Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells.

Primary drug resistance and minimal residual disease are major challenges in the treatment of B cell neoplasms. Therefore, this study aimed to identify a novel treatment capable of eradicating malignant B cells and drug-resistant disease. Oncolytic viruses eradicate malignant cells by direct oncolysis and activation of anti-tumor immunity, have proven anti-cancer efficacy, and are safe and well tolerated in clinical use. Here, we demonstrate that the oncolytic virus coxsackievirus A21 can kill a range of B cell neoplasms, irrespective of an anti-viral interferon response. Moreover, CVA21 retained its capacity to kill drug-resistant B cell neoplasms, where drug resistance was induced by co-culture with tumor microenvironment support. In some cases, CVA21 efficacy was actually enhanced, in accordance with increased expression of the viral entry receptor ICAM-1. Importantly, the data confirmed preferential killing of malignant B cells and CVA21 dependence on oncogenic B cell signaling pathways. Significantly, CVA21 also activated natural killer (NK) cells to kill neoplastic B cells and drug-resistant B cells remained susceptible to NK cell-mediated lysis. Overall, these data reveal a dual mode of action of CVA21 against drug-resistant B cells and support the development of CVA21 for the treatment of B cell neoplasms.

Combined All-Inside Anterior Cruciate Ligament Reconstruction and Minimally Invasive Posterolateral Corner Reconstruction Using Ipsilateral Semitendinosus and Gracilis Autograft.

The anterior cruciate ligament (ACL) is the most commonly injured knee ligament, particularly among adolescents and young adults. Unrecognized posterolateral laxity is understood as a major cause of ACL reconstruction failure, and concomitant injury to the posterolateral corner (PLC) is prevalent and underdetected. We advocate screening all ACL-deficient knees for PLC injury and present a technique combining minimally invasive PLC reconstruction with anatomic all-inside ACL reconstruction. The combined procedure uses only the ipsilateral hamstring tendons representing a major surgical advantage over traditional management approaches. The semitendinosus is quadrupled and attached to 2 adjustable suspensory cortical fixation devices to form the ACL graft. The gracilis tendon is looped through the fibula head and secured in a single femoral tunnel for the PLC reconstruction via 2 minimally invasive incisions. The use of a single femoral PLC tunnel combined with a single femoral ACL socket minimizes the risk of tunnel convergence.

Prominent metalware from pelvic surgery causing dyspareunia.

We present a case of female dyspareunia secondary to metalware placement during extensive pelvic surgery following a motor vehicle accident. The patient initially had an uneventful recovery from her operations. However, she noticed pain with vaginal intercourse, due to a screw tip which was palpable on vaginal examination. X-ray imaging confirmed long screws in the medial part of an anterior column plate, which were impacting on the anterior vaginal wall. Subsequent percutaneous removal of two screws resulted in resolution of her symptoms of painful vaginal intercourse. While the pain from mechanical irritation of the vagina was resolved, the patient continues to have difficulty with intercourse, which is related to hip pain as a result of her initial injury and complex pelvic surgery.

Using simulation to train orthopaedic trainees in non-technical skills: A pilot study.

AIM: To enhance non-technical skills and to analyse participant's experience of a course tailored for orthopaedic surgeons. METHODS: A Delphi technique was used to develop a course in human factors specific to orthopaedic residents. Twenty-six residents (six per course) participated in total with seven course facilitators all trained in Crisis Resource Management providing structured feedback. Six scenarios recreated challenging real-life situations using high-fidelity mannequins and simulated patients. Environments included a simulated operating suite, clinic room and ward setting. All were undertaken in a purpose built simulation suite utilising actors, mock operating rooms, mock clinical rooms and a high fidelity adult patient simulator organised through a simulation control room. Participants completed a 5-point Likert scale questionnaire (strongly disagree to strongly agree) before and after the course. This assessed their understanding of non-technical skills, scenario validity, relevance to orthopaedic training and predicted impact of the course on future practice. A course evaluation questionnaire was also completed to assess participants' feedback on the value and quality of the course itself. RESULTS: Twenty-six orthopaedic residents participated (24 male, 2 female; post-graduation 5-10 years), mean year of residency program 2.6 out of 6 years required in the United Kingdom. Pre-course questionnaires showed that while the majority of candidates recognised the importance of non-technical (NT) skills in orthopaedic training they demonstrated poor understanding of non-technical skills and their role. This improved significantly after the course (Likert score 3.0-4.2) and the perceived importance of these skills was reported as good or very good in 100%. The course was reported as enjoyable and provided an unthreatening learning environment with the candidates placing particular value on the learning opportunity provided by reflecting on their performance. All agreed that the course achieved its intended aims with realistic simulation scenarios. Participants believed patient care, patient safety and team working would all improve with further human factors training (4.4-4.6). and felt that NT skills learnt through simulation-based training should become an integral component of their training program. CONCLUSION: Participants demonstrated improved understanding of non-technical performance, recognised its relevance to patient safety and expressed a desire for its integration in training.

Vertebral compression fractures--new clinical signs to aid diagnosis.

INTRODUCTION: Acute osteoporotic vertebral compression fractures are common and usually managed conservatively. However, a significant number will remain symptomatic, causing significant pain with considerable associated morbidity and mortality. These fractures can be effectively treated with cement augmentation. However, it is impossible to distinguish between an acute and a chronic healed fracture on plain radiographs. The definitive investigation is a magnetic resonance scan. The aim of this paper is to describe and evaluate two new clinical signs to help in the diagnosis of symptomatic fractures. A prospective study of 83 patients with suspected acute osteoporotic vertebral compression fractures was carried out. All patients had a full clinical assessment, which included closed-fist percussion of their spine and asking the patient to lie supine on the examination couch. All patients had a MRI scan. RESULTS: The closed-fist percussion sign had a sensitivity of 87.5% and a specificity of 90%. The supine sign had a sensitivity of 81.25% and a specificity of 93.33%. CONCLUSIONS: These tests will enable the practitioner to predict more accurately which patients have an acute fracture, guiding referral for further imaging.

The management of spinal metastases from renal cell carcinoma.

INTRODUCTION: Osseous metastases occur in 50% of patients with renal cell carcinoma; of these, 15% occur in the spine. The treatment options for spinal metastases secondary to renal cell carcinoma are limited. This paper considers the current management options available for spinal metastases secondary to renal cell carcinoma. PATIENTS AND METHODS: A review of four patients with spinal metastases secondary to renal cell carcinoma. RESULTS: The presentation of four cases highlighting the current management options for spinal metastases secondary to renal cell carcinoma. CONCLUSIONS: Historically, spinal metastases from renal cell carcinoma have been poorly managed; however, as the treatment of the primary disease improves, better treatment of the secondary disease is needed. Cement augmentation, used alone for prophylactic stabilisation or in conjunction with a posterior decompression and fixation, provides a useful addition in the management of these patients optimising their chance to remain ambulant, continent, and pain-free.