Multidrug Transporters and Alterations in Sterol Biosynthesis Contribute to Azole Antifungal Resistance in Candida parapsilosis.

While much is known concerning azole resistance in Candida albicans, considerably less is understood about Candida parapsilosis, an emerging species of Candida with clinical relevance. We conducted a comprehensive analysis of azole resistance in a collection of resistant C. parapsilosis clinical isolates in order to determine which genes might play a role in this process within this species. We examined the relative expression of the putative drug transporter genes CDR1 and MDR1 and that of ERG11. In isolates overexpressing these genes, we sequenced the genes encoding their presumed transcriptional regulators, TAC1, MRR1, and UPC2, respectively. We also sequenced the sterol biosynthesis genes ERG3 and ERG11 in these isolates to find mutations that might contribute to this phenotype in this Candida species. Our findings demonstrate that the putative drug transporters Cdr1 and Mdr1 contribute directly to azole resistance and suggest that their overexpression is due to activating mutations in the genes encoding their transcriptional regulators. We also observed that the Y132F substitution in ERG11 is the only substitution occurring exclusively among azole-resistant isolates, and we correlated this with specific changes in sterol biosynthesis. Finally, sterol analysis of these isolates suggests that other changes in sterol biosynthesis may contribute to azole resistance in C. parapsilosis.

Multidisciplinary clinic care improves adherence to best practice in head and neck cancer.

PURPOSE: Multidisciplinary team (MDT) care is widely accepted as best practice for patients with head and neck cancer, although there is little evidence that MDT care improves head and neck cancer related outcomes. This study aims to determine the impact of MDT care on measurable clinical quality indicators (CQIs) associated with improved patient outcomes. MATERIALS AND METHODS: Patients treated for head and neck cancer at Ipswich Hospital from 2001 to 2008 were identified. Comparisons were made in adherence to CQIs between patients treated before (pre MDT) and after (post MDT) the introduction of the MDT. Associations were tested using the Chi-square and Whitney U-test. RESULTS: Treatment post MDT was associated with greater adherence to CQIs than pre MDT. Post MDT had higher rates of: dental assessment (59% versus 22%, p<.0001), nutritional assessment (57% versus 39%, p=.015), PET staging (41% versus 2%, p<.0001), chemo-radiotherapy (CRT) for locally advanced disease (66% versus 16%, p<.0001) and use of adjuvant CRT for high risk disease (49% versus 16%, p<.0001). The interval between surgery and radiotherapy was shorter in the post MDT group (p=.009) as was the mean length of hospitalization (p=.002). CONCLUSIONS: This study highlights the measurable advantages of MDT care over the standard, less formalized, referral process.

Successful management of an aortoesophageal fistula caused by a fish bone--case report and review of literature.

We report a case of aortoesophageal fistula (AEF) caused by a fish bone that had a successful outcome. Aortoesophageal fistula is a rare complication of foreign body ingestion from which few patients survive. Over one hundred cases of AEF secondary to foreign body ingestion have been documented but only seven, including our case, have survived over 12 months. Treatment involved stabilising the patient with a Sengstaken-Blakemore tube and insertion of a thoracic aortic endovascular stent-graft. Unfortunately the stent became infected and definitive open surgical repair involved removing the stent, replacing the aorta with a homograft and coverage with a left trapezius flap while under deep hypothermic arrest.