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Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined.Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state.Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS. Despite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa occurs remains largely undefined. Twenty subjects undergoing functional endoscopic sinus surgery (FESS) for CRS were randomized to one of two groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal mucus, sinonasal tissues and serum at steady state. Doxycycline concentrations measured in the mucus were significantly lower compared to that in the serum (mean mucus/serum ratio = 0.16, p p p = 0.002) and the tissue (mean mucus/tissue ratio = 0.60, p Although the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complexity of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Background Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. Methods Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. Results Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. Conclusion In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.

This chapter is the first of two chapters demonstrating the wide variety of CFD studies in clinical applications presented from leading researchers in their respective fields. This chapter covers the latest research techniques and outcomes in airflow and conditioning in the nasal cavity; fluid and particle dynamics from sniffing; nasal obstruction and empty nose syndrome; nasal nitric oxide (nNO) dynamics and the ostiomeatal complex.

There is an enormous range of anatomical variants of the nasal cavity and paranasal sinuses, and these can be influenced by gender, age and ethnic adaptations to local climate. A further factor is pneumatization of the paranasal sinuses which is highly variable between individuals. When significant deviations occur from typical airway geometries, this can lead to nasal airway obstruction having the potential to significantly reduce quality of life in patients. This chapter presents the main factors affecting anatomy geometry, and common disorders, diseases, and its management.

A good understanding of the normal human nose anatomy and function is critical to perform human respiratory system computer modelling and computational fluid dynamic (CFD) analysis. This chapter provides a broad overview of the function and organisation of the human respiratory system, including essential anatomical definitions, anatomy and naming conventions, as well as particular areas of surgical interest. The topics include Functions and Organisation of the Respiratory System, and the nasal cavity anatomy, function, physiology, and histology.

BackgroundDespite the widespread prescription of antibiotics for patients with chronic rhinosinusitis (CRS), the extent to which drug distribution to the sinonasal mucosa influences their efficacy remains largely undefined.MethodsThirty subjects undergoing functional endoscopic sinus surgery (FESS) for bilateral CRS were randomized to one of three groups: 1) doxycycline (100 mg daily for seven days) 2) roxithromycin (300 mg daily for seven days) and 3) control (no antibiotics given). Drug levels were measured using liquid chromatography-tandem mass spectrometry in sinonasal secretions, sinonasal tissues and serum at steady state. Nasal endoscopy (Modified Lund-Kennedy) and Gastrointestinal Symptom Rating Scale (GSRS) scores were recorded.ResultsAntibiotic concentrations in the nasal secretions were significantly lower compared to those in the serum and tissue (mean mucus/serum ratio at steady state = 0.16 and 0.37 for doxycycline and roxithromycin respectively; pp=0.04).ConclusionsAlthough the efficacy of doxycycline and roxithromycin in sinonasal mucus in vivo cannot be predicted solely from reported minimum inhibitory concentrations, given the added complication of bacterial biofilm antimicrobial tolerance, these results suggest that low mucosal penetration of antibiotics may be one of the factors contributing to the limited efficacy of these agents in the treatment of CRS.

Background The aim of this study was to use computational fluid dynamics (CFD) to investigate the effects on nasal heat exchange and humidification of two different surgical techniques for reducing the inferior turbinate under different environmental conditions. Methods Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Post inferior turbinoplasty 3) Post total inferior turbinate resection (ITR). Two representative healthy models were included. Three different environmental conditions were investigated 1) ambient air 2) cold, dry air 3) hot, humid air. CFD modelling of airflow and conditioning was performed under steady-state, laminar, inspiratory conditions. Findings Nasal conditioning is significantly altered following inferior turbinate reduction surgery, particularly with ITR under cold, dry inspired air (CDA). The degree of impairment is minor under the simulated range of environmental conditions (temperature = 12–40 °C; relative humidity = 13–80%). Streams of significantly colder air are found in the nasopharynx and more prevalent under CDA in ITR. These are related to high velocity flow streams, which remain cool in their centre throughout the widened inferior nasal cavity. Interpretation Reduced air-mucosal heat exchange and moisture carrying capacity occurs under cooler temperatures in patients following inferior turbinate surgery. The clinical impact in extremely cold and dry conditions in groups with poor baseline respiratory function, respiratory illness, or endurance athletes is of special interest.

BACKGROUND The aim of this study was to investigate using computational fluid dynamics (CFD) the effects on nasal aerodynamics of two different techniques for reducing the inferior turbinate. This may assist in surgical planning to select the optimal procedure. METHODS Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Three bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Bilateral inferior turbinoplasty 3) Bilateral total inferior turbinate resection (ITR). Two representative healthy models were included. CFD modeling of airflow was performed under steady-state, laminar, inspiratory conditions. RESULTS Nasal airway resistance was slightly more reduced following ITR compared to turbinoplasty due to loss of the pressure gradient at the head of the IT. Turbinoplasty resulted in ventilation, pressure and wall shear stress profiles closer to those of healthy models. A more prominent jet-like course of the main flow stream was observed inferiorly in the ITR group. CONCLUSIONS Nasal air conditioning was significantly altered following IT surgery. Overall differences between the groups were small and are unlikely to bear influence on nasal function in normal environments. Further studies using a larger number of patients and healthy subjects are required, attempting to establish a clinical correlation with long-term outcomes such as the perception of nasal patency, mucosal crusting and drying, and air conditioning in different environments. Since a large proportion of IT mucosa remains following turbinoplasty, future dependence on topical therapy should also be considered.

Background Despite functional endoscopic sinus surgery (FESS) being the standard of care in medically recalcitrant chronic rhinosinusitis (CRS), its effect on sinus ventilation has not been fully characterized. Airflow simulations can help improve our understanding of how surgical strategies affect post-surgical sinus ventilation. Methods Eight postoperative sinonasal cavity models were reconstructed from a wide spectrum of CRS patients who had undergone FESS. Computational fluid dynamics modeling of steady-state, laminar, inspiratory airflow was performed. Ventilation was quantified and observed for all the sinuses in each model. Results Sinus aeration was enhanced following FESS, particularly in the maxillary and ethmoid sinuses. The degree of improvement was related to the extent of surgery performed. This finding was accentuated at a higher inhalational flow rate of 15L/min. The relationship between ostium size and corresponding sinus inflow was stronger for the maxillary and sphenoid sinuses. Maxillary inflow reached 50% in a mega-antrostomy patient, while negligible flow occurred in the frontal sinuses for except one whom had undergone a modified Lothrop procedure. Conclusions This study has quantified sinus airflow in the largest set of post-FESS patients to date, to show that with increasing extensive surgery, the sinus and nasal cavity become more interconnected and functionally interdependent. Accordingly, sinus ventilation is improved. This may have important consequences for pre- and post-surgical assessment and planning, and on predicting how drug delivery treatments and devices can be designed to target the postoperative sinuses.

BackgroundThe evidence supporting the efficacy of antibiotic therapy in the treatment of chronic rhinosinusitis is not compelling. A limited number of studies show that the changes in the nasal microbiome in patients following drug therapy are unpredictable and variable. The evidence for the impact of oral antibiotics on the gut microbiota is stronger, possibly as a result of differences in drug distribution to various sites around the body. There are few studies on sinus mucosal and mucus levels of oral antibiotics used in the treatment of chronic rhinosinusitis. The distribution dependent effects of antibiotics on the sinonasal microbiome is unclear.ConclusionThis review highlights that relative drug concentrations and their efficacy on microbiota at different sites is an important subject for future studies investigating chronic rhinosinusitis.

BACKGROUND Optimizing intranasal distribution and retention of nasal sprays is essential in the management of patients with chronic rhinosinusitis (CRS), including those that have had functional endoscopic sinus surgery (FESS). Despite multiple existing distribution studies, there remains a need for a technique that allows regionalization of particle deposition within a patient's unique 3-dimensional (3D) geometry without exposing the patient to radiation. METHODS Seven participants delivered normal saline containing a gadolinium-based contrast agent (GBCA) by either saline irrigation or nasal sprays on 1 side of the nasal cavity. The saline irrigation group included 2 participants (both healthy) while the nasal spray group included 5 participants (2 healthy, 2 post-FESS patients, 1 CRS patient without any sinus surgery). The distribution of new signal enhancement was assessed on each participant using magnetic resonance imaging (MRI). Serial scans were performed over an interval of 4 minutes in the nasal spray group to assess changes in intranasal distribution over time. RESULTS Signal enhancement was widespread within the nasal cavities and maxillary sinuses of participants (both healthy) that underwent sinus irrigation. For the nasal spray participants, the hotspots for signal enhancement were similar regardless of disease status or previous history of surgery. These included the internal nasal valve, anterior septum, inferior surface of the inferior turbinate, nasal floor, and nasopharynx. No signal enhancement was detected with nasal sprays in either unoperated or operated paranasal sinuses. CONCLUSION A technique has been developed using MRI evaluation of radioopaque contrast to characterize the temporospatial distribution of topical drug delivery within the sinonasal cavities.

Background The quality of instruments and surgical expertise in minimally invasive surgery has developed markedly in the last two decades. Attention is now being turned to ways to allow surgeons to adopt more cost-effective and environmental-friendly approaches. This review explores current evidence on the cost and environmental impact of reusable versus single-use instruments. In addition, we aim to compare their quality, functionality and associated clinical outcomes. Method The Medline and EMBASE databases were searched for relevant literature from January 2000 to May 2015. Subject headings were Equipment Reuse/, Disposable Equipment/, Cholecystectomy/, Laparoscopic/, Laparoscopy/, Surgical Instruments/, Medical Waste Disposal/, Waste Management/, Medical Waste/, Environmental Sustainability/ and Sterilization/. Results There are few objective comparative analyses between single-use versus reusable instruments. Current evidence suggests that limiting use of disposal instruments to necessity may hold both economical and environmental advantages. Theoretical advantages of single-use instruments in quality, safety, sterility, ease of use and importantly patient outcomes have rarely been examined. Cost-saving methods, environmental-friendly methods, global operative costs, hidden costs, sterilization methods and quality assurance systems vary greatly between studies making it difficult to gain an overview of the comparison between single-use and reusable instruments. Conclusions Further examination of cost comparisons between disposable and reusable instruments is necessary while externalized environmental costs, instrument function and safety are also important to consider in future studies.

Background The importance of non-technical skills in improving surgical safety and performance is now well recognised. Better understanding is needed of the impact that non-technical skills of the multi-disciplinary theatre team have on intra-operative incidents in the operating room (OR) using structured theatre-based assessment. The interaction of non-technical skills that influence surgical safety of the OR team will be explored and made more transparent. Methods Between May–August 2013, a range of procedures in general and vascular surgery in the Royal Infirmary of Edinburgh were performed. Non-technical skills behavioural markers and associated intra-operative incidents were recorded using established behavioural marking systems (NOTSS, ANTS and SPLINTS). Adherence to the surgical safety checklist was also observed. Results A total of 51 procedures were observed, with 90 recorded incidents – 57 of which were considered avoidable. Poor situational awareness was a common area for surgeons and anaesthetists leading to most intra-operative incidents. Poor communication and teamwork across the whole OR team had a generally large impact on intra-operative incidents. Leadership was shown to be an essential set of skills for the surgeons as demonstrated by the high correlation of poor leadership with intra-operative incidents. Team-working and management skills appeared to be especially important for anaesthetists in the recovery from an intra-operative incident. Conclusion A significant number of avoidable incidents occur during operative procedures. These can all be linked to failures in non-technical skills. Better training of both individual and team in non-technical skills is needed in order to improve patient safety in the operating room.

Optimizing intranasal distribution and retention of topical therapy is essential in the management of patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). Computational fluid dynamics analysis has not previously been used to investigate sinus nasal spray delivery in the complete post-operative sinonasal geometries of patients who have undergone FESS. Models of sinonasal cavities were created from postoperative magnetic resonance imaging scans in four patients, three of whom underwent a comprehensive FESS, the other a modified endoscopic Lothrop procedure. Spray simulations were conducted at different flow rates (5 L/min, 10 L/min and 15 L/min) using sixteen particle sizes ranging from 4 μm to 70μm, spray velocity of 10 m/s and plume angle of 15°. Two different spray insertion angles were compared. Airflow distribution in the sinuses was closely related to the patient's nasal geometry and surgical intervention, in particular a unique crossflow between nasal chambers was present for the Lothrop patient. Sinus deposition was generally more effective with inhalational transport of low-inertia particles outside of the range produced by many standard nasal sprays or nebulizer. This was true except in the Lothrop patient, since previous surgery had been performed removing most of the septum where high-inertia particles would normally deposit. For sinuses receiving minimal airflow, particle penetration was diminished and successful deposition in the region became more restricted by device parameters. Further research is needed to validate these findings and explore other spray variables in a wider spectrum of patients to ascertain a multi-level approach to optimizing drug delivery in the sinuses.

ObjectivesMajor hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.MethodsThe MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were ‘hepatectomy/’, ‘liver function/’, ‘liver failure/’ and ‘physiology/’.ResultsPredictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.ConclusionsThe pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.

Background: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and make up 1–2% of all gastrointestinal malignancies. Traditionally, the treatment of choice for primary disease is surgical resection; however, no single surgeon or institution gets extensive exposure to these patients so appropriate decision-making is difficult, particularly since the introduction of the tyrosine kinase inhibitor imatinib, which has become an important additional management tool. Method: All patients were diagnosed and treated for GISTs in Christchurch Hospital (Christchurch, New Zealand) between 1 January 2000 and 31 December 2010. We maintain a prospective database of all patients with GISTs. Data on clinical and histopathological variables, management and survival outcomes were recorded. These were then reviewed. Results: There were 93 patients in this study. Fifty were women. Median age was 69 (interquartile range (IQR) 59–76) years. Fifty-one tumours were located in the stomach, 27 in the small bowel, six in the colon, three in the oesophagus, one in the rectum and five were extra-gastrointestinal. In total, 22 patients received imatinib therapy; four patients with metastatic disease had imatinib as sole therapy. The median follow-up was 58 (IQR 30–90) months. The 5-year overall survival and disease-free survival (DFS) for the entire study population was 69% and 64%, respectively. The 5-year DFS was higher for all patients who have localized disease when compared with those who have metastatic disease (76% versus 28%, P-value 0.001). Conclusion: Surgery aiming at an R0 resection remains the mainstay of treatment. We propose the most effective way to grow the knowledge base in New Zealand is the establishment of a national register, thereby allowing better clinical decision-making by interpretation of a larger data set.

The quality of instruments and surgical expertise in minimally invasive surgery has developed markedly in the last two decades. Attention is now being turned to ways to allow surgeons to adopt more cost-effective and environmental-friendly approaches. This review explores current evidence on the cost and environmental impact of reusable versus single-use instruments. In addition, we aim to compare their quality, functionality and associated clinical outcomes.The Medline and EMBASE databases were searched for relevant literature from January 2000 to May 2015. Subject headings were Equipment Reuse/, Disposable Equipment/, Cholecystectomy/, Laparoscopic/, Laparoscopy/, Surgical Instruments/, Medical Waste Disposal/, Waste Management/, Medical Waste/, Environmental Sustainability/ and Sterilization/.There are few objective comparative analyses between single-use versus reusable instruments. Current evidence suggests that limiting use of disposal instruments to necessity may hold both economical and environmental advantages. Theoretical advantages of single-use instruments in quality, safety, sterility, ease of use and importantly patient outcomes have rarely been examined. Cost-saving methods, environmental-friendly methods, global operative costs, hidden costs, sterilization methods and quality assurance systems vary greatly between studies making it difficult to gain an overview of the comparison between single-use and reusable instruments.Further examination of cost comparisons between disposable and reusable instruments is necessary while externalized environmental costs, instrument function and safety are also important to consider in future studies.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and make up 1-2% of all gastrointestinal malignancies. Traditionally, the treatment of choice for primary disease is surgical resection; however, no single surgeon or institution gets extensive exposure to these patients so appropriate decision-making is difficult, particularly since the introduction of the tyrosine kinase inhibitor imatinib, which has become an important additional management tool.All patients were diagnosed and treated for GISTs in Christchurch Hospital (Christchurch, New Zealand) between 1 January 2000 and 31 December 2010. We maintain a prospective database of all patients with GISTs. Data on clinical and histopathological variables, management and survival outcomes were recorded. These were then reviewed.There were 93 patients in this study. Fifty were women. Median age was 69 (interquartile range (IQR) 59-76) years. Fifty-one tumours were located in the stomach, 27 in the small bowel, six in the colon, three in the oesophagus, one in the rectum and five were extra-gastrointestinal. In total, 22 patients received imatinib therapy; four patients with metastatic disease had imatinib as sole therapy. The median follow-up was 58 (IQR 30-90) months. The 5-year overall survival and disease-free survival (DFS) for the entire study population was 69% and 64%, respectively. The 5-year DFS was higher for all patients who have localized disease when compared with those who have metastatic disease (76% versus 28%, P-value 0.001).Surgery aiming at an R0 resection remains the mainstay of treatment. We propose the most effective way to grow the knowledge base in New Zealand is the establishment of a national register, thereby allowing better clinical decision-making by interpretation of a larger data set.