A Novel CRISPR/Cas9-mediated mouse model of colon carcinogenesis.

BACKGROUND & AIMS: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. AIMS: Generate a sporadic CRC model that more closely mimics this multi-step process and use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis. METHODS: We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed for simultaneous inactivation of multiple genes involved in CRC pathogenesis. We used both a doxycycline-inducible transcriptional activator and a dox-inactivated transcriptional repressor to achieve tight, non-leaky expression of the Cas9 nickase. This mouse has transgenic expression of multiple guide RNAs to induce sporadic inactivation in the gut epithelium of four tumor suppressor genes commonly mutated in CRC, Apc, Pten, Smad4 and Trp53. These were crossed to Vil-LCL-PLAGL2 mice which have Cre-inducible overexpression of PLAGL2 in the gut epithelium. RESULTS: These mice exhibited random somatic mutations in all four targeted tumor suppressor genes, resulting in multiple adenomas and adenocarcinomas in the small bowel and colon. Crosses with Vil-LCL-PLAGL2 mice demonstrated that gut-specific PLAGL2 overexpression increased colon tumor growth. CONCLUSIONS: This conditional model represents a new CRISPR/Cas9-mediated mouse model of colorectal carcinogenesis. These mice can be used to investigate the role of novel, previously uncharacterized genes in CRC, in the context of multiple commonly mutated tumor suppressor genes and thus more closely mimic human CRC pathogenesis.

Revised Diagnosis From Histiocytic Neoplasm to Optic Chiasm Glioblastoma After Genetic Analysis.

ABSTRACT: A 46-year-old man presented with left eye blurring. Automated visual field testing showed an incongruous right hemianopia, with sparing of the lower temporal quadrant in the right eye. MRI revealed foci of gadolinium enhancement in the optic chiasm and optic tracts. Serologic testing (including myelin oligodendrocyte glycoprotein and neuromyelitis optica antibodies) and cerebrospinal fluid analysis were negative. Whole-body PET/CT scan found no malignancy. Biopsy of the optic chiasm revealed a moderately cellular neoplasm composed of atypical, discohesive cells with enlarged nuclei, prominent eosinophilic nucleoli, and abundant vacuolated cytoplasm. Immunohistochemical stains for CD68 and S100 were positive, whereas those for GFAP, OLIG2, SOX10, and multiple others were negative, supporting a diagnosis of histiocytic neoplasm. Five weeks later, results became available from next-generation sequencing targeting the coding regions of hundreds of malignancy-associated genes and select introns. Alterations associated with histiocytic neoplasms (i.e. BRAF and MAP2K1 mutations) were absent. However, there was a nonsense mutation in the PTEN gene, a hotspot mutation in the TERT gene promotor, and focal amplifications of the CDK4 and MDM2 genes. Additionally, there was chromosome 6q loss, 7 gain, and 10q loss. Based on these findings, the diagnosis was revised to glioblastoma, IDH-wildtype, CNS WHO grade 4. The patient began treatment with temozolomide while continuing radiation therapy. This case illustrates how next-generation sequencing can at times provide more accurate diagnostic information than standard tissue histopathology.

Cartilage-Sparing Otoplasty: An Overview of the Mustardé and Furnas Suture Techniques.

Otoplasty is commonly used to treat prominauris. Cartilage-sparing techniques for otoplasty are well popularized. The most common cartilage-sparing otoplasty techniques include the Mustardé and Furnas techniques. This article discusses the preparation, surgical steps, postoperative care, and associated complications for Mustardé and Furnas otoplasty in detail.

Quantifying surgical completeness in patients with aspirin exacerbated respiratory disease.

BACKGROUND: Aspirin exacerbated respiratory disease (AERD) in patients who have had sinus surgery remains a management challenge. Aspirin desensitization and biologics are additional treatment options. It remains unclear if patients require a more comprehensive surgery prior to implementing such additional therapies. The purpose of this study was to quantify prior surgery completeness in AERD patients at a tertiary rhinology practice. METHODS: Paranasal sinus CT scans were reviewed by four academic rhinologists to assess surgery completeness. Using a published CT grading system, each sinus was graded on the completeness of surgery and middle turbinate reduction. A score out of 14 was calculated for each patient (7 per side). RESULTS: Sixty-one patients with AERD out of 141 available were included. Mean inter-rater agreement across all sinuses was moderate (k = 0.42). The mean completeness score was 6.7/14. The following procedures were rated as complete (means): uncinectomy (L: 84%, R: 82%, k = 0.44), maxillary (L: 83%, R: 77%, k = 0.32), middle turbinate reduction (L: 45%, R: 46%, k = 0.31), anterior ethmoid (L: 35%, R: 39%, k = 0.51), sphenoid (L: 36%, R: 35%, k = 0.4), posterior ethmoid (L: 30%, R: 30%, k = 0.48), frontal (L: 22%, R: 21%, k = 0.46). CONCLUSION: Prior surgery in AERD patients were mostly deemed incomplete. Uncinectomy and maxillary antrostomy are the most common procedures previously performed. It remains toe seen whether this would be considered 'adequate' surgery or more 'complete' surgery is required to achieve greater disease control.

Anterior segment ischemia following strabismus surgery in a young adult using gender-affirming estrogen hormone therapy.

Well-known risk factors for anterior segment ischemia (ASI) following strabismus surgery include ipsilateral surgery on three or more rectus muscles, older age, and vasculopathy. ASI is rarely reported in young patients following uneventful strabismus surgery on two ipsilateral rectus muscles. We report a 30-year-old transgender female on long-term estrogen therapy who underwent strabismus surgery involving recessions of both lateral rectus muscles, the right inferior rectus muscle, and the left superior rectus muscle. The left eye developed severe ASI with hypotony maculopathy that was resistant to topical medications, oral steroids, anterior chamber reformation, and intravitreal steroid injection. Following phacoemulsification with intraocular lens and capsular tension ring insertion 1 year later, intraocular pressure and hypotony maculopathy improved.

The educational value of thyroidectomy YouTube videos for surgical trainees.

OBJECTIVE: To evaluate the usefulness of thyroidectomy videos posted on YouTube for surgical training. METHODS: The following keywords were searched on YouTube: "thyroidectomy", "conventional thyroidectomy", "hemithyroidectomy", and "thyroid lobectomy". The first 30 videos from each search were selected for a total of 120 videos. Included videos were those displaying a conventional approach to thyroidectomy and real, non-animated patient surgery. Two independent reviewers assessed each video using the LAParoscopic surgery Video Educational Guidelines (LAP-VEGaS) and a thyroidectomy-specific grading score (TSS). RESULTS: The search yielded 22 videos that met the selection criteria. The inter-rater agreement was excellent for the grading systems (ICC = 0.910). The average LAP-VEGaS score was of medium quality (8.82 ± 3.56 standard deviation (SD)). The highest average score (11.00 ± 1.68 SD) was assigned to videos published from academic institutions. There was no statistically significant difference in LAP-VEGaS scores when comparing the type of publisher between videos (p = 0.132). The majority of the videos (12/22, 55 %) did not include all hallmarks of thyroidectomy according to the novel TSS score. There was a significant positive correlation between TSS markers and the overall LAP-VEGaS score (r = 0.577, p = 0.005). CONCLUSION: YouTube videos as an educational resource for thyroidectomy instructions vary in quality. Most of the thyroidectomy videos were medium quality according to the LAP-VEGaS score. YouTube sourced thyroidectomy videos should be used to supplement traditional educational methods.

A critical readability and quality analysis of internet-based patient information on neck dissections.

Objective: Patients are increasingly turning to the Internet as a source of healthcare information. Given that neck dissection is a common procedure within the field of Otolaryngology - Head and Neck Surgery, the aim of this study was to evaluate the quality and readability of online patient education materials on neck dissection. Methods: A Google search was performed using the term "neck dissection." The first 10 pages of a Google search using the term "neck dissection" were analyzed. The DISCERN instrument was used to assess quality of information. Readability was calculated using the Flesch-Reading Ease, Flesch-Kincaid Grade Level, Gunning-Fog Index, Coleman-Liau Index, and Simple Measure of Gobbledygook Index. Results: Thirty-one online patient education materials were included. Fifty-five percent (n = 17) of results originated from academic institutions or hospitals. The mean Flesch-Reading Ease score was 61.2 ± 11.9. Fifty-two percent (n = 16) of patient education materials had Flesch-Reading Ease scores above the recommended score of 65. The average reading grade level was 10.5 ± 2.1. The average total DISCERN score was 43.6 ± 10.1. Only 26% of patient education materials (PEMs) had DISCERN scores corresponding to a "good quality" rating. There was a significant positive correlation between DISCERN scores and both Flesch-Reading Ease scores and average reading grade level. Conclusions: The majority of patient education materials were written above the recommended sixth-grade reading level and the quality of online information pertaining to neck dissections was found to be suboptimal. This research highlights the need for patient education materials regarding neck dissection that are high quality and easily understandable by patients.

Cannabis use amongst tinnitus patients: consumption patterns and attitudes.

BACKGROUND: Tinnitus has a significant impact on quality of life and causes considerable psychological distress. Cannabis is known to modulate neuron hyperexcitability, provide protection against auditory damage, and has been used for treatment for many diseases which have physiological similarities with tinnitus. The objective of this study was to survey patients presenting with tinnitus regarding their perspectives and usage patterns of cannabis. METHODS: Patients with a primary presenting complaint of tinnitus in a tertiary neuro-otology clinic completed a 18-item questionnaire assessing perception, attitudes, and cannabis usage patterns. RESULTS: Forty five patients completed the survey (mean age: 54.5 years, 31 females and 14 males). Overall, 96% of patients reported that they would consider cannabis as treatment for their tinnitus. Patients considered cannabis use for auditory symptoms (91%), and symptoms related to their tinnitus, such as emotional complaints (60%), sleep disturbances (64%), and functional disturbances (56%). 36% of patients had previously used cannabis and 22% of patients reported cannabis use at the time of the study. 80% of patients that were actively using cannabis reported that it helped with tinnitus-related symptoms, such as dizziness, anxiety, bodily pain, and sleep disturbances. Most patients would prefer to use edibles (62%), tablet (58%) and cream (47%) formulations of cannabis. Patients were concerned about the cost (29%), potential physical health implications (53%) and psychosocial side effects (60%) of cannabis. Over half of patients learned about cannabis from a friend or family member and only 22% of patients learned about cannabis from a physician or nurse. CONCLUSION: Cannabis use is common amongst patients with tinnitus and current users of cannabis reported that it helped with their symptoms. Most patients would consider its use as a potential treatment to alleviate their tinnitus-related symptoms and are interested in learning more regarding its use. By understanding how cannabis is perceived by tinnitus patients, healthcare providers can provide appropriate patient education.

Post-operative survival in head and neck cancer patients with elevated troponins.

OBJECTIVES: The strenuous demands of head and neck cancer surgery (HNS) place patients at increased risk of myocardial injury. Troponin positivity (TP) post-operatively is a predictor of increased complications and mortality. The present study is the first to investigate the effects of TP on potential delays in adjuvant treatment and disease-specific survival. DESIGN, SETTING, PARTICIPANTS AND MAIN OUTCOME MEASURES: All patients undergoing HNS from 2014 to 2016 had troponins measured at a single academic centre. Relevant patient data was extracted on retrospective chart review. The main outcome measures were the impact of TP on timing of adjuvant treatment and disease-specific survival. RESULTS: Of 166 patients, 26 (15.6%) developed TP post-operatively. There was no significant difference between cohorts for baseline characteristics except for age. Overall and disease-specific survival for TP patients were respectively 45.9% and 57.4% at 3 years. There was no significant difference between cohorts for overall and disease-specific survival, and time to adjuvant therapy. CONCLUSION: No significant association was found between TP and overall and disease-specific survival, and time to adjuvant therapy.

Clinicopathological Predictors of Survival for Parotid Mucoepidermoid Carcinoma: A Systematic Review.

OBJECTIVE: Various prognostic factors are associated with the survival of patients with parotid mucoepidermoid carcinoma (MEC). The aim of this systematic review is to summarize the clinical and pathologic prognostic factors on survival outcomes in patients with parotid MEC. DATA SOURCES: Articles published from database inception to July 2020 on OVID Medline, OVID Embase, Cochrane Central, and Scopus. REVIEW METHODS: Studies were included that reported clinical or pathologic prognostic factors on survival outcomes for adult patients with parotid MEC. Data extraction, risk of bias, and quality assessment were conducted by 2 independent reviewers. RESULTS: A total of 4290 titles were reviewed, 396 retrieved for full-text screening, and 18 included in the review. The average risk of bias was high, and quality assessment for the prognostic factors ranged from very low to moderate. Prognostic factors that were consistently associated with negative survival outcomes on multivariate analysis included histologic grade (hazard ratio [HR], 5.66), nodal status (HR, 2.86), distant metastasis (HR, 3.10-5.80), intraparotid metastasis (HR, 13.52), and age (HR, 1.02-6.86). Prognostic factors that inconsistently reported associations with survival outcomes were TNM stage, T classification, and N classification. CONCLUSION: Histologic grade, nodal status, distant metastasis, intraparotid metastasis, and age were associated with worse survival outcomes. These prognostic factors should be considered when determining the most appropriate treatment and follow-up plan for patients with parotid MEC.

Attitudes Toward and Acceptability of Medical Marijuana Use Among Head and Neck Cancer Patients.

OBJECTIVE: This study aims to understand the attitudes toward marijuana in HNC patients. METHODS: A 17-question questionnaire regarding medical marijuana (MM) was distributed to HNC patients at a tertiary cancer center. RESULTS: 63 HNC patients completed the questionnaire. Patients that had used or were using marijuana described benefit with symptoms of headache, pain, nausea, and loss of appetite. 83% of all patients considered marijuana as treatment for cancer related pain and 67% as treatment for cancer related anxiety. About 70% of patients actively undergoing cancer treatment believed marijuana medications would help with symptoms during treatment. CONCLUSIONS: By understanding how HNC patients perceive MM, HNC teams may be able to prescribe and educate their patients on MM.

Validity and Usefulness of YouTube Videos Related to Endoscopic Transsphenoidal Surgery for Patient Information.

Objectives This article evaluates the completeness and accuracy of YouTube videos related to endoscopic transsphenoidal surgery (ETS) as a source for patient information. Design YouTube was searched using relevant terms pertaining to ETS. Videos were evaluated independently by two physician reviewers experienced in ETS. Video demographics including uploader source along with validity scores based on predetermined checklists were captured. Setting Internet. Participants Not applicable. Main Outcome Measures A novel ETS scoring checklist, the modified DISCERN criteria, and Journal of the American Medical Association (JAMA) benchmark score were used to measure completeness and accuracy of videos. video power index (VPI) was calculated to reflect popularity. Intraclass correlation coefficient was calculated for rater agreement. Results Seventy-nine videos were included in final scoring and analysis. The ETS score, DISCERN, JAMA, and mean VPI across all included videos were 5.0 ± 2.7, 2.4 ± 0.83, 2.19 ± 0.62, and 8.92 ± 18.1, respectively. Based on the ETS score checklist, 31 (39%) of the videos were rated as poor, 30 (38%) were moderately useful, 17 (22%) were useful, and 1 (1%) was exceptional. There was a significant positive correlation between the ETS, DISCERN, and JAMA scores ( p < 0.001), but no correlation with VPI and the validity scores. There were no significant differences comparing validity scores based on the uploader source. Conclusion YouTube videos related to ETS have limited usefulness and poor overall validity for patient information. Clinicians should direct patients to other validated sources of information and aim to improve the comprehensiveness of ETS-related videos.

Modalities of Post-Rhinoplasty Edema and Ecchymosis Measurement: A Systematic Review.

Background: Post-rhinoplasty edema and ecchymosis can influence patient satisfaction with surgery as well as result in poor quality of life. Methods to quantify such edema and ecchymosis have been described in the literature. Despite this, there is currently no collective understanding of which methods are the most effective. Hence, this systematic review aims to describe and analyze the literature on post-rhinoplasty edema and ecchymosis measurement techniques. Methods: Standard bibliographic databases (OVID Medline, EMBASE, and PubMed) were searched from their inception to December 2019 for the terms: "rhinoplasty", "postoperative", "edema", and "ecchymosis". Descriptive analysis was completed. Results: The search revealed 1116 articles of which 33 met inclusion criteria and were included for qualitative synthesis. A total of 1801 patients from all studies were included. Of the 33 included studies, there were 57 unique ecchymosis/edema measurements. The majority of studies measured edema/ecchymosis on post-operative day 1, 2, 3 and 7. Ninety-three percent of measurements described were taken subjectively from a human rater. Other techniques described included magnetic resonance imaging, ultrasound, 3-dimensional imaging, and digital analysis. Less than half of the subjective ecchymosis/edema gradings were completed by a blinded rater. Conclusion: There are a wide variety of post-rhinoplasty edema and ecchymosis techniques being used by rhinoplasty surgeons. The majority of post-rhinoplasty edema and ecchymosis measurements are completed by unblinded subjective raters. It is important that facial plastic surgeons select an accurate measurement tool so they may be able to initiate precise patient-specific management of edema and ecchymosis.

Historique: L'œdème et les ecchymoses après une rhinoplastie peuvent nuire à la satisfaction du patient envers l'opération et entraîner une mauvaise qualité de vie. Les publications contiennent des méthodes pour les quantifier. Pourtant, il n'y a actuellement aucune compréhension collective de la méthode la plus efficace. La présente analyse systématique vise à décrire et à analyser les publications sur les techniques de mesure de l'œdème et des ecchymoses après une rhinoplastie. Méthodologie: Les chercheurs ont fouillé les bases de données bibliographiques standards (OVID Medline, EMBASE et PubMed) à compter de leur création jusqu'à décembre 2019 au moyen des termes rhinoplasty, postoperative, edema et ecchymosis. Ils ont procédé à l'analyse descriptive. Résultats: La recherche a permis d'extraire 1 116 articles, dont 33 respectaient les critères d'inclusion et ont servi à la synthèse qualitative. Au total, 1 801 patients de toutes les études ont été retenus. Les 33 articles étudiés contenaient 57 mesures différentes des ecchymoses et de l'œdème. Dans la majorité des études, la mesure de l'œdème et des ecchymoses avait lieu le premier, le deuxième, le troisième et le septième jour après l'opération. Par ailleurs, 93% des mesures décrites avaient été prises de manière subjective par un évaluateur humain. Parmi les autres techniques décrites, soulignons l'imagerie par résonance magnétique, l'échographie, l'imagerie tridimensionnelle et l'analyse numérique. Moins de la moitié des évaluations subjectives des ecchymoses et de l'œdème avait été effectuée par un évaluateur en insu. Conclusion: Les chirurgiens spécialisés en rhinoplastie recourent à une vaste gamme de techniques pour mesurer l'œdème et les ecchymoses après une rhinoplastie. La majeure partie de ces mesures est effectuée par des évaluateurs subjectifs sans insu. Il est important que les chirurgiens faciaux choisissent un outil de mesure précis pour pouvoir entreprendre une prise en charge de l'œdème et des ecchymoses adaptée au patient.

Nasal Septal Perforation Reconstruction with Polydioxanone Plate: A Systematic Review.

Nasal septal perforation is an uncommon pathology that is difficult to surgically repair and may significantly impact patients' quality of life. Existing treatments have high complication and failure rates. The use of polydioxanone (PDS) plates to repair septal perforations is an innovative approach that has demonstrated superior outcomes to the conventional techniques. This study aimed to review the literature on PDS plates for nasal septal perforation reconstruction. PubMed, OVID Medline, and OVID Embase databases were searched for relevant articles in June 2021. Search terms included nasal septal perforation, polydioxanone, septal perforation, septal repair, nasal septum, and PDS plate. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were adhered to for this systematic review. Database searches yielded 80 articles. Seven articles were included representing 74 patients. All studies reported the use of PDS plates in addition to other materials. They all reported closure rates of at least 80%. The majority of studies reported no postoperative complications. Nasal septal perforation reconstruction with PDS plates is a promising approach that has demonstrated positive outcomes. Further larger studies are required to evaluate the long-term efficacy of using PDS plates on patients with septal perforations.

Critical Quality and Readability Analysis of Online Patient Education Materials on Parotidectomy: A Cross-Sectional Study.

PURPOSE: Complications related to parotidectomy can cause significant morbidity, and thus, the decision to pursue this surgery needs to be well-informed. Given that information available online plays a critical role in patient education, this study aimed to evaluate the readability and quality of online patient education materials (PEMs) regarding parotidectomy. METHODS: A Google search was performed using the term "parotidectomy" and the first 10 pages of the search were analyzed. Quality and reliability of the online information was assessed using the DISCERN instrument. Flesch-Kincaid Grade Level (FKGL) and Flesch-Reading Ease Score (FRE) were used to evaluate readability. RESULTS: Thirty-five PEMs met the inclusion criteria. The average FRE score was 59.3 and 16 (46%) of the online PEMs had FRE scores below 60 indicating that they were fairly difficult to very difficult to read. The average grade level of the PEMs was above the eighth grade when evaluated with the FKGL. The average DISCERN score was 41.7, which is indicative of fair quality. There were no significant differences between PEMs originating from medical institutions and PEMs originating from other sources in terms of quality or readability. CONCLUSION: Online PEMs on parotidectomy may not be comprehensible to the average individual. This study highlights the need for the development of more appropriate PEMs to inform patients about parotidectomy.

Operating Room Noise and Team Communication during Facial Plastic and Reconstructive Surgery: A Multicenter Study.

Operating room (OR) noise contributes to team miscommunication. In facial plastic and reconstructive surgery (FPRS), many cases are completed under sedation. This creates a unique environment wherein patients are aware of OR noise. The objectives of this study were to quantify noise and evaluate team members' perspectives on communication inside of FPRS ORs. This study was completed across three surgical institutions. Objective noise measurements were recorded with SoundMeter X. A communication questionnaire was delivered to OR team members following each case. Four hundred and twenty-three noise measurements were recorded during facelift/neck, eye/brow, rhinoplasty, and fat transfer/lip surgeries. The mean and maximum noise levels were 66.1 dB (dB) and 87.6 dB, respectively. Measurements during cases with general anesthetic (221/423, 52.2%) had higher noise measurements (70.3 dB) compared with those with sedation (202/423, 47.8%) (69.7 dB) (p = 0.04). The OR was louder with suction on (72.3 dB) versus off (69.3 dB) (p <0.00). Suction (34.5%) and music (22.4%) were the largest noise contributors according to questionnaire replies. Intraoperative noise, awake patients, and suctions/music may negatively impact FPRS OR communication. Innovation to improve FPRS intraoperative communication should be considered for effective patient care.

A national strategy to engage medical students in otolaryngology-head and neck surgery medical education: the LearnENT ambassador program.

BACKGROUND: In the realm of medical education, student-led ambassador programs represent an innovative approach to increase awareness about medical education resources. LearnENT is an internationally recognized otolaryngology-head and neck surgery (OHNS) smartphone app and website designed for medical trainees to learn about OHNS. However, upon the initial launch of the app, there was a lack of medical student awareness and engagement. APPROACH: In this article, we highlight the process and lessons learned from developing an ambassador program to increase the national presence and uptake of LearnENT. Medical students from across Canada were recruited and trained to promote the app at their respective institutions. EVALUATION: Ambassadors hosted events and spearheaded initiatives around the country with the goal of showcasing LearnENT. Furthermore, ambassadors were engaged in scholarly initiatives such as creating educational content for LearnENT and giving presentations at national conferences. REFLECTIONS: Critical factors in the success of a student-led ambassador program include ensuring widespread dissemination of the program, establishing clear expectations for ambassadors, equipping ambassadors with standardized promotional material, and promoting collaboration to collectively work towards addressing challenges. When creating a national student-led group such as an ambassador program, outreach to senior stakeholders can be an effective way to involve students at different institutions, provide mentorship opportunities for students and provide opportunities for educational scholarship. With new medical education innovations constantly surfacing, the LearnENT ambassador program model can be applied in other contexts to increase awareness of medical education resources.

Clinical Prediction Models for Suspected Pediatric Foreign Body Aspiration: A Systematic Review and Meta-analysis.

Importance: Although various clinical prediction models (CPMs) have been described for diagnosing pediatric foreign body aspiration (FBA), to our knowledge, there is still no consensus regarding indications for bronchoscopy, the criterion standard for identifying airway foreign bodies. Objective: To evaluate currently available CPMs for diagnosing FBA in children. Data Sources: Performed in Ovid MEDLINE, Ovid Embase, PubMed, Web of Science, and CINAHL database with citation searching of retrieved studies. Study Selection: Prediction model derivation and validation studies for diagnosing FBA in children were included. Exclusion criteria included adult studies; studies that included variables that were not available in routine clinical practice and outcomes for FBA were not separate or extractable. Data Extraction and Synthesis: We followed the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies and the Prediction Model Risk of Bias Assessment Tool framework. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was the diagnosis of FBA as confirmed by bronchoscopy. Characteristics of CPMs and individual predictors were evaluated. The final model presentation with available measures of performance was provided by narrative synthesis. A meta-analysis of individual predictor variables and prediction models was performed. Results: After screening 4233 articles, 7 studies (0.2%; 1577 patients) were included in the final analysis. There were 6 model derivation studies and 1 validation study. Air trapping (odds ratio [OR], 8.3; 95% CI, 4.4-15.5), unilateral reduced air entry (OR, 4.8; 95% CI, 3.5-6.5), witnessed choking (OR, 3.1; 95% CI, 1.0-9.6), wheezing (OR, 2.5; 95% CI, 1.2-5.2), and suspicious findings suggestive of FBA on radiography (OR, 18.5; 95% CI, 5.0-67.7) were the most commonly used predictor variables. Model performance varied, with discrimination scores (C statistic) ranging from 0.74 to 0.88. The pooled weighted C statistic score of all models was 0.86 (95% CI, 0.80-0.92). All studies were deemed to be at high risk of bias, with overfitting of models and lack of validation as the most pertinent concerns. Conclusions and Relevance: This systematic review and meta-analysis suggests that existing CPMs for FBA in children are at a high risk of bias and have not been adequately validated. No current models can be recommended to guide clinical decision-making. Future CPM studies that adhere to recognized standards for development and validation are required.

Published randomized controlled trials of surveillance in cancer patients - a systematic review.

With solid tumor cancer survivorship increasing, the number of patients requiring post-treatment surveillance also continues to increase. This highlights the need for evidence-based cancer surveillance guidelines. Ideally, these guidelines would be based on combined high-quality data from randomized controlled trials (RCTs). We present a systematic review of published cancer surveillance RCTs in which we sought to determine the feasibility of data pooling for guideline development. We carried out a systematic search of medical databases for RCTs in which adult patients with solid tumors that had undergone surgical resection with curative intent and had no metastatic disease at presentation, were randomized to different surveillance regimens that assessed effectiveness on overall survival (OS). We extracted study characteristics and primary and secondary outcomes, and assessed risk of bias and validity of evidence with standardized checklist tools. Our search yielded 32,216 articles for review and 18 distinct RCTs were included in the systematic review. The 18 trials resulted in 23 comparisons of surveillance regimens. There was a highlevel of variation between RCTs, including the study populations evaluated, interventions assessed and follow-up periods for the primary outcome. Most studies evaluated colorectal cancer patients (11/18, [61%]). The risk of bias and validity of evidence were variable and inconsistent across studies. This review demonstrated that there is tremendous heterogeneity among RCTs that evaluate effectiveness of different postoperative surveillance regimens in cancer patients, rendering the consolidation of data to inform high-quality cancer surveillance guidelines unfeasible. Future RCTs in the field should focus on consistent methodology and primary outcome definition.