The use of venous anastomotic flow couplers to monitor buried free DIEP flap reconstructions following nipple-sparing mastectomy.

Nipple sparing mastectomy with free tissue transfer for breast reconstruction offers excellent aesthetic outcomes but poses a challenge in monitoring the buried flap. Venous anastomotic flow couplers directly monitor buried flaps without the need for monitoring skin paddles. In a two year period we used the Synovis GEM™ flow coupler on 24 DIEP flaps. In our practice, flow couplers are effective in monitoring buried free flaps for breast reconstruction. The avoidance of a second procedure to remove a skin paddle improves patient experience and nullifies the additional flow coupler cost. One patient needed return to theatre when a Doppler wire became dislodged early in the series. There were no other issues with flap monitoring and no flap failures. We offer our tips to optimise flow coupler use.

Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.

BACKGROUND: We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. METHODS: Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence. FINDINGS: Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration. INTERPRETATION: Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.

Safety of a single aerosol administration of escalating doses of the cationic lipid GL-67/DOPE/DMPE-PEG5000 formulation to the lungs of normal volunteers.

Several groups are assessing the use of cationic lipids for respiratory gene therapy. To date no human data are available regarding the safety of intra-pulmonary cationic lipid delivery. In preparation for a trial of pulmonary delivery of the CFTR gene, we have assessed the safety of nebulised lipid GL-67/DOPE/DMPE-PEG5000 (GL-67A), the cationic lipid formulation to be used in this study. Fifteen healthy volunteers were given incremental doses of GL-67A via a Pari LC Jet nebuliser; three volunteers in each of five dosing cohorts with a week interval between cohorts. Markers of safety included clinical assessment, measurement of lung function, chest CT scan, serological testing and analysis of induced sputum. Measurements were taken before administration and at intervals up to 21 days thereafter. No adverse clinical events were seen or any statistically significant changes in spirometry or gas transfer. There were no clinically significant changes in any of the blood parameters and no CT changes were seen. Comparisons of the cellular subpopulations (neutrophils, eosinophils, lymphocytes and macrophages) in induced sputum showed no significant alterations following administration of the GL-67A. This study suggests that a single application of aerosol formulation of GL-67A does not result in clinically detectable changes when given by nebulisation into the lungs of normal volunteers and provides an indication of a lipid dose tolerated in man.

Fatal haemorrhage from mesenchymal cystic hamartoma of the lung.

A 34 year old women was admitted to the hospital with a 9 year history of intermittent haemoptysis associated with increasing breathlessness. A working diagnosis of lymphangioleiomyomatosis was made, based on clinical, radiological and histological findings. Three years later, the patient was admitted to hospital with worsening haemoptysis, which rapidly progressed and resulted in death from massive pulmonary haemorrhage. Postmortem examination and histology revealed findings consistent with multiple mesenchymal cystic hamartomas of the lungs. This is a rare condition which has previously been described as having a good prognosis. This case is the first fatality resulting directly from the disease to be reported.