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Introduction  Olfactory groove meningiomas (OGMs) are often associated with loss of smell following resection. Loss of smell has a measurable impact on quality of life. Smell preservation has been previously described in open approaches for early stage or unilateral OGMs. Evidence of smell preservation in endoscopic approaches is lacking. Design  A multi-institutional retrospective review was performed on consecutive patients who underwent unilateral endoscopic endonasal resection of OGM. A gross total resection was achieved with preservation of the contralateral olfactory cleft and bulb. Olfactory function was assessed with a six-point olfactory symptom score and the Sniffin' Sticks 12-item smell identification test (SS-12). Contralateral olfactory bulb volume was measured on postoperative magnetic resonance imaging. Results  Four patients (age 42.0 ± 7.5, 75% female) were assessed. Olfactory function was assessed at 21.8 ± 5.6 months following surgery. All patients reported some degree of smell preservation (75% described a slight/mild impairment in smell or better). Olfactory identification was preserved with an SS-12 score of 9 ± 1.4 (anosmia defined as ≤6). The olfactory bulb volume was calculated to be 47.4 ± 15.9 mm 3 (normal >40 mm 3 ). Conclusion  Smell preservation is possible following unilateral endoscopic endonasal resection of carefully selected OGM.

Objectives: To determine the clinical utility of assessment of tumour invasion, markers of proliferation, and the French clinicopathological classification in pituitary tumour prognostication. Methods: This is a retrospective evaluation of adult patients undergoing pituitary surgery at Oxford University and St Vincent's Hospitals, between 1989 and 2016, with at least 12 months of clinical data. Invasion was assessed radiologically, proliferative markers (Ki67, mitotic count, p53) by immunohistochemistry. Tumours were graded according to the clinicopathological classification. Intra- and interlaboratory variability of histopathology reporting was evaluated. Outcomes: (1) Tumour recurrence (radiological or reintervention ≥12 months postoperatively) and/or (2) "aggressive behaviour" (≥4 interventions and/or invasive tumour with recurrence/reintervention between 12 and 24 months postoperatively). Results: A total of 386 patients were included, age at surgery was 56 (interquartile range [IQR] 41-67) years, 54% were male, and median followup was 90 months (range 44-126). Tumours were predominantly clinically nonfunctioning (252, 65%), with overall 53% invasive, and 10% that demonstrated ≥2 proliferative marker positivity. Recurrence was predicted by invasiveness (hazards ratio [HR] 1.6 [1.10-2.37], P .02), elevated mitotic count (HR 2.17 [1.21-3.89], P .01), grade (2b vs 1a HR 2.32 [1.06-5.03], P .03), and absence of gross total resection (HR 3.70 [1.72-8.00], P .01). Clinically defined aggressiveness was associated with elevated Ki67, mitotic count, and invasiveness. Ki67 reporting methodologies showed moderate correlation across laboratories (Phi 0.620), whereas p53 reporting reproducibility was poor (Phi 0.146). Conclusions: Proliferative markers, including Ki67 and mitotic count, but not p53, are important in predicting the development of aggressive pituitary tumour behaviour. [ABSTRACT FROM AUTHOR]

Introduction The definition of a delusion is `a false, unshakeable idea or belief ... held with extraordinary conviction and subjective certainty' [1]. Delusions are a common symptom of a range [...]

Objective: The clinical utility and prognostic value of WHO 2017 line-age-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the c linical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the progno stic value of improved lineage-based classification of pituitary tumours. Methods: This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent's Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of ide ntifying 'higher-risk' histological subtypes was assessed. Results: There were 171 patient tumour samples analyzed in the histolog ical cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 2 0/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk hist ological subtype tumours. These were associated with tumour invasiveness (P = 0.050), early recurrence (12-24 months, P = 0.013), shorter median time to recurrence (49 (IQR: 22.5-73.0) vs 15 (IQR: 12.0-25.0) months, P = 0.005) and reduced recurrence-free survival (P = 0.031). Conclusions: Application of transcription factor analysis, in addition to h ormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an imp roved approach to prognostication. [ABSTRACT FROM AUTHOR]

Objective  Despite multidisciplinary care being commonly recommended, there remains limited evidence supporting its benefits in pituitary disease management. This study aimed to assess the impact of multidisciplinary care in pituitary surgery. Methods  A retrospective cohort study was performed comparing pituitary surgery outcomes among consecutive patients within a quaternary referral center in 5 years before and after introduction of a multidisciplinary team (MDT). Primary outcomes were endocrine (transient diabetes insipidus [DI], syndrome of inappropriate antidiuretic hormone [SIADH], and new hypopituitarism) and surgical (cerebrospinal fluid [CSF] leak, epistaxis, intracranial hemorrhage, and meningitis) complications, length of hospital stay, and intrasellar residual tumor. Results  279 patients (89 pre-MDT vs. 190 post-MDT) were assessed (age 54 ± 17 years, 48% female). Nonfunctioning adenomas were most common (54%). In the post-MDT era, more clinically functioning tumors (42 vs. 28%, p  = 0.03) were treated. Transient DI and SIADH occurred less often post-MDT (20 vs. 36%, p  < 0.01 and 18 vs. 39%, p  < 0.01), as well as new hypothyroidism (5 vs. 15, p  < 0.01). Hospital stay was shorter post-MDT (5[3] vs. 7[5] days, p  < 0.001) and intrasellar residuals were less common (8 vs. 35%, p  < 0.001). Complications were more frequent pre-MDT independent of tumor size, hormone status, and surgical technique (odds ratio [OR] = 2.14 [1.05–4.32], p  = 0.04). Conclusion  Outcomes of pituitary surgery improved after the introduction of an MDT. Pituitary MDTs may benefit both patients and the health system by improving quality of care and reducing hospital stays. [ABSTRACT FROM AUTHOR]

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal "microbiotypes" or "states": the first is Corynebacterium -dominated, the second is Staphylococcus -dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella , and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus , suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future. [ABSTRACT FROM AUTHOR]

Introduction Identifying the internal carotid artery (ICA) when managing petroclival and infratemporal fossa pathology is essential for the skull base surgeon. The vidian nerve and eustachian tube (ET) cartilage come together at the foramen lacerum, the vidian--eustachian junction (VEJ). The ICA position, relative to the VEJ is described. Methods Endoscopic dissection of adult fresh-frozen cadaver ICAs and a case series of patients with petroclival pathology were performed. The relationship of the VEJ to the ICA horizontal segment, vertical segment, and second genu was assessed. The distance of the ICA second genu to VEJ was determined in coronal, axial, and sagittal planes. The length of the vidian nerve and ET was measured from the pterygopalatine fossa (PPF) and nasopharyngeal orifice to the VEJ. Results In this study, 10 cadaver dissections (82.3 ± 6.7 years, 40% female) were performed. The horizontal petrous ICA was at or behind VEJ in 100%, above VEJ in 100%, and lateral to VEJ in80%. The vertical paraclival segment was ator behindVEJ in 100%, above in 100%, and medial in 100%. The second genu was at or behind VEJ in 100% (3.3 ± 2.4 mm), at or above in 100%(2.5 ± 1.6mm), andmedial in100%(3.4 ± 2.0mm). The VEJwas successfully used to locate the ICA in nine consecutive patients (53.3 ± 13.6 years, 55.6% female) where pathology was also present. The VEJ was 15.0 ± 6.0 mm from the ET and 17.4 ± 4.1 mm from the PPF. Conclusion The VEJ is an excellent landmark as it defines both superior and posterior limits when isolating the ICA in skull base surgery. [ABSTRACT FROM AUTHOR]

Unmanned aerial systems (UASs), frequently referred to as 'drones', have become more common and affordable and are a promising tool for collecting data on free-ranging wild animals. We used a Phantom-2 UAS equipped with a gimbal-mounted camera to estimate position, velocity and acceleration of a subject on the ground moving through a grid of GPS surveyed ground control points (area ∼1200 m2). We validated the accuracy of the system against a dual frequency survey grade GPS system attached to the subject. When compared with GPS survey data, the estimations of position, velocity and acceleration had a root mean square error of 0.13 m, 0.11 m s-1 and 2.31 m s-2, respectively. The system can be used to collect locomotion and localisation data on multiple free-ranging animals simultaneously. It does not require specialist skills to operate, is easily transported to field locations, and is rapidly and easily deployed. It is therefore a useful addition to the range of methods available for field data collection on free-ranging animal locomotion. [ABSTRACT FROM AUTHOR]

Route taken and distance travelled are important parameters for studies of animal locomotion. They are often measured using a collar equipped with GPS. Collar weight restrictions limit battery size, which leads to a compromise between collar operating life and GPS fix rate. In studies that rely on linear interpolation between intermittent GPS fixes, path tortuosity will often lead to inaccurate path and distance travelled estimates. Here, we investigate whether GPS-corrected dead reckoning can improve the accuracy of localization and distance travelled estimates while maximizing collar operating life. Custom-built tracking collars were deployed on nine freely exercising domestic dogs to collect high fix rate GPS data. Simulations were carried out to measure the extent to which combining accelerometer-based speed and magnetometer heading estimates (dead reckoning) with low fix rate GPS drift correction could improve the accuracy of path and distance travelled estimates. In our study, median 2-dimensional root-mean-squared (2D- RMS) position error was between 158 and 463 m (median path length 16.43 km) and distance travelled was underestimated by between 30% and 64% when a GPS position fix was taken every 5 min. Dead reckoning with GPS drift correction (1 GPS fix every 5 min) reduced 2D- RMS position error to between 15 and 38 m and distance travelled to between an underestimation of 2% and an overestimation of 5%. Achieving this accuracy from GPS alone would require approximately 12 fixes every minute and result in a battery life of approximately 11 days; dead reckoning reduces the number of fixes required, enabling a collar life of approximately 10 months. Our results are generally applicable to GPS-based tracking studies of quadrupedal animals and could be applied to studies of energetics, behavioral ecology, and locomotion. This low-cost approach overcomes the limitation of low fix rate GPS and enables the long-term deployment of lightweight GPS collars. [ABSTRACT FROM AUTHOR]

Background The return of olfaction and of sinonasal function are important end points after pituitary surgery. Opinions differ on the impact of surgery because techniques vary greatly. A modified preservation of the so-called olfactory strip is described that utilizes a small nasoseptal flap and wide exposure. Methods A cohort of patients undergoing pituitary surgery and endoscopic sinonasal tumor surgery were assessed. Patient-reported outcomes (Sino-Nasal Outcome Test [SNOT22] and Nasal Symptom Score [NSS]) were recorded. A global score of sinonasal function and the impact on smell and taste were obtained. Objective smell discrimination testing was performed in the pituitary group with the Smell Identification Test. Outcomes were assessed at baseline and at 6 months. Results Ninety-eight patients, n 1/4 40 pituitary (50.95 ± 15.31 years; 47.5% female) and n = 58 tumor (52.35 ± 18.51 years; 52.5% female) were assessed. For pituitary patients, NSSs were not significantly different pre- and postsurgery (2.75 ± 3.40 versus 3.05 ± 3.03; p = 0.53). SNOT22 scores improved postsurgery (1.02 ± 0.80 versus 0.83 ± 0.70; p = 0.046). Objective smell discrimination scores between baseline and 6 months were similar (31.63 ± 3.49 versus 31.35 ± 4.61; p = 0.68). No difference in change of olfaction was seen compared with controls (Kendall tau-b p = 0.46). Conclusions Preservation of the olfactory strip can provide a low morbidity approach without adversely affecting olfaction and maintaining reconstruction options. [ABSTRACT FROM AUTHOR]

Objective The nasoseptal flap (NSF) provides vascularized tissue for repair of skull base defects of various etiologies. However, the NSF repair after skull base resection for anterior cranial base malignancies may demonstrate radiologic findings confusing for recurrent or residual disease on postoperative surveillance imaging. The objective of the current study was to review neuroradiologic misinterpretations of NSF reconstruction following anterior cranial base malignancies. Methods A multicenter review of patients reconstructed with the NSF after endoscopic resection of anterior cranial base malignancies from 2008 to 2013 was performed. Data were collected regarding etiology, surgical technique, locoregional control, and postoperative radiologic assessments. Only patients with at least one postoperative surveillance scan with inaccurate assessment of residual or recurrent malignancy were included in the study. Results Over 5 years, 13 patients were identified who had erroneous reporting of malignancy due to NSF reconstruction. On average, two neuroradiologists interpreted the NSF as persistent or recurrent malignancy over this time period (range: 1-7). The key findings suspicious for recurrence were enhancement and soft tissue thickening of the NSF. These findings were present in at least one postoperative scan in all patients. Conclusion Neuroradiologists and rhinologists performing surveillance on patients with a history of skull base malignancy with NSF reconstruction should maintain collaborative efforts to accurately interpret radiologic findings of the NSF during postoperative imaging. [ABSTRACT FROM AUTHOR]

Objective To examine the risk of postoperative meningitis following expanded endoscopic endonasal skull base (EESB) surgery. Setting A systematic analysis of publications identified through searches of the electronic databases from Embase (1980-July 17, 2012), Medline (1950-July 17, 2012), and references of review articles. Main Outcome Measures Incidence of meningitis following EESB surgery. Results A total of 2,444 manuscripts were selected initially, and full-text analysis produced 67 studies with extractable data. Fifty-two contained data regarding the frequency of postoperative meningitis. The overall risk of postoperative meningitis following EESB surgery was 1.8% (36 of 2,005). For those reporting a cerebrospinal fluid (CSF) leak, meningitis occurred in 13.0% (35 of 269). For those not reporting a CSF leak, meningitis occurred in 0.1% (1 of 1,736). The odds ratio for the development of meningitis in the presence of a postoperative CSF leak was 91.99 (95% confidence interval, 11.72-721.88; p < 0.01). There was no difference in reported incidence of meningitis or CSF leak between anterior and posterior cranial fossa surgery. There was one reported case of meningitis-related mortality following EESB surgery. Conclusion The evidence in skull base surgery is limited. This study demonstrates a low incidence of meningitis (1.8%) following EESB procedures. The incidence of meningitis from EESB surgery without an associated CSF leak is uncommon. [ABSTRACT FROM AUTHOR]

Objective To investigate the relevance of an endoscopic transnasal approach to the surgical treatment of paraophthalmic aneurysms. Setting Binasal endoscopic transplanum surgery was performed. Participants Seven cadaver heads were studied. Main Outcome Measures (1) Dimensions of the endonasal corridor, including the operative field depth, lateral limits, and the transplanum craniotomy. (2) The degree of vascular exposure. (3) Surgical maneuverability and access for clip placements. Results The mean operative depth was 90 ± 4 mm. The lateral corridors were limited proximally by the alar rim openings (29 ± 4 mm) and distally by the distance between the opticocarotid recesses (19 ± 2 mm). The mean posteroanterior distance and width of the transplanum craniotomy were 19 ± 2 mm and 17 ± 3 mm, respectively. Vascular exposure was achieved in 100% of cases for the clinoidal internal carotid artery (ICA), ophthalmic artery, superior hypophyseal artery, and the proximal ophthalmic ICA. Surgical access and clip placement was achieved in 97.6% of cases for vessels located anterior to the pituitary stalk (odds ratio [OR] 73.8; 95% confidence interval [CI] 7.66 to 710.8; p = 0.00). Conclusion The endoscopic transnasal approach provides excellent visualization of the paraclinoid region vasculature and offers potential surgical alternative for paraclinoid aneurysms. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes mellitus (DM) are susceptible to invasive fungal rhinosinusitis (IFRS). The mortality rate of IFRS varies greatly among the patients with DM., Objective: To identify the prognostic factors for the overall survival of patients with DM and IFRS., Methods: A retrospective study was conducted in four tertiary hospitals in Thailand, Malaysia and Myanmar. Patients diagnosed with IFRS and DM from 2008 to 2019 were identified. The outcome was the overall survival. Variables analyzed for risk factors were age, HbA1C level, ketoacidosis, white blood cell count, hyperglycemia, duration of DM, current use of diabetic medications, serum creatinine level, and the extensions of IFRS to the orbit, the cavernous sinus and intracranial cavity., Results: Sixty-five diabetic patients with IFRS (age 57.9 ± 13.4 years, male 60%) were identified. The mortality rate was 21.5%. The extensions of IFRS to the cavernous sinus (hazard ratio 5.1, 95% CI [1.4-18.2], p = 0.01) and intracranial cavity (hazard ratio 3.4, 95% CI [1.1-11.3, p = 0.05) predicted mortality. Current use of diabetic medications decreased the mortality risk (hazard ratio 0.2, 95% CI [0.1-0.9], p = 0.03). The 6-month overall survival of the patients with and without the cavernous sinus extension were 51.4% and 83.6%, (p = 0.001), with and without intracranial extension 53.3% and 88.9%, (p = 0.001), and with and without current diabetic medications 82.3% and 57.5%, respectively (p = 0.045)., Conclusions: The extensions of IFRS to the cavernous sinus and intracranial cavity increased the risk of death in patients with DM. Survival was primarily related to current use of diabetic medications.

Objectives  Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods  Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results  Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2  = -0.417, p  = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p  = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p  = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p  = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p  = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2  = -0.682, p  < 0.001, MIDAS: R 2  = -0.880, p  < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p  = 0.0030). Conclusion  Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion., Competing Interests: Conflict of Interest R. J. H. is consultant with Medtronic, Stryker, Novartis, Meda, and NeilMed pharmaceuticals. Research grant funding received from Glaxo-Smith-Kline and Stallergenes. He has been on the speakers' bureau for Glaxo-Smith-Kline, Meda Pharmaceuticals, and Seqirus. A. M. has received speaker fees and research grants from Novartis Pharmaceuticals, Ipsen, and Pfizer. B. P. J. has received speaker fees from Integra LifeSciences Corporation. L. H. K. is on the speakers' bureau for Care Pharmaceuticals and Mylan Pharmaceuticals. R. S. is a consultant for Medtronic and is in the speaker bureau for Meda Pharmaceuticals. All other authors have no financial disclosures or conflicts of interest., (Thieme. All rights reserved.)

Objective: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease. The objectives of the study were to determine remission and recurrence rates after TSS for Cushing's disease, identify factors that predict these outcomes, and define the threshold for postoperative morning serum cortisol (MSeC) that most accurately predicts sustained remission., Methods: Records were retrospectively reviewed for consecutive adults undergoing TSS for Cushing's disease at a tertiary centre (1990-2019). Remission was defined as MSeC <138 nmol/L by 6 weeks postoperatively. Recurrence was defined as elevated 24-h urine free cortisol, lack of suppression after dexamethasone or elevated midnight salivary cortisol., Results: In this study, 42 patients (age 47 ± 13 years, 83% female) were assessed with 55 ± 56 months of follow-up. Remission occurred after 77% of primary ( n  = 30) and 42% of revision operations ( n  = 12). After primary surgery, remission was associated with lower MSeC nadir (26 ± 36 nmol/L vs 347 ± 220 nmol/L, P   < 0.01) and lower adrenocorticotropin nadir (2 ± 3 pmol/L vs 6 ± 3 pmol/L, P  = 0.01). Sustained remission 5 years after surgery was predicted by MSeC <92 nmol/L within 2 weeks postoperatively (sensitivity 100% and specificity 100%). After revision surgery, remission was predicted by lower MSeC nadir (70 ± 45 nmol/L vs 408 ± 305 nmol/L, P  = 0.03), smaller tumour diameter (3 ± 2 mm vs 15 ± 13 mm, P  = 0.05) and absence of cavernous sinus invasion (0% vs 71%, P  = 0.03). Recurrence after primary and revision surgery occurred in 17% and 20% of patients respectively., Conclusions: Lower postoperative MSeC nadir strongly predicted remission after both primary and revision surgery. Following primary surgery, an MSeC <92 nmol/L within 2 weeks predicted sustained remission at 5 years. MSeC nadir was the most important prognostic marker following TSS for Cushing's disease., Competing Interests: Richard J Harvey is consultant with Medtronic, Stryker, Novartis, Meda, and NeilMed pharmaceuticals. Research grant funding received from Glaxo-Smith-Kline and Stallergenes. He has been on the speakers’ bureau for Glaxo-Smith-Kline, Meda Pharmaceuticals and Seqirus. Ann McCormack has received speaker honorarium for IPSEN, Pfizer and Novartis. Benjamin P Jonker has received speaker fees from Integra LifeSciences Corporation. All other authors have no financial disclosures or conflicts of interest., (© The authors.)

Background: Temperate grass (eg, ryegrass) pollen is a major driver of seasonal allergic rhinitis (SAR) and asthma risks, including thunderstorm asthma. Data for the effectiveness of temperate grass pollen allergen immunotherapy (AIT) in SAR patients from the southern hemisphere, who are frequently polysensitized to subtropical grass pollens, are limited. The 300 IR 5-grass pollen sublingual immunotherapy tablet (300 IR 5-grass SLIT) is known to be effective in polysensitized SAR patients with primary allergy to temperate grasses, however, the influence of polysensitization to subtropical grass pollen on treatment responses has yet to be specifically addressed. Key aims of this study were to measure patient treatment satisfaction during 300 IR 5-grass SLIT treatment and evaluate how polysensitization to subtropical grass pollens affects treatment responses., Methods: A prospective observational study was conducted in 63 patients (aged ≥5 years) in several temperate regions of Australia prescribed 300 IR 5-grass SLIT for SAR over 3 consecutive grass pollen seasons. Ambient levels of pollen were measured at representative sites. Patient treatment satisfaction was assessed using a QUARTIS questionnaire. Rhinoconjunctivitis Total Symptom Score (RTSS) and a Hodges-Lehmann Estimator analysis was performed to evaluate if polysensitization to subtropical grass pollen affected SAR symptom intensity changes during SLIT., Results: A diagnosis of ryegrass pollen allergy was nearly universal. There were 74.6% (47/63) polysensitized to subtropical and temperate grass pollens. There were 23.8% (15/63) monosensitized to temperate grass pollens. From the first pollen season, statistically significant improvements occurred in SAR symptoms compared with baseline in both monosensitized and polysensitized patients, particularly in those polysensitized (P = 0.0297). Improvements in SAR symptoms were sustained and similar in both groups in the second and third pollen seasons, reaching 70-85% improvement (P < 0.01). Polysensitized patients from both northerly and southerly temperate regions in Australia showed similar improvements. Grass pollen counts in both regions were consistently highest during springtime., Conclusions: 300 IR 5-grass SLIT is effective in a real-life setting in SAR patients in the southern hemisphere with primary allergy to temperate grass pollen and predominantly springtime grass pollen exposures. Importantly, SLIT treatment effectiveness was irrespective of the patient's polysensitization status to subtropical grass pollens., Competing Interests: SvN, MBB, PKB, GF, AL, EP, JSR, MFS, FT, HCW, HZ, EN and CHK, have no conflict of interest to declare. JS declares membership of Advisory Boards for Takeda and CSL. RJH declares consultancies/Advisory Board membership of Medtronic, Novartis, GSK and Meda Pharmaceuticals. Research grant funding received from Glaxo-Smith-Kline. Speakers' bureau for Glaxo-Smith-Kline, AstraZeneca, Meda Pharmaceuticals and Seqirus., (© 2022 The Author(s).)

Kimura's disease is a rare, benign, chronic inflammatory disorder characterised by its eosinophilic infiltrate. Patients often present with one or more progressively enlarging subcutaneous lymph nodes in the head and neck region or enlarging salivary glands. We describe the case of a 26-year-old man presenting with severe peripheral eosinophilia and upper airway inflammatory symptoms, who later developed cervical lymphadenopathy and formally diagnosed with Kimura's disease. Based on our English-language MEDLINE literature search, to our knowledge this is the first case report describing treatment of Kimura's disease with mepolizumab., Competing Interests: Competing interests: RJH is a consultant with Medtronic, Olympus and NeilMed pharmaceuticals. He has also been on the speakers’ bureau for Glaxo-Smith-Kline, Seqiris and Astra-Zeneca. JH is supported by an Australian Government Research Training Program (RTP) Scholarship. All other authors have no financial disclosures or conflicts of interest., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Since fungi were postulated as a potential cause of CRS in the late 1990s, there has been increasing controversy about the use of both topical and systemic antifungal agents in its management. Although interaction between the immune system and fungus has been demonstrated in CRS, this does not necessarily imply that fungi are the cause of CRS or that antifungals will be effective its management., Objectives: To assess the effectiveness of topical or systemic antifungal therapy in the treatment of CRS., Search Methods: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 March 2011., Selection Criteria: All randomised, placebo-controlled trials considering the use of topical or systemic antifungal therapy in the treatment of CRS and allergic fungal sinusitis (AFS). CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria., Data Collection and Analysis: We reviewed the titles and abstracts of all studies obtained from the searches and selected trials that met the eligibility criteria. We extracted data using a pre-determined data extraction form. There was significant heterogeneity of outcome data reporting with reports containing both parametric and non-parametric representations of data for the same outcomes. Means and standard deviations for change data were unavailable for a number of trials. Due to the limited reported data, we contacted authors and used original data for data analysis., Main Results: Six studies were included (380 participants). Five studies investigated topical antifungals and one study investigated systemic antifungals. The risk of bias in all included studies was low, with all trials being double-blinded and randomised. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo for any outcome. Symptom scores in fact statistically favoured the placebo group. Adverse event reporting was statistically significantly higher in the antifungal group., Authors' Conclusions: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.

Background: Alzheimer's disease is the most common cause of dementia in older people. One approach to symptomatic treatment of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by blocking the action of the enzyme responsible for the breakdown of the neurotransmitter acetylcholine. This can be done by a group of drugs known as cholinesterase inhibitors. Donepezil is a cholinesterase inhibitor.This review is an updated version of a review first published in 1998., Objectives: To assess the clinical efficacy and safety of donepezil in people with mild, moderate or severe dementia due to Alzheimer's disease; to compare the efficacy and safety of different doses of donepezil; and to assess the effect of donepezil on healthcare resource use and costs., Search Methods: We searched Cochrane Dementia and Cognitive Improvement's Specialized Register, MEDLINE, Embase, PsycINFO and a number of other sources on 20 May 2017 to ensure that the search was as comprehensive and up-to-date as possible. In addition, we contacted members of the Donepezil Study Group and Eisai Inc., Selection Criteria: We included all double-blind, randomised controlled trials in which treatment with donepezil was administered to people with mild, moderate or severe dementia due to Alzheimer's disease for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two different doses of donepezil were compared., Data Collection and Analysis: One reviewer (JSB) extracted data on cognitive function, activities of daily living, behavioural symptoms, global clinical state, quality of life, adverse events, deaths and healthcare resource costs. Where appropriate and possible, we estimated pooled treatment effects. We used GRADE methods to assess the quality of the evidence for each outcome., Main Results: Thirty studies involving 8257 participants met the inclusion criteria of the review, of which 28 studies reported results in sufficient detail for the meta-analyses. Most studies were of six months' duration or less. Only one small trial lasted 52 weeks. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day. Two studies tested a slow-release oral formulation that delivered 23 mg/day. Participants in 21 studies had mild to moderate disease, in five studies moderate to severe, and in four severe disease. Seventeen studies were industry funded or sponsored, four studies were funded independently of industry and for nine studies there was no information on source of funding.Our main analysis compared the safety and efficacy of donepezil 10 mg/day with placebo at 24 to 26 weeks of treatment. Thirteen studies contributed data from 3396 participants to this analysis. Eleven of these studies were multicentre studies. Seven studies recruited patients with mild to moderate Alzheimer's disease, two with moderate to severe, and four with severe Alzheimer's disease, with a mean age of about 75 years. Almost all evidence was of moderate quality, downgraded due to study limitations.After 26 weeks of treatment, donepezil compared with placebo was associated with better outcomes for cognitive function measured with the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog, range 0 to 70) (mean difference (MD) -2.67, 95% confidence interval (CI) -3.31 to -2.02, 1130 participants, 5 studies), the Mini-Mental State Examination (MMSE) score (MD 1.05, 95% CI 0.73 to 1.37, 1757 participants, 7 studies) and the Severe Impairment Battery (SIB, range 0 to 100) (MD 5.92, 95% CI 4.53 to 7.31, 1348 participants, 5 studies). Donepezil was also associated with better function measured with the Alzheimer's Disease Cooperative Study activities of daily living score for severe Alzheimer's disease (ADCS-ADL-sev) (MD 1.03, 95% CI 0.21 to 1.85, 733 participants, 3 studies). A higher proportion of participants treated with donepezil experienced improvement on the clinician-rated global impression of change scale (odds ratio (OR) 1.92, 95% CI 1.54 to 2.39, 1674 participants, 6 studies). There was no difference between donepezil and placebo for behavioural symptoms measured by the Neuropsychiatric Inventory (NPI) (MD -1.62, 95% CI -3.43 to 0.19, 1035 participants, 4 studies) or by the Behavioural Pathology in Alzheimer's Disease (BEHAVE-AD) scale (MD 0.4, 95% CI -1.28 to 2.08, 194 participants, 1 study). There was also no difference between donepezil and placebo for Quality of Life (QoL) (MD -2.79, 95% CI -8.15 to 2.56, 815 participants, 2 studies).Participants receiving donepezil were more likely to withdraw from the studies before the end of treatment (24% versus 20%, OR 1.25, 95% CI 1.05 to 1.50, 2846 participants, 12 studies) or to experience an adverse event during the studies (72% vs 65%, OR 1.59, 95% 1.31 to 1.95, 2500 participants, 10 studies).There was no evidence of a difference between donepezil and placebo for patient total healthcare resource utilisation.Three studies compared donepezil 10 mg/day to donepezil 5 mg/day over 26 weeks. The 5 mg dose was associated with slightly worse cognitive function on the ADAS-Cog, but not on the MMSE or SIB, with slightly better QoL and with fewer adverse events and withdrawals from treatment. Two studies compared donepezil 10 mg/day to donepezil 23 mg/day. There were no differences on efficacy outcomes, but fewer participants on 10 mg/day experienced adverse events or withdrew from treatment., Authors' Conclusions: There is moderate-quality evidence that people with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12 or 24 weeks with donepezil experience small benefits in cognitive function, activities of daily living and clinician-rated global clinical state. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total healthcare resource costs. Benefits on 23 mg/day were no greater than on 10 mg/day, and benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose, but the rates of withdrawal and of adverse events before end of treatment were higher the higher the dose.

Background The return of olfaction and of sinonasal function are important end points after pituitary surgery. Opinions differ on the impact of surgery because techniques vary greatly. A modified preservation of the so-called olfactory strip is described that utilizes a small nasoseptal flap and wide exposure. Methods A cohort of patients undergoing pituitary surgery and endoscopic sinonasal tumor surgery were assessed. Patient-reported outcomes (Sino-Nasal Outcome Test [SNOT22] and Nasal Symptom Score [NSS]) were recorded. A global score of sinonasal function and the impact on smell and taste were obtained. Objective smell discrimination testing was performed in the pituitary group with the Smell Identification Test. Outcomes were assessed at baseline and at 6 months. Results Ninety-eight patients, n = 40 pituitary (50.95 ± 15.31 years; 47.5% female) and n = 58 tumor (52.35 ± 18.51 years; 52.5% female) were assessed. For pituitary patients, NSSs were not significantly different pre- and postsurgery (2.75 ± 3.40 versus 3.05 ± 3.03; p = 0.53). SNOT22 scores improved postsurgery (1.02 ± 0.80 versus 0.83 ± 0.70; p = 0.046). Objective smell discrimination scores between baseline and 6 months were similar (31.63 ± 3.49 versus 31.35 ± 4.61; p = 0.68). No difference in change of olfaction was seen compared with controls (Kendall tau-b p = 0.46). Conclusions Preservation of the olfactory strip can provide a low morbidity approach without adversely affecting olfaction and maintaining reconstruction options.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents inflammatory changes throughout the nose and sinuses from a group of disorders which all lead to swelling and overgrowth of the nasal mucosa. Topical corticosteroids have been the most widely used treatment, with each clinician using different regimes, at different doses, in different settings and with or without sinus surgery. CRSwNP requires ongoing medical management to prevent recurrence., Objectives: To assess the effects of topical corticosteroids on CRSwNP and to analyse various subgroups, including patients who had sinus surgery immediately prior to the delivery of the corticosteroids, surgery any time prior to the topical corticosteroids or patients who had never had previous surgery. Also to assess the most effective dose and delivery methods for topical corticosteroids., Search Methods: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 April 2012., Selection Criteria: Randomised controlled trials studying topical corticosteroids for patients with CRSwNP., Data Collection and Analysis: At least two authors reviewed the search results and selected trials meeting the eligibility criteria, obtaining full texts and contacting authors. We documented our justification for the exclusion of studies. At least two authors extracted data using a pre-determined, standardised data form., Main Results: Forty studies (3624 patients) met the inclusion criteria. The trials were at low (21 trials), medium (13 trials) and high (six trials) risk of bias. The primary outcomes were sino-nasal symptoms, polyp size and polyp recurrence after surgery. When compared to placebo, topical corticosteroids improved overall symptom scores (standardised mean difference (SMD) -0.46; 95% confidence interval (CI) -0.65 to -0.27, P < 0.00001; seven trials, n = 445) and had a higher proportion of patients whose symptoms improved (responders) (risk ratio (RR) 1.71; 95% CI 1.29 to 2.26, P = 0.0002; four trials, n = 234). Topical corticosteroids also decreased the polyp score (SMD -0.73; 95% CI -1.00 to -0.46, P < 0.00001; three trials, n = 237) and had a greater proportion of patients with a reduction in polyp size (responders) (RR 2.09; 95% CI 1.65 to 2.64, P < 0.00001; eight trials, n = 785) when compared to placebo. Topical corticosteroids also prevented polyp recurrence after surgery (RR 0.59; 95% CI 0.45 to 0.79, P = 0.0004; six trials, n = 437). Subgroup analyses by sinus surgery status revealed a greater benefit in reduction of polyp score when topical steroid was administered any time after sinus surgery (SMD -1.19; 95% CI -1.54 to -0.83) compared to patients who had never had surgery (SMD -0.13; 95% CI -0.53 to 0.28, P < 0.00001). There was no difference between groups in terms of adverse events., Authors' Conclusions: Topical corticosteroids are a beneficial treatment for CRSwNP and the adverse effects are minor, with benefits outweighing the risks. They improve symptoms, reduce polyp size and prevent polyp recurrence after surgery. Patients having sinus surgery may have a greater response to topical corticosteroids but further research is required.

Background: Topical corticosteroid is used as part of a comprehensive medical treatment for chronic rhinosinusitis (CRS) without polyps. Nevertheless, there is insufficient evidence to show a clear overall benefit. Trials studying the efficacy of topical corticosteroid use various delivery methods in patients who have or have not had sinus surgery, which directly impacts on topical delivery and distribution., Objectives: To assess the effects of topical steroid in patients with CRS without nasal polyps and perform a meta-analysis of symptom improvement data, including subgroup analysis by sinus surgery status and topical delivery methods., Search Strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 9 July 2010., Selection Criteria: All randomised trials in which a topically administered corticosteroid was compared with either a placebo, no treatment or alternative topically administered corticosteroid for the treatment of CRS without polyps in patients of any age., Data Collection and Analysis: Two authors reviewed the search results and selected trials meeting the eligibility criteria, obtaining full texts and contacting authors where necessary. We documented our justification for the exclusion of studies. Two authors extracted data using a pre-determined standardised data form., Main Results: Ten studies (590 patients) met the inclusion criteria. The trials were of low (six trials) and medium (four trials) risk of bias. The primary outcome was sino-nasal symptoms. When compared to placebo, topical steroid improved symptom scores (standardised mean difference -0.37; 95% confidence interval (CI) -0.60 to -0.13, P = 0.002; five trials, n = 286) and had a greater proportion of responders (risk ratio 1.69; 95% CI 1.21 to 2.37, P = 0.002; four trials, n = 263). With a limited number of studies, the subgroup analyses of patients who had received sinus surgery versus those who had not was not significant (P = 0.35). Subgroup analyses by topical delivery method revealed more benefit when steroid was administered directly to the sinuses than with simple nasal delivery (P = 0.04). There were no differences between groups for quality of life and adverse events., Authors' Conclusions: Topical steroid is a beneficial treatment for CRS without polyps and the adverse effects are minor. It may be included in a comprehensive treatment of CRS without polyps. Direct delivery of steroid to the sinuses may bring more beneficial effect. Further studies comparing different topical drug delivery methods to the sinuses, with appropriate treatment duration (longer than 12 weeks), are required.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and sinuses. Since fungi were postulated as a potential cause of CRS in the late 1990s, there has been increasing controversy about the use of both topical and systemic antifungal agents in its management. Although interaction between the immune system and fungus has been demonstrated in CRS, this does not necessarily imply that fungi are the cause of CRS or that antifungals will be effective its management., Objectives: To assess the effectiveness of topical or systemic antifungal therapy in the treatment of CRS., Search Strategy: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 8 March 2011., Selection Criteria: All randomised, placebo-controlled trials considering the use of topical or systemic antifungal therapy in the treatment of CRS and allergic fungal sinusitis (AFS). CRS was defined using either the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria., Data Collection and Analysis: We reviewed the titles and abstracts of all studies obtained from the searches and selected trials that met the eligibility criteria. We extracted data using a pre-determined data extraction form. There was significant heterogeneity of outcome data reporting with reports containing both parametric and non-parametric representations of data for the same outcomes. Means and standard deviations for change data were unavailable for a number of trials. Due to the limited reported data, we contacted authors and used original data for data analysis., Main Results: Six studies were included (380 participants). Five studies investigated topical antifungals and one study investigated systemic antifungals. The risk of bias in all included studies was low, with all trials being double-blinded and randomised. Pooled meta-analysis showed no statistically significant benefit of topical or systemic antifungals over placebo for any outcome. Symptom scores in fact statistically favoured the placebo group. Adverse event reporting was statistically significantly higher in the antifungal group., Authors' Conclusions: On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.