution over a 12-year period.

Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix.

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats.

Maisonneuve Fractures of the Ankle: A Critical Analysis Review.

»: Maisonneuve fractures (MFs), originally described as subcapital (high) fibular fractures with additional injury to the anterior and interosseous tibiofibular ligaments, display a variable injury pattern, ranging from stable to highly unstable fractures.

»: The high incidence of associated fractures of the posterior malleolus, the medial malleolus, and the anterolateral distal tibia (the "anterior malleolus") as well as the variable position of the fibula in the fibular notch (FN) warrant preoperative examination via computed tomography (CT).

»: The main goal of treatment is anatomic reduction of the distal fibula into the FN, which requires prior reduction of displaced posterior malleolar fractures, if present, to restore the integrity of the FN.