Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls.

Constrained or unconstrained shoulder replacement for musculoskeletal tumor resections?

Background: Many options exist for reconstructing the shoulder after large bony resections of the proximal humerus. One of the more widely used is endoprosthetic replacement. Proximal migration of unconstrained hemiarthroplasty articulations may cause difficulties particularly in the setting of loss of the rotator cuff and/or deltoid musculature.

Is an Acetabular Cage and Cement Fixation Sufficiently Durable for the Treatment of Destructive Acetabular Metastases?

Background: Destructive bony acetabular metastases cause pain, pathological fractures, and loss of mobility. Although multiple fixation options are available, we have favored a rigid stainless steel partial pelvic cage for acetabular fixation in these patients; however, little is known about the durability of this approach. QUESTION/PURPOSES: (1) How common was loss of fixation in a small series of metastatic acetabular defects treated with an acetabular cage and cemented total hip replacement? (2) What is the implant survival free from reoperation or revision at 2 and 4 years using a competing-risks survivorship estimator in patients thus treated? (3) What complications were associated with the treatment? (4) What level of postoperative mobility was achieved?

Methods: Between 2006 and 2017, we treated all acetabular metastases that needed surgical intervention, not amenable to conventional cemented THA alone with our single technique of acetabular partial pelvic cage and cemented total hip replacement.

Implementing Lean in Academic Primary Care.

Background: Lean is emerging as a quality improvement (QI) strategy in health care, but there has been minimal adoption in primary care teaching practices. This study describes a strategy for implementing Lean in an academic family medicine center and provides a formative assessment of this approach.

Methods: A case study of the University of North Carolina Family Medicine Center that used the Consolidated Framework for Implementation Research to guide a formative evaluation.

Extremophiles in an Antarctic Marine Ecosystem.

Recent attempts to explore marine microbial diversity and the global marine microbiome have indicated a large proportion of previously unknown diversity. However, sequencing alone does not tell the whole story, as it relies heavily upon information that is already contained within sequence databases. In addition, microorganisms have been shown to present small-to-large scale biogeographical patterns worldwide, potentially making regional combinations of selection pressures unique.

An in vitro human skin test for assessing sensitization potential.

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals.

Single institution retrospective review of perioperative chemotherapy in adult and adolescent patients with operable osteosarcoma.

Aims: Perioperative chemotherapy has improved the prognosis for patients with operable osteosarcoma. The literature is conflicting about which regimen is optimal. The aim of this study was to evaluate the survival outcomes of two cohorts of patients with operable osteosarcoma treated with different perioperative chemotherapy regimens.

Evaluation of the pressure leak test in increasing the lifespan of flexible ureteroscopes.

Introduction: Flexible ureteroscopes are expensive and delicate instruments that are integral in the offering of a minimally invasive technique of diagnosis and treatment of urolithiasis. Published literature has identified the importance of early damage recognition in preventing frequent use of the scope that would lead to further damage and high repair and replacement costs. Our study was designed to examine the outcome of the pressure leak test on the condition of flexible ureteroscopes after every use and analysing the damage and costs of maintenance.

Bone Regeneration Based on Tissue Engineering Conceptions - A 21st Century Perspective.

The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity.

The story of the condom.

Condoms have been a subject of curiosity throughout history. The idea of safer sex has been explored in ancient and modern history, and has been used to prevent venereal diseases. We conducted a historical and medical review of condoms using primary and secondary sources as well as using the RSM library and the internet.

Proteus: Mythology to modern times.

Aims: It is common knowledge that proteus bacteria are associated with urinary tract infections and urinary stones. Far more interesting however, is the derivation of the word proteus. This study examines the origin of the word proteus, its mythological, historical and literary connections and evolution to present-day usage.

Fournier's gangrene associated with intradermal injection of cocaine.

Introduction: Cocaine abuse is associated with a number of medical complications, most notably arrhythmias, myocardial infarction, and cerebral hemorrhages. The injection of cocaine in the penis has been predominantly recorded into the corpus cavernosae and is associated with priapism.

Aim: Here we describe the injection of subcutaneous cocaine within the penile shaft skin producing ischemic necrosis and Fournier's gangrene.

[Bone tissue engineering. Reconstruction of critical sized segmental bone defects in the ovine tibia].

Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds.Critical sized ovine tibial defects were created and stabilized.

Treatment of long bone defects and non-unions: from research to clinical practice.

The treatment of long bone defects and non-unions is still a major clinical and socio-economical problem. In addition to the non-operative therapeutic options, such as the application of various forms of electricity, extracorporeal shock wave therapy and ultrasound therapy, which are still in clinical use, several operative treatment methods are available. No consensus guidelines are available and the treatments of such defects differ greatly.

Functional outcome of arthrodesis with a vascularized fibular graft and a rotational latissimus dorsi flap after proximal humerus sarcoma resection.

Background: The prognosis of humeral sarcomas has improved greatly in the past 20 years. As a result, the challenges for orthopedic oncologists include long-term handicap and local morbidity.

Methods: Shoulder reconstruction after the resection of sarcomas with the proximal humerus was evaluated for 55 patients from 1990 to 2007 at two universities.

Comprehensive mapping of p53 pathway alterations reveals an apparent role for both SNP309 and MDM2 amplification in sarcomagenesis.

Purpose: Reactivation of p53 tumor suppressor activity in diseases such as soft-tissue sarcoma is considered an attractive means of targeted therapy. By systematically assessing alterations affecting the p53 pathway, we aimed to (a) classify sarcoma subtypes, (b) define a potential role in malignancy, and (c) identify potential patient biomarkers in this heterogeneous disease.

Experimental Design: We have mapped mutational events in a panel of 192 benign or malignant bone and soft-tissue sarcomas.

Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases.

We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P < 0.

Effect of hospital and surgeon volume on patient outcomes following treatment of abdominal aortic aneurysms: a systematic review.

Objectives: This systematic review assessed the efficacy of centralisation for the treatment of unruptured and ruptured abdominal aortic aneurysms. Patient outcomes achieved by low and high volume hospitals/surgeons, including morbidity, mortality and length of hospital stay, were used as proxy measures of efficacy.

Design: Systematic review was designed to identify, assess and report on peer-reviewed articles reporting outcomes from unruptured and ruptured abdominal aortic aneurysms.

Centralization and the relationship between volume and outcome in knee arthroplasty procedures.

Background: Centralization aims to reduce adverse patient outcomes by concentrating complex surgical procedures in specified hospitals.

Objectives: This review assessed the efficacy of centralization for knee arthroplasty by examining the relationship between hospital and surgeon volume and patient outcomes.

Data Sources And Review Methods: The systematic review identified studies using multiple databases, including Medline and Embase.

Radical prostatectomy: a systematic review of the impact of hospital and surgeon volume on patient outcome.

Background: To assess the impact of hospital and surgeon volume on mortality, morbidity, length of hospital stay and costs of radical prostatectomy (RP).

Methods: This systematic review identified relevant studies published between 1997 and June 2007. Inclusion of papers was established through application of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision.

Systematic review of the impact of volume of oesophagectomy on patient outcome.

Purpose: This systematic review aims to assess whether overall survival, mortality, morbidity, length of stay and cost of performing oesophagectomy are related to surgical volume.

Methods: A systematic search strategy from 1997 until December 2006 was used to retrieve relevant studies. Inclusion of articles was established through application of a predetermined protocol, independent assessment by two reviewers and a final consensus decision.

Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone.

Background: Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Patients who respond poorly to chemotherapy have a higher risk of metastatic disease and 5-year survival rates of only 10-20%. Therefore, identifying molecular targets that are specific for OS, or more specifically, metastatic OS, will be critical to the development of new treatment strategies to improve patient outcomes.

Limb salvage for soft-tissue sarcomas of the foot and ankle.

We evaluated the oncological and functional outcome of 27 patients who had limb salvage for a soft-tissue sarcoma of the foot or ankle between 1992 and 2007, with a mean follow-up of 7.5 years (1.05 to 16.