Archetypal clustering reveals physiological mechanisms linking milk yield and fertility in dairy cattle.

Fertility in dairy cattle has declined as an unintended consequence of single-trait selection for high milk yield. The unfavorable genetic correlation between milk yield and fertility is now well documented; however, the underlying physiological mechanisms are still uncertain. To understand the relationship between these traits, we developed a method that clusters variants with similar patterns of effects and, after the integration of gene expression data, identifies the genes through which they are likely to act. Biological processes that are enriched in the genes of each cluster were then identified. We identified several clusters with unique patterns of effects. One of the clusters included variants associated with increased milk yield and decreased fertility, where the "archetypal" variant (i.e., the one with the largest effect) was associated with the GC gene, whereas others were associated with TRIM32, LRRK2, and U6-associated snRNA. These genes have been linked to transcription and alternative splicing, suggesting that these processes are likely contributors to the unfavorable relationship between the 2 traits. Another cluster, with archetypal variant near DGAT1 and including variants associated with CDH2, BTRC, SFRP2, ZFHX3, and SLITRK5, appeared to affect milk yield but have little effect on fertility. These genes have been linked to insulin, adipose tissue, and energy metabolism. A third cluster with archetypal variant near ZNF613 and including variants associated with ROBO1, EFNA5, PALLD, GPC6, and PTPRT were associated with fertility but not milk yield. These genes have been linked to GnRH neuronal migration, embryonic development, or ovarian function. The use of archetypal clustering to group variants with similar patterns of effects may assist in identifying the biological processes underlying correlated traits. The method is hypothesis generating and requires experimental confirmation. However, we have uncovered several novel mechanisms potentially affecting milk production and fertility such as GnRH neuronal migration. We anticipate our method to be a starting point for experimental research into novel pathways, which have been previously unexplored within the context of dairy production.

Validating the female fertility estimated breeding value in Australian commercial dairy herds.

We conducted a retrospective cohort study to validate the efficacy of the Australian multitrait fertility estimated breeding value (EBV). We did this by determining its associations with phenotypic measures of reproductive performance (i.e., submission rate, first service conception rate, and early calving). Our secondary aim was to report the associations between these reproductive outcomes and management and climate-related factors hypothesized to affect fertility. Our study population included 38 pasture-based dairy herds from the northern Victorian irrigation region in Australia. We collected records for 86,974 cows with 219,156 lactations and 438,578 mating events from the date on which managers started herd recording until December 2016, comprising both fertility-related data such as insemination records, calving dates, and pregnancy test results, and systems-related data such as production, herd size, and calving pattern. We also collected hourly data from 2004 to 2017 from the closest available weather station to account for climate-related factors (i.e., temperature humidity index; THI). Multilevel Cox proportional hazard models were used to analyze time-to-event outcomes (days to first service, days to cow calving following the planned herd calving start date), and multilevel logistic regression models for binomial outcomes (conception to first service) in the Holstein-Friesian and Jersey breeds. A 1-unit increase in daughter fertility EBV was associated with a 5.4 and 8.2% increase in the daily hazard of calving in the Holstein-Friesian and Jersey breeds respectively. These are relative increases (i.e., a Holstein-Friesian herd with a 60% 6-wk in-calf rate would see an improvement to 63.2% with a 1-unit increase in herd fertility EBV). Similar results were obtained for submission and conception rate. Associations between 120-d milk yield and reproductive outcome were complicated by interactions with 120-d protein percentage and calving age, depending on the breed and outcome. In general, we found that the reproductive performance of high milk-yielding animals deteriorated faster with age than low milk-yielding animals, and high protein percentage exacerbated the differences between low and high milk-yielding animals. Climate-related factors were also associated with fertility, with a 1-unit increase in maximum THI decreasing first service conception rate by 1.2% for Holstein-Friesians but having no statistically significant association in the Jersey breed. However, THI had a negative association in both breeds on the daily hazard of calving. Our study validates the efficacy of the daughter fertility EBV for improving herd reproductive performance and identifies significant associations between 120-d milk and protein yields and THI on the fertility of Australian dairy cows.

A systematic review and meta-analysis of the role of doxycycline in chronic rhinosinusitis.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis. METHOD: This was a systematic review using Ovid Medline, Cinahl, Scopus and Cochrane and was limited to meta-analyses, systematic reviews and randomised, clinical trials. A combination of the following search terms was used: 'sinusitis', 'nasal polyps', 'doxycycline' and 'tetracycline'. Raw means and standard deviations were extracted from the included studies. The meta-analysis was performed using mean differences of pre- versus post-doxycycline treatment. RESULTS: A total of 279 studies were screened, of which 5 studies met the criteria (all randomised, controlled trials published between 2010 and 2021). The interventions, endpoints and measured outcomes varied across all studies. Meta-analysis performed on pre- versus post-doxycycline treatment for Sino-Nasal Outcome Test-22, nasal polyp scores and symptom scores did not yield statistically significant results. CONCLUSION: This review identified a small number of high-quality studies on the use of doxycycline in chronic rhinosinusitis. There does not seem to be convincing evidence for the routine use of doxycycline in patients with chronic rhinosinusitis. Further research may try to identify certain phenotypes of chronic rhinosinusitis that may better respond to doxycycline.

Herd manager attitudes and intentions regarding the selection of high-fertility EBV sires in Australia.

Reproductive performance in dairy cattle has declined over the last 50 years as an unintended consequence of selection for high milk yield. Since the early 2000s, dairy geneticists have released successive versions of fertility estimated breeding values (EBV) to assist in reversing this trend. At the herd level, fertility EBV can help managers accelerate improvements in reproductive performance by acting as a second selection criteria when used in tandem with a breeding index. However, use of the fertility EBV in sire selection currently varies between herd managers. The aim of this study was to better understand the reasons why herd managers choose or do not choose to select high-fertility EBV sires, using the Theory of Planned Behavior (TPB) as a social research framework. Thirty-five Victorian dairy herd managers were recruited as part of a larger study investigating the daughter fertility Australian Breeding Value and interviewed using a series of questions examining TPB constructs. The interviews were recorded and transcribed using template analysis. A wide range of herd manager types were enrolled into the study, with representation from diverse systems. Out of the 35 herd managers, 27 included fertility in their list of high-priority breeding objectives. A wide variation in results was consistent with previous studies that have demonstrated marked heterogeneity in herd manager attitudes toward bull selection. Herd manager-perceived barriers to selection of sires with high daughter fertility EBV included a lack of high daughter fertility bulls with other desirable traits, a lack of trust in the fertility EBV or in the Australian EBV system, difficulty in interpreting international proofs, information overload, semen prices, low bull reliability, and difficulty in understanding bull catalogs. Not all herd managers found the process problematic, however, particularly if a breeding consultant was employed to select all or most of the sires. Herd manager-perceived barriers for choosing to select daughter fertility as a breeding objective include a lack of awareness of the EBV, a lack of interest in genetics in general, low confidence in the impact of genetic selection for fertility, and a feeling that fertility was not important for their production system. The results of this study suggest that animal geneticists and on-farm service providers need to work together to allow the opportunities arising from appropriate use of fertility EBV to be realized more broadly across the dairy industry.

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Transoral robotic surgery using the Medrobotic Flex® system: the Adelaide experience.

Transoral robotic surgery (TORS) has become an accepted treatment option for a variety of benign and malignant pathologies of the head and neck. The Medrobotics Flex® system is a novel single port platform available as an alternative tool to current multiport robotic technology. We present the Adelaide experience with this system thus far. The Medrobotics Flex® system was introduced in Adelaide in January 2017. Patient demographics, pathology, indication for surgery and complications are prospectively recorded for all cases. The first 20 patients are presented in this case series. 11/20 underwent surgery for malignant disease. Of these nine were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC). Histopathology revealed clear margins of primary tumour excision in 8/9 patients. There were no intraoperative complications. In terms of secondary complications, one patient undergoing tonsillectomy for recurrent tonsillitis experienced a secondary haemorrhage at day 13 following operation and one patient undergoing lateral oropharyngectomy for pT3N2b tonsillar SCC sustained an oro-cervical fistula, which settled with conservative management. We have found the Medrobotic Flex® system to be a safe, reliable tool for managing transoral surgery. The range of pathology managed with this platform, as well as the histologic outcomes presented, demonstrates efficacy in the oropharynx and posterior oral cavity for both benign and malignant disease.

Rapid sperm capture: high-throughput flagellar waveform analysis.

STUDY QUESTION: Can flagellar analyses be scaled up to provide automated tracking of motile sperm, and does knowledge of the flagellar waveform provide new insight not provided by routine head tracking? SUMMARY ANSWER: High-throughput flagellar waveform tracking and analysis enable measurement of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses, which are not possible by tracking the sperm head alone. WHAT IS KNOWN ALREADY: The clinical gold standard for sperm motility analysis comprises a manual analysis by a trained professional, with existing automated sperm diagnostics [computer-aided sperm analysis (CASA)] relying on tracking the sperm head and extrapolating measures. It is not currently possible with either of these approaches to track the sperm flagellar waveform for large numbers of cells in order to unlock the potential wealth of information enclosed within. STUDY DESIGN, SIZE, DURATION: The software tool in this manuscript has been developed to enable high-throughput, repeatable, accurate and verifiable analysis of the sperm flagellar beat. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the software tool [Flagellar Analysis and Sperm Tracking (FAST)] described in this manuscript, we have analysed 176 experimental microscopy videos and have tracked the head and flagellum of 205 progressive cells in diluted semen (DSM), 119 progressive cells in a high-viscosity medium (HVM) and 42 stuck cells in a low-viscosity medium. Unscreened donors were recruited at Birmingham Women's and Children's NHS Foundation Trust after giving informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: We describe fully automated tracking and analysis of flagellar movement for large cell numbers. The analysis is demonstrated on freely motile cells in low- and high-viscosity fluids and validated on published data of tethered cells undergoing pharmacological hyperactivation. Direct analysis of the flagellar beat reveals that the CASA measure 'beat cross frequency' does not measure beat frequency; attempting to fit a straight line between the two measures gives ${\mathrm{R}}^2$ values of 0.042 and 0.00054 for cells in DSM and HVM, respectively. A new measurement, track centroid speed, is validated as an accurate differentiator of progressive motility. Coupled with fluid mechanics codes, waveform data enable extraction of experimentally intractable quantities such as energy dissipation, disturbance of the surrounding medium and viscous stresses. We provide a powerful and accessible research tool, enabling connection of the mechanical activity of the sperm to its motility and effect on its environment. LARGE SCALE DATA: The FAST software package and all documentation can be downloaded from www.flagellarCapture.com. LIMITATIONS, REASONS FOR CAUTION: The FAST software package has only been tested for use with negative phase contrast microscopy. Other imaging modalities, with bright cells on a dark background, have not been tested but may work. FAST is not designed to analyse raw semen; it is specifically for precise analysis of flagellar kinematics, as that is the promising area for computer use. Flagellar capture will always require that cells are at a dilution where their paths do not frequently cross. WIDER IMPLICATIONS OF THE FINDINGS: Combining tracked flagella with mathematical modelling has the potential to reveal new mechanistic insight. By providing the capability as a free-to-use software package, we hope that this ability to accurately quantify the flagellar waveform in large populations of motile cells will enable an abundant array of diagnostic, toxicological and therapeutic possibilities, as well as creating new opportunities for assessing and treating male subfertility. STUDY FUNDING/COMPETING INTEREST(S): M.T.G., G.C., J.C.K-B. and D.J.S. gratefully acknowledge funding from the Engineering and Physical Sciences Research Council, Healthcare Technologies Challenge Award (Rapid Sperm Capture EP/N021096/1). J.C.K-B. is funded by a National Institute of Health Research (NIHR) and Health Education England, Senior Clinical Lectureship Grant: The role of the human sperm in healthy live birth (NIHRDH-HCS SCL-2014-05-001). This article presents independent research funded in part by the NIHR and Health Education England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The data for experimental set (2) were funded through a Wellcome Trust-University of Birmingham Value in People Fellowship Bridging Award (E.H.O.).The authors declare no competing interests.

Reviewing indications for panendoscopy in the investigation of head and neck squamous cell carcinoma.

BACKGROUND: The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer. METHOD: A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.

A systematic review of validated sinus surgery simulators.

BACKGROUND: Simulation provides a safe and effective opportunity to develop surgical skills. A variety of endoscopic sinus surgery (ESS) simulators has been described in the literature. Validation of these simulators allows for effective utilisation in training. OBJECTIVE OF REVIEW: To conduct a systematic review of the published literature to analyse the evidence for validated ESS simulation. SEARCH STRATEGY: Pubmed, Embase, Cochrane and Cinahl were searched from inception of the databases to 11 January 2017. EVALUATION METHOD: Twelve thousand five hundred and sixteen articles were retrieved of which 10 112 were screened following the removal of duplicates. Thirty-eight full-text articles were reviewed after meeting search criteria. Evidence of face, content, construct, discriminant and predictive validity was extracted. RESULTS: Twenty articles were included in the analysis describing 12 ESS simulators. Eleven of these simulators had undergone validation: 3 virtual reality, 7 physical bench models and 1 cadaveric simulator. Seven of the simulators were shown to have face validity, 7 had construct validity and 1 had predictive validity. None of the simulators demonstrated discriminate validity. CONCLUSION: This systematic review demonstrates that a number of ESS simulators have been comprehensively validated. Many of the validation processes, however, lack standardisation in outcome reporting, thus limiting a meta-analysis comparison between simulators.

Pathophysiology of swallowing following oropharyngeal surgery for obstructive sleep apnea syndrome.

BACKGROUND: Uvulopalatopharyngoplasty (UPPP) and coblation channeling of the tongue (CCT) are oropharyngeal surgeries used to treat obstructive sleep apnea syndrome. The extent to which UPPP and CCT affect pharyngeal swallow has not been determined. We therefore conducted a novel case series study employing high-resolution impedance manometry (HRIM) to quantify the swallowing-related biomechanics following UPPP and/or CCT surgery. METHODS: Twelve patients who underwent UPPP+CCT or CCT only were assessed an average 2.5 years postsurgery. Swallow function data were compared with ten healthy controls. All patients completed the Sydney swallow questionnaire (SSQ). Pharyngeal pressure-flow analysis of HRIM recordings captured key distension, contractility and pressure-flow timing swallow parameters testing 5, 10, and 20 mL volumes of thin and thick fluid consistencies. KEY RESULTS: Postoperative patients had more dysphagia symptoms with five returning abnormal SSQ scores. Swallowing was biomechanically altered compared to controls, consistent with diminished swallowing reserve, largely driven by elevated hypopharyngeal intrabolus pressure due to a reduced capacity to open the upper esophageal sphincter to accommodate larger volumes. CONCLUSIONS & INFERENCES: Patients who have undergone UPPP and/or CCT surgery appear to have a deficiency in normal modulation of the swallowing mechanism and a reduced swallowing functional reserve. We speculate that these changes may become relevant in later life with the onset of age-related stressors to the swallowing mechanism. This case series strikes a note of caution that further studies are needed to determine the role of preoperative swallow assessment in patients undergoing UPPP and/or CCT surgery.

Penetrating neck injuries: a guide to evaluation and management.

Introduction Penetrating neck injury is a relatively uncommon trauma presentation with the potential for significant morbidity and possible mortality. There are no international consensus guidelines on penetrating neck injury management and published reviews tend to focus on traditional zonal approaches. Recent improvements in imaging modalities have altered the way in which penetrating neck injuries are now best approached with a more conservative stance. A literature review was completed to provide clinicians with a current practice guideline for evaluation and management of penetrating neck injuries. Methods A comprehensive MEDLINE (PubMed) literature search was conducted using the search terms 'penetrating neck injury', 'penetrating neck trauma', 'management', 'guidelines' and approach. All articles in English were considered. Articles with only limited relevance to the review were subsequently discarded. All other articles which had clear relevance concerning the epidemiology, clinical features and surgical management of penetrating neck injuries were included. Results After initial resuscitation with Advanced Trauma Life Support principles, penetrating neck injury management depends on whether the patient is stable or unstable on clinical evaluation. Patients whose condition is unstable should undergo immediate operative exploration. Patients whose condition is stable who lack hard signs should undergo multidetector helical computed tomography with angiography for evaluation of the injury, regardless of the zone of injury. Conclusions The 'no zonal approach' to penetrating neck trauma is a selective approach with superior patient outcomes in comparison with traditional management principles. We present an evidence-based, algorithmic and practical guide for clinicians to use when assessing and managing penetrating neck injury.

Survival outcomes following salvage surgery for oropharyngeal squamous cell carcinoma: systematic review.

BACKGROUND: Recurrent oropharyngeal squamous cell carcinoma causes great morbidity and mortality. This systematic review analyses survival outcomes following salvage surgery for recurrent oropharyngeal squamous cell carcinoma. METHODS: A comprehensive search of various electronic databases was conducted. Studies included patients with recurrent or residual oropharyngeal squamous cell carcinoma treated with salvage surgery. Primary outcomes were survival rates following salvage surgery. Secondary outcomes included time to recurrence, staging at time of recurrence, post-operative complications, and factors associated with mortality and recurrence. Methodological appraisal and data extraction were conducted as per Joanna Briggs Institute methodology. RESULTS: Eighteen articles were included. The two- and five-year survival rates of the patients were 52 per cent and 30 per cent respectively. CONCLUSION: Improvements in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were associated with improvements in two-year overall survival rates, with minimal change to five-year overall survival rates. Various factors were identified as being associated with long-term overall survival, thus assisting clinicians in patient counselling and selection for salvage surgery.

Cost analysis of injection laryngoplasty performed under local anaesthesia versus general anaesthesia: an Australian perspective.

OBJECTIVE: To conduct a cost analysis of injection laryngoplasty performed in the operating theatre under local anaesthesia and general anaesthesia. METHODS: The retrospective study included patients who had undergone injection laryngoplasty as day cases between July 2013 and March 2016. Cost data were obtained, along with patient demographics, anaesthetic details, type of injectant, American Society of Anesthesiologists score, length of stay, total operating theatre time and surgeon procedure time. RESULTS: A total of 20 cases (general anaesthesia = 6, local anaesthesia = 14) were included in the cost analysis. The mean total cost under general anaesthesia (AU$2865.96 ± 756.29) was significantly higher than that under local anaesthesia (AU$1731.61 ± 290.29) (p < 0.001). The mean operating theatre time, surgeon procedure time and length of stay were all significantly lower under local anaesthesia compared to general anaesthesia. Time variables such as operating theatre time and length of stay were the most significant predictors of the total costs. CONCLUSION: Procedures performed under local anaesthesia in the operating theatre are associated with shorter operating theatre time and length of stay in the hospital, and provide significant cost savings. Further savings could be achieved if local anaesthesia procedures were performed in the office setting.

Validity of the American College of Surgeons' National Surgical Quality Improvement Program risk calculator in South Australian glossectomy patients.

BACKGROUND: Appropriate selection of tongue cancer patients considering surgery is critical in ensuring optimal outcomes. The American College of Surgeons' National Surgical Quality Improvement Program ('ACS-NSQIP') risk calculator was developed to assess patients' 30-day post-operative risk, providing surgeons with information to guide decision making. METHOD: A retrospective review of 30-day actual mortality and morbidity of tongue cancer patients was undertaken to investigate the validity of this tool for South Australian patients treated from 2005 to 2015. RESULTS: One hundred and twenty patients had undergone glossectomy. Predicted length of stay using the risk calculator was significantly different from actual length of stay. Predicted mortality and other complications were found to be similar to actual outcomes. CONCLUSION: The American College of Surgeons' National Surgical Quality Improvement Program risk calculator was found to be effective in predicting post-operative complication rates in South Australian tongue cancer patients. However, significant discrepancies in predicted and actual length of stay may limit its use in this population.

A comparative study of voice outcomes and complication rates in patients undergoing injection laryngoplasty performed under local versus general anaesthesia: an Adelaide voice specialist's experience.

OBJECTIVE: To compare clinical outcomes and complication rates in patients undergoing injection laryngoplasty performed under local versus general anaesthesia. METHODS: A retrospective review was conducted of patients who underwent injection laryngoplasty performed by a single laryngologist in a tertiary Australian laryngology centre, between February 2013 and December 2014. Patient demographics, anaesthetic modality and complications were recorded. Voice Handicap Index 10 and the Grade, Breathiness, Roughness, Asthenia, Strain scale were evaluated. RESULTS: Thirty-four laryngoplasties were performed under general anaesthesia and 41 under local anaesthesia, with mean patient ages of 59.5 and 68.8 years, respectively. Voice Handicap Index 10 scores were significantly improved post-injection (p 0.05). All aspects of the Grade, Breathiness, Roughness, Asthenia, Strain scale showed significant improvement post-injection, except asthenia. There were seven (9.3 per cent) minor complications (five in the general anaesthesia group, two in the local anaesthesia group), all managed conservatively. CONCLUSION: Injection laryngoplasties performed under general anaesthesia and local anaesthesia offer similar voice outcomes, with comparable complication rates. Hence, development of a management algorithm for injection laryngoplasties performed under local anaesthesia is recommended.

Hyaluronic acid for post sinus surgery care: systematic review and meta-analysis.

BACKGROUND: Wound healing after endoscopic sinus surgery may result in adhesion formation. Hyaluronic acid may prevent synechiae development. A systematic review was performed to evaluate the current evidence on the clinical efficacy of hyaluronic acid applied to the nasal cavity after sinus surgery. METHODS: Studies using hyaluronic acid as an adjunct treatment following endoscopic sinus surgery for chronic rhinosinusitis were identified. The primary outcome was adhesion formation rates. A meta-analysis was performed on adhesion event frequency. Secondary outcome measures included other endoscopic findings and patient-reported outcomes. RESULTS: Thirteen studies (501 patients) met the selection criteria. A meta-analysis of adhesion formation frequency on endoscopy demonstrated a lower risk ratio in the hyaluronic acid intervention group (42 out of 283 cases) compared to the control group (81 out of 282) of 0.52 (95 per cent confidence interval = 0.37-0.72). Hyaluronic acid use was not associated with any significant adverse events. CONCLUSION: Hyaluronic acid appears to be clinically safe and well tolerated, and may be useful in the early stages after sinus surgery to limit adhesion rate. Further research, including larger randomised controlled trials, is required to evaluate patient- and clinician-reported outcomes of hyaluronic acid post sinus surgery.