The role of methadone in cancer-induced bone pain: a retrospective cohort study.

PURPOSE: Cancer-induced bone pain (CIBP) can be challenging to manage in advanced cancer. The unique properties of methadone may have a role in refractory CIBP. We aimed to evaluate the analgesic effects of methadone for CIBP when other opioids are ineffective or intolerable. METHODS: A retrospective study of palliative care inpatients rotated to methadone from another opioid for CIBP over a 4-year period. Primary outcome was ≥ 30% reduction in pain intensity (11-point numeric rating scale) from baseline to completion of methadone rotation (MR). Secondary outcomes were ≥ 50% reduction in pain intensity and changes in long-acting and breakthrough opioid requirements. RESULTS: Ninety-four eligible patients completed MR for the following reasons: poor pain control (72.3%), opioid toxicities (4.3%) or both (23.4%). On completion of MR, 70.2% and 53.2% achieved a ≥ 30% and ≥ 50% reduction in pain respectively, with mean pain intensity score reduced from 5.6 (SD = 2.1) at baseline to 2.6 (SD = 2.5) (p < 0.001). Mean calculated daily methadone dose pre-MR was 25.7 mg (SD = 10.9), with 72.3% of patients requiring a lower dose on completion of MR (mean 17.0 mg, SD = 8.5). The mean number of breakthrough opioid analgesia used a day reduced from 3.4 (SD = 2.3) to 1.8 (SD = 1.7) (p < 0.001). CONCLUSIONS: MR for CIBP may result in reduction in pain intensity, when other opioids are ineffective or intolerable, with patients requiring reduced overall dosing of their long-acting opioid and frequency of breakthrough opioid use.

Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.

OBJECTIVES: Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. METHODS: We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. RESULTS: We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. CONCLUSION: SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.

Risk of malignancy in incidental oropharyngeal lesions exhibiting fluorodeoxyglucose uptake which proceed to tissue biopsy.

BACKGROUND: Utilization of positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose is increasing in use for a variety of indications, including surveillance of cancer patients. There is a paucity of evidence pertaining to the significance of incidental PET-avid oropharyngeal lesions. This study aims to examine the clinical and radiological features of these incidental oropharyngeal lesions in patients undergoing PET for indications other than head and neck cancer. METHODS: Retrospective cohort study of three Australian tertiary hospitals, from 2015 to 2021, on adult patients undergoing biopsy of incidental PET-avid oropharyngeal lesions. Primary outcome of interest was the incidence of malignancy. Patients with a previous history of, or undergoing investigations for, head and neck cancer were excluded. RESULTS: Thirty-one patients were included, wherein 21 patients had tonsillar uptake, and 13 patients had base of tongue uptake. Tonsillar disease was mostly asymmetrical (n = 15/21), bilateral (n = 11/21), and had median SUVmax 9.35 (n = 12, IQR 7.4-11.15). Base of tongue was mostly asymmetrical (n = 7/13, 54%), bilateral (n = 8/13, 62%), and had median SUVmax 8.2 (n = 10, IQR 6.9-12.65). Seven patients had malignancy confirmed on tissue biopsy: five biopsies confirmed the tissue diagnosis of suspected lymphoma, and two incidental findings of unexpected malignancies: one p16 positive tonsillar squamous cell carcinoma, and one metastatic breast cancer. CONCLUSION: In 31 patients undergoing tissue biopsy for incidental PET-avid oropharyngeal lesions, there were two unexpected malignancies. Our study results indicate that although unexpected malignancies are uncommon, a malignant diagnosis cannot be excluded from clinical features alone.

Systematic Review of Intracochlear Measurements and Effect on Postoperative Auditory Outcomes after Cochlear Implant Surgery.

OBJECTIVE: Quality and adequacy of the electrode neuron interface (ENI) is postulated to be a determining factor in affecting auditory outcomes after cochlear implantation. This study aims to review radiological parameters affecting ENI, including angular insertion (AngI), wrapping factor (WF), scalar translocation (ScaT), and electrode-modiolar distance (EMD) and their effect on auditory outcomes. DATABASES REVIEWED: PubMed, MEDLINE, Embase, Scopus, OpenGrey, and Google Scholar from inception to 01 September 2022. METHODS: Inclusion criteria were (i) all humans with any cochlear implant (CI); (ii) postoperative cross-sectional imaging with electrode position factors of AngI, ScaT, EMD, and/or WF; and (iii) associated auditory outcomes. Search was restricted to English-language literature. Two independent reviewers performed title and abstract screening, data extraction, and ROBINS-I risk of bias assessment. Formal statistical analysis not performed due to data heterogeneity. PROSPERO (CRD42022359198). RESULTS: Thirty-one studies (n = 2,887 patients, 3,091 electrodes) underwent qualitative synthesis. Higher AngI (n = 1921 patients) demonstrated positive correlation in 11 studies, no correlation in eight studies, and negative correlation in four studies. ScaT (n = 2,115 patients) demonstrated negative correlation in 12 studies, none in six studies, and one unclear correlation. Larger EMD (n = 240 patients) showed negative correlation in two studies, no correlation in one, and unclear correlation in one study. Smaller WF (n = 369 patients) demonstrated no correlation in three studies and positive correlation in one study. CONCLUSIONS: Our study finds variable reported relationship between AngI and auditory outcomes. CI electrodes with a ScaT or larger EMD are more likely to exhibit poorer outcomes, and WF does not correlate with outcomes.

Systematic Review and Meta-Analysis of a New Active Transcutaneous Bone Conduction Implant.

OBJECTIVE: This review aims to quantify the pooled functional gain (FG) in different types of hearing loss with the transcutaneous hearing device, Osia (Cochlear, Sydney, Australia) in comparison with the unaided state. Secondary outcomes are patient-reported outcomes measures (PROMs) and complication rates. DATA SOURCES: Medline, Embase, SCOPUS, Cochrane CENTRAL, PROSPERO and Cochrane Library. REVIEW METHODS: Systematic review and meta-analysis of indexed search terms relating to "Osia," "Osseointegration," "Cochlear Implant," and "Bone-Anchored Prosthesis" was performed from database inception to September 20, 2022. RESULTS: Of the 168 studies identified, 14 studies with 15 patient cohorts (n = 314) met inclusion criteria for meta-analysis. Pooled overall mean FG for all types of hearing loss was 35.0 dB sound pressure level (SPL) (95% confidence interval [CI] 29.12-40.97) compared against unaided hearing. Pooled FG for conductive/mixed hearing loss was 37.7 dB SPL (95% CI 26.1-49.3). Pooled single-sided deafness (SSD) FG could not be calculated due to the small patient cohort for whom SSD data was reported. There is a trend toward improvements in speech receptiveness threshold, signal to noise ratio, and some PROMs compared with baseline hearing. Early complication rates demonstrate risks similar to other transcutaneous implants, with a low predicted explantation (0.11%, 95% CI 0.00%-1.90%) and wound infection rate (1.92% [95% CI 0.00%-6.17%]). No articles directly comparing transcutaneous devices were identified. CONCLUSION: The Osia devices demonstrate clear audiologic benefits and a good safety profile for the included patient population. Our study results indicate that frequency-specific gain, PROMs, and the audiological benefit in single-sided deafness may be areas for future prospective research. Laryngoscope, 134:1531-1539, 2024.

Molecular Factors in Carcinoma Ex Pleomorphic Adenoma: Systematic Review and Meta-Analysis.

OBJECTIVE: Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis. DATA SOURCES: MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. REVIEW METHODS: Systematic review and meta-analysis from inception to October 31, 2022 for all English language studies pertaining to "carcinoma ex pleomorphic adenoma." Predicted incidence of each biomarker was calculated with meta-analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies. RESULTS: Of 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a-SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c-kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies. CONCLUSION: Molecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 134:1042-1053, 2024.

A Deep Learning Algorithm to Identify Anatomical Landmarks on Computed Tomography of the Temporal Bone.

BACKGROUND: Petrous temporal bone cone-beam computed tomography scans help aid diagnosis and accurate identification of key operative landmarks in temporal bone and mastoid surgery. Our primary objective was to determine the accuracy of using a deep learning convolutional neural network algorithm to augment identification of structures on petrous temporal bone cone-beam computed tomography. Our secondary objective was to compare the accuracy of convolutional neural network structure identification when trained by a senior versus junior clinician. METHODS: A total of 129 petrous temporal bone cone-beam computed tomography scans were obtained from an Australian public tertiary hospital. Key intraoperative landmarks were labeled in 68 scans using bounding boxes on axial and coronal slices at the level of the malleoincudal joint by an otolaryngology registrar and board-certified otolaryngologist. Automated structure identification was performed on axial and coronal slices of the remaining 61 scans using a convolutional neural network (Microsoft Custom Vision) trained using the labeled dataset. Convolutional neural network structure identification accuracy was manually verified by an otolaryngologist, and accuracy when trained by the registrar and otolaryngologist labeled datasets respectively was compared. RESULTS: The convolutional neural network was able to perform automated structure identification in petrous temporal bone cone-beam computed tomography scans with a high degree of accuracy in both axial (0.958) and coronal (0.924) slices (P < .001). Convolutional neural network accuracy was proportionate to the seniority of the training clinician in structures with features more difficult to distinguish on single slices such as the cochlea, vestibule, and carotid canal. CONCLUSION: Convolutional neural networks can perform automated structure identification in petrous temporal bone cone-beam computed tomography scans with a high degree of accuracy, with the performance being proportionate to the seniority of the training clinician. Training of the convolutional neural network by the most senior clinician is desirable to maximize the accuracy of the results.

Convolutional Neural Networks in ENT Radiology: Systematic Review of the Literature.

INTRODUCTION: Convolutional neural networks (CNNs) represent a state-of-the-art methodological technique in AI and deep learning, and were specifically created for image classification and computer vision tasks. CNNs have been applied in radiology in a number of different disciplines, mostly outside otolaryngology, potentially due to a lack of familiarity with this technology within the otolaryngology community. CNNs have the potential to revolutionize clinical practice by reducing the time required to perform manual tasks. This literature search aims to present a comprehensive systematic review of the published literature with regard to CNNs and their utility to date in ENT radiology. METHODS: Data were extracted from a variety of databases including PubMED, Proquest, MEDLINE Open Knowledge Maps, and Gale OneFile Computer Science. Medical subject headings (MeSH) terms and keywords were used to extract related literature from each databases inception to October 2020. Inclusion criteria were studies where CNNs were used as the main intervention and CNNs focusing on radiology relevant to ENT. Titles and abstracts were reviewed followed by the contents. Once the final list of articles was obtained, their reference lists were also searched to identify further articles. RESULTS: Thirty articles were identified for inclusion in this study. Studies utilizing CNNs in most ENT subspecialties were identified. Studies utilized CNNs for a number of tasks including identification of structures, presence of pathology, and segmentation of tumors for radiotherapy planning. All studies reported a high degree of accuracy of CNNs in performing the chosen task. CONCLUSION: This study provides a better understanding of CNN methodology used in ENT radiology demonstrating a myriad of potential uses for this exciting technology including nodule and tumor identification, identification of anatomical variation, and segmentation of tumors. It is anticipated that this field will continue to evolve and these technologies and methodologies will become more entrenched in our everyday practice.

A Computer Vision Algorithm to Classify Pneumatization of the Mastoid Process on Temporal Bone Computed Tomography Scans.

BACKGROUND: Pneumatization of the mastoid process is variable and of significance to the operative surgeon. Surgical approaches to the temporal bone require an understanding of pneumatization and its implications for surgical access. This study aims to determine the feasibility of using deep learning convolutional neural network algorithms to classify pneumatization of the mastoid process. METHODS: De-identified petrous temporal bone images were acquired from a tertiary hospital radiology picture archiving and communication system. A binary classification mode in the pretrained convolutional neural network was used to investigate the utility of convolutional neural networks in temporal bone imaging. False positive and negative images were reanalyzed by the investigators and qualitatively assessed to consider reasons for inaccuracy. RESULTS: The overall accuracy of the model was 0.954. At a probability threshold of 65%, the sensitivity of the model was 0.860 (95% CI 0.783-0.934) and the specificity was 0.989 (95% CI 0.960-0.999). The positive predictive value was 0.973 (95% CI 0.904-0.993) and the negative predictive value was 0.935 (95% CI 0.901-0.965). The false positive rate was 0.006. The F1 number was 0.926 demonstrating a high accuracy for the model. CONCLUSION: The temporal bone is a complex anatomical region of interest to otolaryngologists. Surgical planning requires high-resolution computed tomography scans, the interpretation of which can be augmented with machine learning. This initial study demonstrates the feasibility of utilizing machine learning algorithms to discriminate anatomical variation with a high degree of accuracy. It is hoped this will lead to further investigation regarding more complex anatomical structures in the temporal bone.

Does intra-operative humidification with warmed CO2 reduce surgical site infection in open colorectal surgery? A randomized control trial.

BACKGROUNDS: Surgical site infections (SSI) are a significant cause of postoperative morbidity and mortality, contributing to a considerable financial burden on the healthcare system. Insufflation of the open surgical wound with warm, humidified carbon dioxide (CO2 ) is a novel measure aimed to reduce SSI. The local atmosphere of warm, humidified CO2 within the open surgical wound is proposed to decrease airborne contamination, bacterial growth, desiccation, and heat loss while improving tissue oxygenation and perfusion. This randomized controlled trial evaluates the impact of the HumiGard™ surgical humidification system on the incidence of SSI in patients undergoing open colorectal surgery. METHODS: We conducted a multi-site single-blinded randomized control trial on patients undergoing elective or emergency laparotomy at a single tertiary Colorectal Surgery service. The primary outcome measure was the incidence of SSI, with secondary outcomes including ICU length of stay (LOS), total LOS and mean core temperature. RESULTS: Patients who received HumiGard™ had a lower incidence of SSI, although this did not reach statistical significance (4.5% for treatment group versus 13.0% for control group; P = 0.092). There was no significant difference in ICU LOS or total LOS between cohorts. The HumiGard™ group had a higher mean core temperature than the control at the end of surgery (P < 0.001). CONCLUSION: The present study could not confirm that utilization of warm, humidified CO2 with HumiGard™ reduces SSI in open colorectal surgery. Further research is indicated to validate and extend these findings.

Cost-minimisation analysis of polysomnography and pulse oximetry in a risk stratification protocol for paediatric adenotonsillectomy.

BACKGROUND: Severe obstructive sleep apnoea (OSA) is associated with increased risk of respiratory compromise in the post-operative period following adenotonsillectomy (AT). This study analyses the economic cost of polysomnography or overnight oximetry as part of pre-operative risk stratification in paediatric AT, supplementing previously published research demonstrating the efficacy of this protocol in predicting respiratory complications. METHODS: This cost-minimisation analysis examines costs associated with pre-operative overnight oximetry and polysomnography in triaging paediatric patients older than 2 years old, with no major comorbidities except for OSA, undergoing AT for OSA (n = 1801) to either a secondary or quaternary Australian hospital. Decision analysis modelling via probability trees were utilized to estimate pre- and peri-operative costs. A third hypothetical 'no investigation' model based upon conducting all AT at a secondary hospital was performed. Costs are derived from the financial year 2020-2021, censored at discharge. RESULTS: The total cost per patient of AT including pre-operative investigations of oximetry and polysomnography, and associated inpatient costs, were AUD4181.34 and 5013.99 respectively. This is more expensive compared to a hypothetical no-investigation model (AUD3958.98). CONCLUSION: Within the scope of this partial economic evaluation, this study finds a small additional cost for a model of care involving overnight oximetry as a pre-operative triage tool, balanced by the reduced cost of care in a lower acuity centre for low-risk patients and potential high cost of complications if all children are treated in a low acuity centre. This supports oximetry in peri-operative risk stratification for paediatric AT from a financial perspective.

Paediatric tonsillectomy and adenotonsillectomy in a rural setting: a retrospective study over a period of 6-years.

BACKGROUND: Swan Hill District Health (SHDH) provides Otolaryngological services to outer regional Victoria. A preoperative checklist determines eligibility for tonsillectomy, and the role of preoperative investigations such as oximetry. Visiting specialists who provide T&A also remain on-site for 24 h post-surgery. Management of post-discharge complications is supported by SHDH's Emergency Department. Unstable patients are transferred to tertiary care hospitals. This study examines the safety outcomes associated with rural Tonsillectomy and adenotonsillectomy (T&A) and the impact of peri-operative protocols on these outcomes. METHODS: This is a retrospective cohort study of all paediatric (2-18 years old) patients undergoing T&A from August 2014 to June 2020 at SHDH. Four external hospital databases which accept patient transfers from SHDH were searched for T&A-related complications. The primary outcome was complication incidence. Secondary outcomes were length of stay, and rates of hospital readmissions, return to theatre and inter-hospital transfer. RESULTS: Two hundred and four patients were included, with median age 6 years old; 68.1% (n = 139/204) had obstructive sleep apnoea, or sleep disordered breathing, wherein 36.0% (n = 50/139) had documented evidence of normal/inconclusive oximetry. The complication rate is 6.9% (n = 14/204), with two intraoperative, five perioperative and seven post-discharge complications. All intra- and peri-operative complications were managed locally. All post-discharge complications presented to outer regional EDs. Two patients required inter-hospital transfer for monitoring of post-tonsillectomy bleeds in a specialist unit. CONCLUSIONS: Patients who pass a preoperative risk checklist can safely undergo T&A in selected rural settings which adhere to strict patient selection criteria and implement safety measures to address complications.

Systematic review of prognostic factors in carcinoma ex pleomorphic adenoma.

OBJECTIVES: Carcinoma ex Pleomorphic Adenoma (CXPA) is a rare primary salivary gland malignancy, typically arising from a pre-existing pleomorphic adenoma. This systematic review examines prognostic factors affecting overall survival (OS) in major and minor salivary gland CXPA. MATERIALS AND METHODS: Systematic review of MEDLINE, Cochrane, Scopus, Web of Science, CINAHL, and Open Grey databases from inception to 31st March 2022 for all English-language literature pertaining to 'carcinoma ex pleomorphic adenoma'. All study types with greater than five patients with CXPA of the major and minor salivary glands were eligible for inclusion. RESULTS: Of 8143 studies, 39 studies (n = 5637 patients) meeting the inclusion criteria were included. Median OS at one, three, five, and ten years were 90.0 %, 72.0 %, 61.9 %, and 45.0 % respectively for all CXPA. Higher staging, T stage, nodal disease, grading, and invasion ≥ 1.5 mm had worse outcomes. Histological subtype, perineural invasion, and radiotherapy did not demonstrate a consistent trend. Three studies were evaluated to have high risk of bias, and was removed for sensitivity analysis. CONCLUSION: Survival outcomes worsen with time for all salivary gland CXPA. Further research on histopathological features and the utility of radiation therapy is required to guide patient selection for more aggressive treatment. REGISTRATION: CRD42021238544 (PROSPERO).

Systematic review and meta-analysis of cervical metastases in oral maxillary squamous cell carcinoma.

BACKGROUND: Management of the node-negative neck in oral maxillary squamous cell carcinoma (SCC), encompassing the hard palate and upper alveolar subsites of the oral cavity, is controversial, with no clear international consensus or recommendation regarding elective neck dissection in the absence of cervical metastases. AIM: To assess the occult metastatic rate in patients with clinically node negative oral maxillary SCC; both as an overall metastatic rate, and a comparison of patients managed with an elective neck dissection at index surgery, compared to excision of the primary with clinical observation of the neck. METHODS AND RESULTS: A systematic review was performed by two independent investigators for studies relating to oral maxillary SCC and analysed according to PRISMA criteria. Data were extracted from Pubmed, Ovid MEDLINE, EMBASE, and SCOPUS via relevant MeSH terms. Grey literature was searched through Google Scholar and OpenGrey. Five hundred and fifty-three articles were identified on the initial search, 483 unique articles underwent screening against eligibility criteria, and 29 studies were identified for final data extraction. Incidence of occult metastases in patients with clinically node negative oral maxillary SCC was identified either on primary elective neck dissection or on routine follow up. Meta-analyses were performed. Of 553 relevant articles identified on initial search, 29 were included for analysis. The pooled overall rate of occult metastases in patients initially presenting with clinically node-negative disease was 22.2%. There is a statistically significant effect of END on decreasing regional recurrence demonstrated in this study (RR 0.36, 95% CI 0.24, 0.59). CONCLUSION: The results of this systematic review and meta-analysis suggest elective neck dissection for patients presenting with hard palate or upper alveolar SCC, even in a clinically node negative neck.