CXCL12-targeted immunomodulatory gene therapy reduces radiation-induced fibrosis in healthy tissues.

Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 is an immune-stromal signal implicated in fibrosis and innate response. We hypothesised that modulation of CXCL12 would phenotypically mitigate RIF.

Investigating the role connective tissue fibroblasts play in the altered muscle anatomy associated with the limb abnormality, Radial Dysplasia.

Radial dysplasia (RD) is a congenital upper limb birth defect that presents with changes to the upper limb anatomy, including a shortened or absent radius, bowed ulna, thumb malformations, a radially deviated hand and a range of muscle and tendon malformations, including absent or abnormally shaped muscle bundles. Current treatments to address wrist instability caused by a shortened or absent radius frequently require an initial soft tissue distraction intervention followed by a wrist stabilisation procedure. Following these surgical interventions, however, recurrence of the wrist deviation remains a common, long-term problem following treatment.

PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma.

Purpose: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel treatment combinations that may augment responses. and , we investigated the potential for an oncolytic vaccinia virus (GLV-1h68) delivered using isolated limb perfusion (ILP) to promote antitumor immune responses and augment response to PD-1 blockade in sarcoma.

ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment.

Purpose: ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironment. We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT).

Combined ATR and DNA-PK Inhibition Radiosensitizes Tumor Cells Independently of Their p53 Status.

Head and neck squamous cell carcinoma (HNSCC) is a significant cause of cancer deaths. Cisplatin-based chemoradiotherapy is a standard of care for locally advanced disease. ATR and DNA-PK inhibition (DNA-PKi) are actively being investigated in clinical trials with preclinical data supporting clinical translation as radiosensitizers.

Genetically modified lentiviruses that preserve microvascular function protect against late radiation damage in normal tissues.

Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy (RT) are characterized by vascular dysfunction and fibrosis causing volume loss and tissue contracture, for example, in the free flaps used for immediate breast reconstruction after mastectomy. We evaluated the efficacy of lentivirally delivered superoxide dismutase 2 (SOD2) overexpression and connective tissue growth factor (CTGF) knockdown by short hairpin RNA in reducing the severity of LAEs in an animal model of free flap LAEs.

The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence.

Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes.

Donor site morbidity of the medial plantar artery flap studied with gait and pressure analysis.

Background: The medial plantar artery flap (MPA) allows transfer of both glabrous (smooth and free from hair) and sensate tissue. It has been suggested that the non-weight bearing instep area of the foot provides tissue for transfer with minimal donor morbidity. However the abductor hallucis muscle and plantar fascia are dissected during flap harvest which may affect foot mechanics.

Keeping New Delhi metallo-β-lactamase-1 at the door.

New Delhi metallo-β-lactamase-1 is a recently described gene that codes for carbapenem resistance. Inherently transferable between Gram-negative bacteria on a plasmid that also confers extended antibiotic resistance, it represents a potentially serious problem for susceptible patients, such as burn victims, and is spreading globally at a rapid rate. The authors present a case of a septic burn patient returning from India, whose microbiological cultures grew bacteria expressing New Delhi metallo-β-lactamase-1.

Ulnar nerve compression in Guyon's canal: MRI does not always have the answer.

Lipoma is a rare cause of ulnar nerve compression in Guyon's canal. All four previously reported cases from 2000 to 2009 have been accurately diagnosed on MRI. We present a case report where the MRI and surgical findings differed and a summary of the previous cases in the literature.

Surgery for a tree surgeon? Acute presentation of contact dermatitis due to Ailanthus altissima.

A tree surgeon presented to hospital with multiple blackening, non-blanching regions of skin on both forearms, following exposure to sap from the 'tree of heaven' (Ailanthus altissima). A referral to plastic surgery was made to consider debridement. Following input from the national poisons centre and dermatology, conservative management with emollient was undertaken.

Fasciocutaneous flaps of the subscapular artery axis to reconstruct large extremity defects.

Introduction: The scapular, parascapular and thoracodorsal artery perforator (TDAP) flaps represent fasciocutaneous flaps derived from the subscapular artery axis. These flaps can be harvested individually or combined as conjoint flaps, tailored to reconstruct a wide variety of defects in the extremities. ANALYSIS AND METHODS: All patients undergoing free-flap reconstruction at North Bristol trust with a fasciocutaneous flap of the subscapular axis from April 2006 until April 2010 were included.