Remote Training of Functional Endoscopic Sinus Surgery With Advanced Manufactured 3D Sinus Models and a Telemedicine System.

Objective: Traditionally, cadaveric courses have been an important tool in surgical education for Functional Endoscopic Sinus Surgery (FESS). The recent COVID-19 pandemic, however, has had a significant global impact on such courses due to its travel restrictions, social distancing regulations, and infection risk. Here, we report the world-first remote (Functional Endoscopic Sinus Surgery) FESS training course between Japan and Australia, utilizing novel 3D-printed sinus models. We examined the feasibility and educational effect of the course conducted entirely remotely with encrypted telemedicine software. Methods: Three otolaryngologists in Hokkaido, Japan, were trained to perform frontal sinus dissections on novel 3D sinus models of increasing difficulty, by two rhinologists located in Adelaide, South Australia. The advanced manufactured sinus models were 3D printed from the Computed tomography (CT) scans of patients with chronic rhinosinusitis. Using Zoom and the Quintree telemedicine platform, the surgeons in Adelaide first lectured the Japanese surgeons on the Building Block Concept for a three Dimensional understanding of the frontal recess. They in real time directly supervised the surgeons as they planned and then performed the frontal sinus dissections. The Japanese surgeons were asked to complete a questionnaire pertaining to their experience and the time taken to perform the frontal dissection was recorded. The course was streamed to over 200 otolaryngologists worldwide. Results: All dissectors completed five frontal sinusotomies. The time to identify the frontal sinus drainage pathway (FSDP) significantly reduced from 1,292 ± 672 to 321 ± 267 s (p = 0.02), despite an increase in the difficulty of the frontal recess anatomy. Image analysis revealed the volume of FSDP was improved (2.36 ± 0.00 to 9.70 ± 1.49 ml, p = 0.014). Questionnaires showed the course's general benefit was 95.47 ± 5.13 in dissectors and 89.24 ± 15.75 in audiences. Conclusion: The combination of telemedicine software, web-conferencing technology, standardized 3D sinus models, and expert supervision, provides excellent training outcomes for surgeons in circumstances when classical surgical workshops cannot be realized.

The Use of Postoperative Antibiotics Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

BACKGROUND: Endoscopic sinus surgery is performed for medically recalcitrant chronic rhinosinusitis. There is no universally accepted strategy regarding post-operative antibiotics despite the high rates of usage worldwide. The aim of this study was to analyse patient-reported and objective outcomes behind antibiotic use following endoscopic sinus surgery. METHODS: A search of electronic databases was performed. Eligible randomised controlled trials (RCTs) and observational trials were included. The primary outcome was patient reported outcome measures. Secondary outcomes were local infections, endoscopy scores and adverse events. Meta-analysis was performed. RESULTS: Of 1045 publications identified, 7 were included in the qualitative synthesis and 5 RCTs were included in meta-analysis. Antibiotic regimens varied between studies in terms of antibiotic selection, timing commenced and duration of use. Meta-analysis suggested no significant difference between placebo and antibiotics in patient reported outcome measures (standardised mean difference (SMD) -0.215, 95% confidence interval (CI) -0.637 to 0.207) or endoscopic scores (SMD -2.86, 95% CI -0.846 to 0.273). There was no consistent definition in reporting of infection; therefore, this outcome cannot be comprehensively considered. No severe adverse events were attributable to antibiotics. CONCLUSIONS: From the studies analysed, there is no level 1 evidence to suggest that antibiotics improved patient outcomes following sinus surgery. However, there was significant heterogeneity in outcome measures and no clear data exists regarding the effects of antibiotics on postoperative infections. The available evidence at present is not enough to make a recommendation in either direction. Further designed larger RCTs are required to investigate these questions in more detail.

Staphylococcus aureus biofilm exoproteins are cytotoxic to human nasal epithelial barrier in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis patients (CRS) suffer from chronic inflammation of the sinus mucosa associated with chronic relapsing infections. Mucosal biofilms, associated with Staphylococcus aureus, have been implicated as a cause. We compared the effect of exoproteins secreted from clinical isolates of S aureus from CRS patients in planktonic and biofilm form on the nasal epithelial barrier. METHODS: Clinical S aureus isolates from 39 CRS patients were grown in planktonic and biofilm forms and their exoproteins concentrated. These were applied to primary human nasal epithelial cells grown at the air-liquid interface. Transepithelial electrical resistance, permeability of flourescein isothiocyanate-dextrans, and cytotoxicity were measured. Structure and expression of tight junctions zona occludens-1, and claudin-1 proteins were assessed by electron microscopy and immunofluorescence. The Wilcoxon signed rank test was used for statistical analyses. RESULTS: S aureus biofilm exoproteins showed dose- and time-dependent reduction of transepithelial electrical resistance, increased cell toxicity, and increased permeability (p < 0.001) compared with equal concentrations of planktonic cultures. Discontinuity in zona occludens-1 and claudin-1 immunofluorescence was confirmed as disrupted tight junctions on electron microscopy. CONCLUSION: S aureus biofilm exoproteins disrupt the mucosal barrier structure in a time- and dose-dependent manner and are toxic. Damage to the mucosal barrier by S aureus biofilm exoproteins may play a major role in CRS etiopathogenesis.

In vitro safety evaluation of a povidone-iodine solution applied to human nasal epithelial cells.

BACKGROUND: Nasal topical treatments can provide an effective method of disease control for patients suffering from chronic rhinosinusitis (CRS). However, some frequently used formulations lack adequate evaluation on their safety. This study investigated the effect of 0.5% povidone-iodine (Nasodine) on the sinonasal epithelial barrier and ciliated human nasal epithelial cells (HNECs) in vitro. METHODS: Nasodine was applied to air-liquid interface (ALI) cultures of primary HNECs from CRS patients. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER), paracellular permeability, and immunolocalization of the zona occludens-1 (ZO-1) tight junction protein. Toxicity and ciliary beat frequency (CBF) were also studied. RESULTS: Nasodine was not toxic and did not have detrimental effects on the paracellular permeability or CBF. Nasodine did not show a significant reduction in TEER with a 5-minute exposure; however, with a 30-minute exposure there was a significant reduction in TEER at 1 hour and at 4 hours after exposure. CONCLUSION: Application of Nasodine to HNEC-ALI cultures in vitro for up to 30 minutes was not toxic and did not affect the paracellular permeability or CBF.

A Novel Rat Model to Test Intra-Abdominal Anti-adhesive Therapy.

Background: Adhesion formation after abdominal surgery is considered almost inevitable and a major cause of morbidity. Novel treatments have been proposed, however there is a lack of suitable small animal models for pre-clinical evaluation, mainly due to inconsistency in adhesion formation in positive control animals. Here, we propose a new rat model of abdominal adhesions using Kaolin as the adhesion-inducing agent at an optimized dosage for testing newer agents in respect to their anti-adhesive property. Materials and Methods: Twenty-five adult (8-10 week old) male Wistar albino rats underwent midline laparotomy and caecal abrasion and were randomized to receive topical applications of normal saline or different concentrations and volumes of a Kaolin-based formulation. At day 14 rats were humanely killed, and adhesions graded macroscopically by an investigator blinded to the treatment groups, using pre-determined adhesion scores and microscopically using histopathology. Results: Kaolin at 0.005 g/mL caused consistent adhesions without compromising rat viability. At higher doses significant morbidity and mortality was observed in the animals treated. Conclusions: Kaolin induced adhesion in a rat abdominal surgery model is reliable and can be safely used to test the efficacy of novel anti-adhesive formulations to prevent intra-abdominal adhesions.

Endoscopic transnasal repair of two cases of spontaneous cerebrospinal fluid fistula in the foramen rotundum.

We report two female patients aged 16 and 33 who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhoea. Beta-2 transferrin was positive in both cases. Initial high-resolution CT showed fluid in the maxillary sinus but no obvious bony defect. MR imaging revealed maxillary sinus cysts with high signal on T2 sequences. Endoscopic transnasal surgery with intrathecal fluorescein was undertaken and in both cases a leak was identified from foramen rotundum and repaired. Both patients are symptom free at 6 months. These cases highlight the rare occurrence of spontaneous CSF leak from the foramen rotundum, and how they can be effectively repaired using the endoscopic transnasal approach.

Successful repair of intraoperative cerebrospinal fluid leaks improves outcomes in endoscopic skull base surgery.

BACKGROUND: The impact of failed cerebrospinal fluid leak (CSF) leak repair in endoscopic skull base surgery has not been adequately studied. METHODS: In this investigation we reviewed patients who had undergone endoscopic skull base surgery between 2002 and 2014 at 7 international centers. Demographic variables, comorbidities, tumor characteristics, and repair techniques were evaluated to determine association with successful repair of CSF leak. Postoperative complications and length of stay were compared among groups. RESULTS: Data were collected on 2097 patients who were divided into 3 groups: (1) those with no intraoperative leak (n = 1533); (2) those with successful repair of their intraoperative leak (n = 452); and (3) those with failed repair (n = 112). Compared with successful repair, failed repair was associated with an increased risk of intracranial infection (odds ratio [OR], 5.6; 95% confidence interval [CI], 5.3-13.15), pneumocephalus (OR, 16; 95% CI, 5.8-44.4), 30-day readmission (OR, 8.4; 95% CI, 5.3-13.5), reoperation (OR, 115.4; 95% CI, 56.3-236.8), and prolonged hospital stay (14.9 vs 7.0 days, p < 0.01). Outcomes in patients who had successful repairs of intraoperative leaks were similar to those who never had leakage. Intraoperative use of pedicled nasoseptal flaps was associated with successful repair (OR, 0.60; 95% CI, 0.34-0.92). CONCLUSION: Intraoperative CSF leaks are a frequent and expected occurrence during endoscopic skull base surgery. Failed CSF leak repair has a significant impact on patient outcomes, with increased rates of postoperative pneumocephalus, intracranial infections, reoperation, deep vein thrombosis, readmission, and prolonged hospital stay. Recognition and repair of intraoperative CSF leaks reduces postoperative complications. Use of pedicled nasoseptal flaps improves outcomes in reconstructing defects at higher risk for postoperative leak.

Chronic Rhinosinusitis with Polyps Is Characterized by Increased Mucosal and Blood Th17 Effector Cytokine Producing Cells.

Background: Recent studies have implied a role for Th17 cells in CRS with nasal polyps (CRSwNP) patients. However, the capacity of these cells to produce Th17 cytokines is still unknown. Here we sought to quantify IL-17A, IL-17F, IL-21, and IL-22 cytokines produced by Th17 cells in mucosal tissue and peripheral blood of CRSwNP, CRS without nasal polyps (CRSsNP) and control patients. Methods: Samples were prospectively collected from CRS patients and non-CRS controls. We used flow cytometry to characterize the Th17 cells and their cytokines in sinonasal tissue and peripheral blood. Results: A total of 36 patients were recruited to the study. CRSwNP patients had significantly more tissue IL-17A (9.53 ± 2.71 vs. 1.11 ± 0.43 vs. 0.77 ± 0.07), IL-17F (4.96 ± 1.48 vs. 0.88 ± 0.31 vs. 0.56 ± 0.04), IL-21 (5.55 ± 2.01 vs. 1.60 ± 0.71 vs. 1.53 ± 0.55) and IL-22 (4.73 ± 1.58 vs. 0.70 ± 0.28 vs. 0.88 ± 0.26) producing Th17 cells compared to CRSsNP and control mucosa per mg of tissue, respectively. Allergic CRSwNP patients had decreased numbers of IL-21 producing Th17 cells compared to non-Allergic CRSwNP. (1.69 ± 0.57 vs. 9.41 ± 3.23) per mg of tissue, respectively (Kruskal-Wallis p < 0.05). Conclusion: In summary our study identified increased numbers of IL-17A, IL-17F, IL-21 and IL-22 positive Th17 cells in CRSwNP patient polyps and peripheral blood suggesting an altered activation state of those cells both locally and systemically. Atopic CRSwNP had decreased amounts of tissue Th17 cell derived IL-21 implying a potential protective role for IL-21 in CRSwNP allergic inflammation.

Reduced Innate Immune Response to a Staphylococcus aureus Small Colony Variant Compared to Its Wild-Type Parent Strain.

Background:Staphylococcus aureus (S. aureus) small colony variants (SCVs) can survive within the host intracellular milieu and are associated with chronic relapsing infections. However, it is unknown whether host invasion rates and immune responses differ between SCVs and their wild-type counterparts. This study used a stable S. aureus SCV (WCH-SK2SCV) developed from a clinical isolate (WCH-SK2WT) in inflammation-relevant conditions. Intracellular infection rates as well as host immune responses to WCH-SK2WT and WCH-SK2SCV infections were investigated. Method: NuLi-1 cells were infected with either WCH-SK2WT or WCH-SK2SCV, and the intracellular infection rate was determined over time. mRNA expression of cells infected with each strain intra- and extra-cellularly was analyzed using a microfluidic qPCR array to generate an expression profile of thirty-nine genes involved in the host immune response. Results: No difference was found in the intracellular infection rate between WCH-SK2WT and WCH-SK2SCV. Whereas, extracellular infection induced a robust pro-inflammatory response, intracellular infection elicited a modest response. Intracellular WCH-SK2WT infection induced mRNA expression of TLR2, pro-inflammatory cytokines (IL1B, IL6, and IL12) and tissue remodeling factors (MMP9). In contrast, intracellular WCH-SK2SCV infection induced up regulation of only TLR2. Conclusions: Whereas, host intracellular infection rates of WCH-SK2SCV and WCH-SK2WT were similar, WCH-SK2SCV intracellular infection induced a less widespread up regulation of pro-inflammatory and tissue remodeling factors in comparison to intracellular WCH-SK2WT infection. These findings support the current view that SCVs are able to evade host immune detection to allow their own survival.

Anatomical landmarks of the lateral nasal wall: implications for endonasal lacrimal surgery.

PURPOSE OF REVIEW: An accurate understanding of the anatomy of the lateral nasal wall is key to achieving complete exposure of the lacrimal sac during endonasal dacryocystorhinostomy (EnDCR) and the avoidance of complications such as basal skull fracture and orbital fat prolapse. This review provides a comprehensive summary of the clinical and cadaveric anatomical studies of the lateral nasal wall to date and their application to endonasal lacrimal surgery. RECENT FINDINGS: The maxillary line and the axilla of the middle turbinate are the major landmarks commonly utilized by lacrimal surgeons to localize the lacrimal sac. Numerous clinical, cadaveric and radiologic studies have attempted to define the relationship of these and other important anatomical landmarks, closely related to the lacrimal sac and routinely encountered during endonasal surgery, such as the frontal process of the maxilla, the agger nasi air cell and the uncinate process. A greater understanding of the relevant endonasal anatomy over time has led to safer and more effective surgical techniques. SUMMARY: Greater insights into the precise anatomical relationship of the lacrimal sac to other structures on the lateral nasal wall has enabled lacrimal surgeons to perform EnDCR surgery in a more accurate, efficient and well tolerated manner, matching its success to that of the external approach.

Characterization of the in vivo host response to a bi-labeled chitosan-dextran based hydrogel for postsurgical adhesion prevention.

In developing a chitosan/dextran-based (CD) hydrogel as an adhesion prevention postsurgical aid, the in vivo biodegradation rate, biodistribution, and inflammatory response are important parameters to the biomedical device design. Herein, for the first time, a CD hydrogel was prepared by mixing aqueous solutions of a near infrared (NIR) labeled succinylated chitosan (SC) and tritiated [(3) H] oxidized dextran (DA). The biodegradation and biodistribution of the NIR/[(3) H]-CD hydrogel was tracked noninvasively using NIR fluorescence imaging, and by liquid scintillation counting (LSC) of organs/tissues after subcutaneous injection in BALB/c mice. The inflammatory response was assessed by measuring serum cytokine levels using a Bio-plex assay and by histological examination of injection site tissue. Fluorescence imaging showed the hydrogel to degrade in under a week. LSC revealed the hydrogel to reside mainly at the injection site, and excreted primarily via the urine within the first 48 h. The CD hydrogel showed a mild inflammatory response as cytokine levels were comparable to saline injected controls. Histological examination of injection site tissue confirmed the cytokine results. In summary, the CD hydrogel's in vivo biodegradation rate, biodistribution, and inflammatory response was determined. Our results indicate that the CD hydrogel has an appropriate biocompatibility after s.c. administration.

Endoscopic assessment of the dacryocystorhinostomy ostium after powered endoscopic surgery: behaviour beyond 4 weeks.

BACKGROUND: This study aims to assess the shrinkage of dacryocystorhinostomy (DCR) ostium beyond 4 weeks. DESIGN: Prospective series in a University setting. PARTICIPANTS: Sixty consecutive patients. METHODS: Prospectively collected data of 60 consecutive powered endoscopic DCRs performed in 57 patients over a period of 10 years from 2002 to 2011. All patients had regular follow-up of 2 years post-surgery. The ostium size at 4 weeks, 6 months, 1 year and 2 years were evaluated. Analysis of variance was used to compare the differences. MAIN OUTCOME MEASURE: Changes in ostium measurements. RESULTS: The ostium measured 11.25 mm (standard deviation [SD] = 1.7; 95% confidence intervals [CI] = 10.80-11.69) × 7.07 (SD = 1.4; 95% CI = 6.71-7.42) at 4 weeks. It measured 10.48 mm (SD = 1.6; 95% CI = 10.06-10.90) × 6.65 mm (SD = 1.2; 95% CI = 6.34-6.95) at 6 months, 10.22 mm (SD = 1.5; 95% CI = 9.81-10.61) × 6.52 mm (SD = 1.2; 95% CI = 6.20-6.80) at 1 year and 10.15 mm (SD = 1.5; 95% CI = 9.76-10.53) × 6.45 mm (SD = 1.2; 95% CI = 6.14-6.75). There was no statistically significant decrease in either the ostium size or the area up to 2 years following surgery. CONCLUSION: The ostium achieved using the powered endoscopic DCR technique remains stable in size from 4 weeks to 2 years post-surgery. This likely reflects the advantages of this technique which facilitates healing by primary intention.

The use of chitosan-dextran gel shows anti-inflammatory, antibiofilm, and antiproliferative properties in fibroblast cell culture.

BACKGROUND: Chitosan-dextran gel has been used as an antihemostatic agent and antiadhesive agent after endoscopic sinus surgery. Because Staphylococcus aureus biofilms have been implicated in recalcitrant chronic rhinosinusitis, this study aimed to further investigate the (i) anti-inflammatory, (ii) bacterial biofilm inhibition, (iii) antiproliferative effects, and (iv) wound-healing properties of chitosan and chitosan-dextran gel. METHODS: Fibroblasts were isolated from human nasal tissue and were used to determine the effects of chitosan and chitosan-dextran gel on (i) cell proliferation, (ii) wound healing, (iii) inflammation in fibroblast cultures challenged with superantigens S. aureus enterotoxin B (SEB) and toxic shock syndrome toxin (TSST), and (iv) on S. aureus biofilms. RESULTS: Chitosan was highly effective at reducing IL-8 expression after TSST and SEB challenge. Chitosan was also effective at reducing IL-8 expression of nonchallenged fibroblasts showing its anti-inflammatory effects on fibroblasts in a diseased state. Chitosan-dextran gel showed strong antibiofilm properties at 50% (v/v) concentration in vitro. Dextran, on its own, showed antibiofilm properties at 1.25% (w/v) concentration. Chitosan, on its own, reduced proliferation of fibroblasts to 82% of control proliferation and chitosan-dextran gel reduced proliferation of the fibroblasts to 0.04% of control proliferation. Relative to the no treatment controls, chitosan-dextran gel significantly delayed the wound-healing rate over the first 48 hours of the experiment. CONCLUSION: Chitosan-dextran gel reduced fibroblast proliferation and wound-healing time, showing a possible mechanism of reducing adhesions in the postsurgical period. Chitosan reduced IL-8 levels, showing its anti-inflammatory properties. Chitosan-dextran gel and dextran treatment showed antibiofilm properties in our model.

Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention.

An amine-functionalized succinyl chitosan and an oxidized dextran were synthesized and mixed in aqueous solution to form an in situ chitosan/dextran injectable, surgical hydrogel for adhesion prevention. Rheological characterization showed that the rate of gelation and moduli were tunable based on amine and aldehyde levels, as well as polymer concentrations. The CD hydrogels have been shown to be effective post-operative aids in prevention of adhesions in ear, nose, and throat surgeries and abdominal surgeries in vivo. In vitro biocompatibility testing was performed on CD hydrogels containing one of two oxidized dextrans, an 80 % oxidized (CD-100) or 25 % (CD-25) oxidized dextran. However, the CD-100 hydrogel showed moderate cytotoxicity in vitro to Vero cells. SC component of the CD hydrogel, however, showed no cytotoxic effect. In order to increase the biocompatibility of the hydrogel, a lower aldehyde level hydrogel was developed. CD-25 was found to be non-cytotoxic to L929 fibroblasts. The in vivo pro-inflammatory response of the CD-25 hydrogel, after intraperitoneal injection in BALB/c mice, was also determined by measuring serum TNF-α levels and by histological analysis of tissues. TNF-α levels were similar in mice injected with CD-25 hydrogel as compared to the negative saline injected control; and were significantly different (P < 0.05) as compared to the positive, lipopolysaccharide, injected control. Histological examination revealed no inflammation seen in CD hydrogel injected mice. The results of these in vitro and in vivo studies demonstrate the biocompatibility of the CD hydrogel as a post-operative aid for adhesion prevention.

Management of functional epiphora in patients with an anatomically patent dacryocystorhinostomy.

IMPORTANCE: Approximately 5% to 10% of patients continue to experience persistent epiphora following an anatomically successful dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction or stenosis. OBJECTIVE: To investigate the management and success rate of so-called "functional failure" of DCR for nasolacrimal duct obstruction by experienced lacrimal surgeons. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective case series including 5 Australian and New Zealand centers. Participants included 61 patients (71% women [n = 46]; mean age, 66 years) with functional epiphora after 65 DCRs (69% transnasal) who were recruited over a mean of 7.6 years. Inclusion criteria included confirmed preoperative diagnosis of nasolacrimal duct obstruction or stenosis, age greater than 18 years, recurrent or persistent epiphora after DCR, an anatomically successful DCR, and follow-up longer than 6 months. Exclusion criteria included evidence of lacrimal hypersecretion, eyelid malposition, and punctal or canalicular abnormalities. MAIN OUTCOMES AND MEASURES: The number, type, timing, and success of all clinical interventions performed for the management of functional epiphora after DCR. RESULTS: Epiphora recurred a mean of 8.9 months after primary DCR; 89% of the cases (n = 58) had evidence of a patent ostium and 100% were patent on lacrimal irrigation. Intubation with a lacrimal stent was performed in 82% of the cases at the time of surgery, and all stents were removed a mean of 8 weeks postoperatively. Epiphora was reported immediately following DCR in 32% (n = 21) of the cases and within 6 weeks after removal of the stent in 31% (n = 20); late recurrence (>12 months after DCR) developed in 37% (n = 24) of the cases. In a total of 15% of the cases, participants declined any treatment following DCR. The remainder underwent a mean of 1.3 interventions (range, 1-3) during a mean of 23 to 41 months after primary DCR, following which 72% (n = 47) of the cases had a successful outcome; 12% (n = 8) failed to achieve improvement, and the patients declined further intervention. Thirty-nine interventions (60%) were intubation with a silicone stent with a 54% success rate. Almost half of those undergoing intubation elected to keep the stent permanently; 34% (n = 22) had an eyelid-tightening procedure with 50% success, and 15% (n = 10) required a Lester-Jones tube despite patent canaliculi, with a success rate of 90%. CONCLUSIONS AND RELEVANCE: Functional epiphora after DCR among patients with preoperative nasolacrimal duct obstruction or stenosis appears to be uncommon. Benefits can be achieved in most patients with intubation (transient or permanent) or eyelid tightening. More than one procedure is often required.

Long-term outcomes for the endoscopic modified Lothrop/Draf III procedure: a 10-year review.

OBJECTIVES/HYPOTHESIS: To detail the long-term outcomes of the endoscopic modified Lothrop procedure (EMLP) (also know as Draf III/frontal drillout) and identify key risk factors for failure. STUDY DESIGN: Retrospective cohort study and chart review. METHODS: Endoscopic assessment of frontal ostium patency and patient-reported symptoms were prospectively collected on patients who underwent EMLP between January 2001 and December 2011 for chronic rhinosinusitis (CRS). Risk factors for failing EMLP were identified. RESULTS: There were 229 patients who met the inclusion and exclusion criteria and underwent an EMLP. The average number of standard endoscopic sinus surgery procedures prior to an EMLP was 3.8 (95% confidence interval [CI]: 3.4-4.2, standard deviation [SD]: 3.3).The average length of follow-up was 45.0 months (95% CI: 41.2-48.9 months, SD: 22.3 months). The EMLP was successful in 95% (217/229), with no further surgery being required. Postsurgical recurrence of disease with persistence of symptoms requiring revision EMLP occurred in 12 patients. No complications were identified. Allergic fungal sinusitis and recurrent Staphylococcus aureus infections were identified as potential risk factors for failure. CONCLUSIONS: This is the single largest study of EMLP in the literature with a long follow-up period. It illustrates the benefit of the EMLP for patients with CRS recalcitrant to medical and standard endoscopic sinus surgery.

Phl p 1-specific human monoclonal IgE and design of a hypoallergenic group 1 grass pollen allergen fragment.

Detailed understanding of how Abs of the IgE isotype interact with allergen at the onset of an allergic reaction is of great importance for deciphering mechanisms involved in the development of disease and may aid in the design of hypoallergenic variants. In this study, we have used a set of human monoclonal IgE Abs derived from the repertoires of allergic individuals, specific for the major timothy grass pollen allergen Phl p 1, to gain detailed information on the interaction between Abs and allergen. These allergen-specific IgE are to varying degrees cross-reactive toward both different allergen isoforms and various group 1 allergens originating from other grass species. The usage of human monoclonal IgE, as an alternative to polyclonal preparations or mouse Abs, allowed us to locate several important IgE-binding epitopes on the C-terminal domain of Phl p 1, all clustered to an IgE-binding "hot spot." By introducing three mutations in the IgE-binding area of the C-terminal domain we were able to significantly reduce its reactivity with serum IgE. In conclusion, our study shows the great potential of using human monoclonal IgE as a tool for studies of the molecular interactions taking place during allergic responses. Furthermore, we present a novel IgE-hyporeactive fragment with the potential to be used as a safer hypoallergenic alternative in specific immunotherapy than the pollen extracts used today.

Endoscopic endonasal transsphenoidal surgery: a mentoring surgical model.

BACKGROUND: We report the experience of endoscopic endonasal transsphenoidal surgery (EETS) for resection of pituitary region tumours at Wellington, the central regional referral centre for neurosurgery in New Zealand, and discuss the collaborative mentoring surgical model that enhanced the learning experience. METHOD: Between January 2007 and June 2009, a total of 47 operations on 46 patients were performed and reviewed retrospectively. All patients had perioperative clinical assessment, hormonal profile and magnetic resonance imaging studies for residual/recurrent disease. The collaborative model utilized two neurosurgeons with experience in the microsurgical resection of pituitary tumours: an endoscopic skull base fellowship trained rhinologist and an endoscopic skull base rhinologist with more experience who visited twice a year from Adelaide, Australia. RESULTS: The pathology results included: 30 non-functioning pituitary adenomas, 10 secreting pituitary adenomas, 3 meningiomas, 1 chordoma, 1 anterior skull base adenocarcinoma and 1 clival prostate metastasis. Complete tumour resection was intended and achieved in 38 cases. All 10 patients with secreting adenomas achieved improvement of hormonal profile. Nineteen out of 27 cases demonstrated improvement of vision. Perioperative complications included one epistaxis, three cerebrospinal fluid fistulae, one delayed chronic subdural haematoma and one persistent diabetes insipidus. CONCLUSION: Our results highlight the value of a collaborative mentoring surgical model for a single centre adopting the endoscopic transsphenoidal technique and demonstrate that excellent EETS outcomes can be achieved in a smaller endoscopic skull base unit in Australasia during the learning phase.