Clinical Outcomes in Patients With Krukenberg Tumors From Colorectal Cancer.

INTRODUCTION: Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to diagnostic uncertainty, decreased responsiveness to systemic therapies compared to other sites of metastasis, and associated debilitating symptomatology. Thus, we sought to characterize our institutional outcomes in metastatic colorectal cancer (mCRC) patients with KTs. METHODS: A retrospective single-institution study was performed identifying adult, female patients from 2012 to 2021 with a diagnosis of mCRC. Patient demographics and clinicopathologic characteristics were collected and analyzed. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival analyses were performed. RESULTS: Of 235 mCRC patients, 45 (19.1%) had KTs, 41 (91.1%) of whom had KTs in conjunction with other metastatic sites. Other initial sites of metastasis included the liver (n = 93, 39.6%), lung (n = 28, 11.9%), and peritoneum (n = 18, 7.7%). In the KT cohort, the median age was 48 y, 53.3% were non-Hispanic White, 100% had microsatellite stable tumors, 33.3% had Kristen Rat Sarcoma Virus (KRAS) mutations, and 6.7% had V-raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations. Fifty five point six percent of KT patients underwent cytoreductive surgery (CRS), 24.4% underwent palliative debulking, and 20% underwent no surgical intervention. Reasons for not undergoing CRS were disease-related (n = 14, 70%), due to poor performance status (n = 1, 5%), or both (n = 5, 25%). Five-year overall survival was 48.2% in KT patients who underwent CRS. Poor tumor grade was an independent predictor of mortality (hazard ratio 10.69, 95% confidence interval 1.20-95.47, P = 0.03). CONCLUSIONS: Almost 90% of our patient cohort with KTs from mCRC experience additional sites of metastasis. Around half of KT patients who underwent CRS were alive at 5 y.

Navigating the Potential Energy Surface of CdSe Magic-Sized Clusters: Synthesis and Interconversion of Atomically Precise Nanocrystal Polymorphs.

Magic-sized clusters (MSCs) are kinetically stable, atomically precise intermediates along the quantum dot (QD) reaction potential energy surface. Literature precedent establishes two classes of cadmium selenide MSCs with QD-like inorganic cores: one class is proposed to be cation-rich with a zincblende crystal structure, while the other is proposed to be stoichiometric with a "wurtzite-like" core. However, the wide range of synthetic protocols used to access MSCs has made direct comparisons of their structure and surface chemistry difficult. Furthermore, the physical and chemical relationships between MSC polymorphs are yet to be established. Here, we demonstrate that both cation-rich and stoichiometric CdSe MSCs can be synthesized from identical reagents and can be interconverted through the addition of either excess cadmium or selenium precursor. The structural and compositional differences between these two polymorphs are contrasted using a combination of 1H NMR spectroscopy, X-ray diffraction (XRD), pair distribution function (PDF) analysis, inductively coupled plasma optical emission spectroscopy, and UV-vis transient absorption spectroscopy. The subsequent polymorph interconversion reactions are monitored by UV-vis absorption spectroscopy, with evidence for an altered cluster atomic structure observed by powder XRD and PDF analysis. This work helps to simplify the complex picture of the CdSe nanocrystal landscape and provides a method to explore structure-property relationships in colloidal semiconductors through atomically precise synthesis.

Stakeholders' perception on the implementation of Developmental Progress Assessment: using the Theoretical Domains Framework to document behavioral determinants.

BACKGROUND: The widespread implementation of longitudinal assessment (LA) to document trainees' progression to independent practice rests more on speculative rather than evidence-based benefits. We aimed to document stakeholders' knowledge of- and attitudes towards LA, and identify how the supports and barriers can help or hinder the uptake and sustainable use of LA. METHODS: We interviewed representatives from four stakeholder groups involved in LA. The interview protocols were based on the Theoretical Domains Framework (TDF), which contains a total of 14 behaviour change determinants. Two team members coded the interviews deductively to the TDF, with a third resolving differences in coding. The qualitative data analysis was completed with iterative consultations and discussions with team members until consensus was achieved. Saliency analysis was used to identify dominant domains. RESULTS: Forty-one individuals participated in the study. Three dominant domains were identified. Participants perceive that LA has more positive than negative consequences and requires substantial ressources. All the elements and characteristics of LA are present in our data, with differences between stakeholders. CONCLUSION: Going forward, we could develop and implement tailored and theory driven interventions to promote a shared understanding of LA, and maintain potential positive outcomes while reducing negative ones. Furthermore, ressources to support LA implementation need to be addressed to facilitate its uptake.

Assessing the acceptability of script concordance testing: a nationwide study in otolaryngology.

Background: Script concordance testing (SCT) is an objective method to evaluate clinical reasoning that assesses the ability to interpret medical information under conditions of uncertainty. Many studies have supported its validity as a tool to assess higher levels of learning, but little is known about its acceptability to major stakeholders. The aim of this study was to determine the acceptability of SCT to residents in otolaryngology ­ head and neck surgery (OTL-HNS) and a reference group of experts. Methods: In 2013 and 2016, a set of SCT questions, as well a post-test exit survey, were included in the National In-Training Examination (NITE) for OTL-HNS. This examination is administered to all OTL-HNS residents across Canada who are in the second to fifth year of residency. The same SCT questions and survey were then sent to a group of OTL-HNS surgeons from 4 Canadian universities. Results: For 64.4% of faculty and residents, the study was their first exposure to SCT. Overall, residents found it difficult to adapt to this form of testing, thought that the clinical scenarios were not clear and believed that SCT was not useful for assessing clinical reasoning. In contrast, the vast majority of experts felt that the test questions reflected real-life clinical situations and would recommend SCT as an evaluation method in OTL-HNS. Conclusion: Views about the acceptability of SCT as an assessment tool for clinical reasoning differed between OTL-HNS residents and experts. Education about SCT and increased exposure to this testing method are necessary to improve residents' perceptions of SCT.

Contexte: Le test de concordance de script (TCS) est une méthode objective d'évaluation du raisonnement clinique qui mesure la capacité d'interpréter les renseignements médicaux en contexte d'incertitude. Beaucoup d'études en appuient la validité en tant qu'outil pour évaluer l'enseignement supérieur, mais on en sait peu sur son acceptabilité auprès des principales parties prenantes. Le but de cette étude était de déterminer l'acceptabilité du TCS chez les résidents en otorhinolaryngologie ­ chirurgie de la tête et du cou (ORL ­ chirurgie tête et cou) et un groupe de référence composé d'experts. Méthodes: En 2013 et 2016, une série de questions de TCS, de même qu'un questionnaire post-test, ont été inclus dans l'examen national en cours de formation NITE (National In-Training Examination) pour l'ORL ­ chirurgie tête et cou. Cet examen est administré à tous les résidents en ORL ­ chirurgie tête et cou au Canada qui sont entre leurs deuxième et cinquième années de résidence. Les mêmes questions de TCS ont été envoyées à un groupe de chirurgiens en ORL ­ chirurgie tête et cou de 4 université canadiennes. Résultats: Pour 64,4 % des membres facultaires et des résidents, l'étude était leur première exposition au TCS. Dans l'ensemble, les résidents ont trouvé difficile de s'adapter à cette forme de test, même si les scénarios cliniques étaient clairs, et ils ont estimé que le TCS était peu utile pour évaluer le raisonnement clinique. En revanche, la grande majorité des experts ont jugé que les questions du test reflétaient la réalité des cas cliniques et recommanderaient le TCS comme méthode d'évaluation en ORL ­ chirurgie tête et cou. Conclusion: Entre les résidents et les experts en ORL ­ chirurgie tête et cou, les points de vue quant à l'acceptabilité du TCS comme outil d'évaluation du raisonnement clinique ont différé et il faudrait y exposer les résidents davantage pour améliorer leur perception du TCS.

Daughters' experiences of shared caregiving to a parent with dementia.

BACKGROUND: Siblings often share in the care of parents with dementia, but little is known about how care is shared. Research suggests that in comparison with their brothers, sisters provide the majority of care to a parent with dementia and this can contribute to the sisters experiencing poorer health outcomes. There is limited knowledge about how to guide siblings who share in the care of a parent with dementia. AIM: Our qualitative descriptive study sought to explore the experiences of adult daughters sharing care responsibilities with their siblings. The study protocol was approved by institutional (University of Toronto and Baycrest Health Sciences) research ethics boards. MATERIALS & METHODS: Thirty-four daughters participated in an online qualitative survey. Data were analysed using Braun and Clarke's (Qualitative Research in Psychology, 3, 2006, 77) 6-step process. RESULTS: In an overarching theme, daughters expected shared caregiving with their siblings. They conceptualised this to be a practice of being equitable in dividing care responsibilities and fulfilling a supportive role for a parent with dementia; however, this expectation was not met by most daughters. Two subthemes were identified: (a) factors facilitating/constraining shared caregiving and (b) consequences of sharing care. The findings highlight the importance of understanding shared caregiving among siblings when caring for a parent with dementia. DISCUSSION: Results from this study suggest that although shared caregiving is often the goal, factors such as gender roles, geographical proximity, caregiver expertise/skill set and work schedules affect caregivers' abilities to share caregiving. These factors affected whether daughters viewed the caregiving situation as being shared equitably or inequitably, and this led to feelings of acceptance or resentment of their sibling's contribution to the care of their parent. CONCLUSIONS: Healthcare providers can utilise these findings to better support adult-child caregivers negotiating care with their siblings.

Glutathione limits aquacopper(I) to sub-femtomolar concentrations through cooperative assembly of a tetranuclear cluster.

The tripeptide glutathione (GSH) is a crucial intracellular reductant and radical scavenger, but it may also coordinate the soft Cu(I) cation and thereby yield pro-oxidant species. The GSH-Cu(I) interaction is thus a key consideration for both redox and copper homeostasis in cells. However, even after nearly four decades of investigation, the nature and stability of the GSH-Cu(I) complexes formed under biologically relevant conditions remain controversial. Here, we revealed the unexpected predominance of a tetranuclear [Cu4(GS)6] cluster that is sufficiently stable to limit the effective free aquacopper(I) concentration to the sub-femtomolar regime. Combined spectrophotometric-potentiometric titrations at biologically realistic GSH/Cu(I) ratios, enabled by our recently developed Cu(I) affinity standards and corroborated by low-temperature phosphorescence studies, established cooperative assembly of [Cu4(GS)6] as the dominant species over a wide pH range, from 5.5 to 7.5. Our robust model for the glutathione-Cu(I) equilibrium system sets a firm upper limit on the thermodynamic availability of intracellular copper that is 3 orders of magnitude lower than previously estimated. Taking into account their ability to catalyze the production of deleterious superoxide, the formation of Cu(I)-glutathione complexes might be avoided under normal physiological conditions. The actual intracellular Cu(I) availability may thus be regulated a further 3 orders of magnitude below the GSH/Cu(I) affinity limit, consistent with the most recent affinity determinations of Cu(I) chaperones.

Decreased polycystin 2 expression alters calcium-contraction coupling and changes ß-adrenergic signaling pathways.

Cardiac disorders are the main cause of mortality in autosomal-dominant polycystic kidney disease (ADPKD). However, how mutated polycystins predispose patients with ADPKD to cardiac pathologies before development of renal dysfunction is unknown. We investigate the effect of decreased levels of polycystin 2 (PC2), a calcium channel that interacts with the ryanodine receptor, on myocardial function. We hypothesize that heterozygous PC2 mice (Pkd2(+/-)) undergo cardiac remodeling as a result of changes in calcium handling, separate from renal complications. We found that Pkd2(+/-) cardiomyocytes have altered calcium handling, independent of desensitized calcium-contraction coupling. Paradoxically, in Pkd2(+/-) mice, protein kinase A (PKA) phosphorylation of phospholamban (PLB) was decreased, whereas PKA phosphorylation of troponin I was increased, explaining the decoupling between calcium signaling and contractility. In silico modeling supported this relationship. Echocardiography measurements showed that Pkd2(+/-) mice have increased left ventricular ejection fraction after stimulation with isoproterenol (ISO), a ß-adrenergic receptor (ßAR) agonist. Blockers of ßAR-1 and ßAR-2 inhibited the ISO response in Pkd2(+/-) mice, suggesting that the dephosphorylated state of PLB is primarily by ßAR-2 signaling. Importantly, the Pkd2(+/-) mice were normotensive and had no evidence of renal cysts. Our results showed that decreased PC2 levels shifted the ßAR pathway balance and changed expression of calcium handling proteins, which resulted in altered cardiac contractility. We propose that PC2 levels in the heart may directly contribute to cardiac remodeling in patients with ADPKD in the absence of renal dysfunction.

Cyst formation following disruption of intracellular calcium signaling.

Mutations in polycystin 1 and 2 (PC1 and PC2) cause the common genetic kidney disorder autosomal dominant polycystic kidney disease (ADPKD). It is unknown how these mutations result in renal cysts, but dysregulation of calcium (Ca(2+)) signaling is a known consequence of PC2 mutations. PC2 functions as a Ca(2+)-activated Ca(2+) channel of the endoplasmic reticulum. We hypothesize that Ca(2+) signaling through PC2, or other intracellular Ca(2+) channels such as the inositol 1,4,5-trisphosphate receptor (InsP3R), is necessary to maintain renal epithelial cell function and that disruption of the Ca(2+) signaling leads to renal cyst development. The cell line LLC-PK1 has traditionally been used for studying PKD-causing mutations and Ca(2+) signaling in 2D culture systems. We demonstrate that this cell line can be used in long-term (8 wk) 3D tissue culture systems. In 2D systems, knockdown of InsP3R results in decreased Ca(2+) transient signals that are rescued by overexpression of PC2. In 3D systems, knockdown of either PC2 or InsP3R leads to cyst formation, but knockdown of InsP3R type 1 (InsP3R1) generated the largest cysts. InsP3R1 and InsP3R3 are differentially localized in both mouse and human kidney, suggesting that regional disruption of Ca(2+) signaling contributes to cystogenesis. All cysts had intact cilia 2 wk after starting 3D culture, but the cells with InsP3R1 knockdown lost cilia as the cysts grew. Studies combining 2D and 3D cell culture systems will assist in understanding how mutations in PC2 that confer altered Ca(2+) signaling lead to ADPKD cysts.

Nationwide study of publication misrepresentation in applicants to residency.

OBJECTIVES: This study was conducted to assess the prevalence of research publication misrepresentation amongst Canadian Resident Matching Service (CaRMS) applicants to a single surgical subspecialty residency as a potential means of assessing professional behaviour. METHODS: The authors reviewed CaRMS application forms to Canadian otolaryngology residency programmes over a 3-year period (2006-2008) for peer-reviewed publications reported as 'published', 'accepted' and 'in press'. Citations were verified by searching PubMed, Google Scholar and electronic journals. Misrepresentation was defined as any of: (i) falsely claimed authorship of an existing article; (ii) claimed authorship of a non-existing article, and (iii) improper ordering of authorship. Outcomes included descriptive statistics, as well as sub-analyses pertaining to age, gender, affiliated medical school and academic degree, and number of publications per applicant. RESULTS: A total of 427 peer-reviewed publications were reported by 124 of 182 applicants (68% of applicants reported at least one publication). Of the 385 verifiable publications, 47 (12% of articles) were misrepresented by 29 applicants (23% of applicants claiming publication) self-reporting at least one publication. Age, gender, location of medical training, prior academic degree and number of citations per applicant did not relate to likelihood of misrepresentation (p > 0.05). CONCLUSIONS: This study documents the nationwide prevalence of publication misrepresentation amongst applicants to Canadian otolaryngology residency programmes. The high rate of misrepresentation aligns with data reported in the literature and highlights the need to institute measures to dissuade graduates from this form of unprofessional behaviour.

Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is reduced in obese mice, but metabolic homeostasis is preserved in mice lacking InsP3R-II.

Inositol 1,4,5-trisphosphate receptor type II (InsP3R-II) is the most prevalent isoform of the InsP3R in hepatocytes and is concentrated under the canalicular membrane, where it plays an important role in bile secretion. We hypothesized that altered calcium (Ca(2+)) signaling may be involved in metabolic dysfunction, as InsP3R-mediated Ca(2+) signals have been implicated in the regulation of hepatic glucose homeostasis. Here, we find that InsP3R-II, but not InsP3R-I, is reduced in the livers of obese mice. In our investigation of the functional consequences of InsP3R-II deficiency, we found that organic anion secretion at the canalicular membrane and Ca(2+) signals were impaired. However, mice lacking InsP3R-II showed no deficits in energy balance, glucose production, glucose tolerance, or susceptibility to hepatic steatosis. Thus, our results suggest that reduced InsP3R-II expression is not sufficient to account for any disruptions in metabolic homeostasis that are observed in mouse models of obesity. We conclude that metabolic homeostasis is maintained independently of InsP3R-II. Loss of InsP3R-II does impair secretion of bile components; therefore, we suggest that conditions of obesity would lead to a decrease in this Ca(2+)-sensitive process.

Home sleep apnea tests: Conflicts of interest and funding.

OBJECTIVE: Pediatric otolaryngologists rely on HSAT literature to guide their diagnostic methods related to obstructive sleep apnea (OSA). Our objectives were to review the rates of presence of funding and/or potential conflict of interest (COI), as well as its relationship to the overall quality of HSAT publications in the literature over the last two decades. DATA SOURCES: Medline, Web of Science and Embase databases. REVIEW METHODS: A review was performed reviewing publications from January 2000 to December 2021. Oxford Level of Evidence (OLE) was used as a quality metric. COI and funding were recorded verbatim as self-declared in the text of the manuscript. RESULTS: Literature search yielded 4257 articles with 400 articles included in final analysis. The odds of higher quality studies (LOE 1 or 2) were higher in the last five years from 2016 to 2021 (OR, 3.6; 95% CI 1.4 to 6.9). Nearly half of all articles (43.0%) lacked a statement regarding funding or COI. There was a positive correlation between level of evidence and industry funding. The largest source of funding was from industry, comprising 39.6% of all studies that had a funding statement. Of these industry-funded studies, 37.5% reported no COI or lacked a COI statement. CONCLUSION: Despite a growing interest in HSATs for OSA evaluation, there is heterogeneity in reporting of COI and high prevalence of industry funding and COI. Re-evaluation and consensus amongst journals on guidelines for reporting disclosures are needed.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of Poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers Euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory dsRNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi resistant ovarian tumor growth in vivo, and promotes anti-tumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

Proposed Quality Indicators for Aspects of Pediatric Acute Otitis Media Management.

BACKGROUND: The high incidence of pediatric acute otitis media (AOM) makes the implications of overdiagnosis and overtreatment far-reaching. Quality indicators (QIs) for AOM are limited, drawing from generalized upper respiratory infection QIs, or locally developed benchmarks. Recognizing this, we sought to develop pediatric AOM QIs to build a foundation for future quality improvement efforts. METHODS: Candidate indicators (CIs) were extracted from existing guidelines and position statements. The modified RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness methodology was used to select the final QIs by an 11-member expert panel consisting of otolaryngology-head and neck surgeons, a pediatrician and family physician. RESULTS: Twenty-seven CIs were identified after literature review, with an additional CI developed by the expert panel. After the first round of evaluations, the panel agreed on 4 CIs as appropriate QIs. After an expert panel meeting and subsequent second round of evaluations, the panel agreed on 8 final QIs as appropriate measures of high-quality care. The 8 final QIs focus on topics of antimicrobial management, specialty referral, and tympanostomy tube counseling. CONCLUSIONS: Evidence of variable and substandard care persists in the diagnosis and management of pediatric AOM despite the existence of high-quality guidelines. This study proposes 8 QIs which compliment guideline recommendations and are meant to facilitate future quality improvement initiatives that can improve patient outcomes.

Novel measurements of the length of the subglottic airway in infants and young children.

BACKGROUND: To date, the lengths of the subglottic and tracheal airway segments have been measured from autopsy specimens. Images of the head and neck obtained from computerized tomography (CT) provide an alternate method. Our objective in this study was to identify anatomic landmarks from CT scans in infants and young children to estimate the lengths of the subglottic and tracheal airway segments and to correlate these lengths with age. METHODS: We performed a retrospective analysis of CT images of the neck for various diagnostic indications in children ≤3 years. We obtained planes of reconstruction at the level of the vocal cords (VCs), cricoid cartilage, and carina (C) which were parallel to each other and perpendicular to sagittal long axis of the trachea. The lengths of the subglottic airway (LengthSG) and total length of the laryngotracheal airway (LengthVC-C) were measured from the distance between, respectively, the VC versus cricoid cartilage and the VC versus C planes of reconstruction. Tracheal length was then calculated as the difference between LengthVC-C and LengthSG. RESULTS: Fifty-six children met the inclusion criteria. There were 29 boys. The median weight was 10.7 kg (range 3.1-19.0 kg). Regression analysis yielded mean LengthSG (mm) = 7.8 + 0.03·corrected age (months), r(2) = 0.07, P = 0.056; lower and upper 95% confidence interval for ß = 0.03 were -0.001 and 0061. The mean LengthSG was 8.4 mm with an SD of 1.4 mm. The 95th percentile for LengthSG was 10.8 mm, and the 5% to 95% interquartile range was 4.9 mm. The estimate for the 95% confidence interval of the 95th percentile was between 10.2 and 11.3 mm. The LengthVC-C increased with age: mean LengthVC-C (cm) = 5.3 + 0.05·corrected age (months), r(2) = 0.7, P < 0.001. Tracheal length also increased with age: mean tracheal length (cm) = 4.5 + 0.05·corrected age (months), r(2) = 0.6, P < 0.001. CONCLUSION: We report a novel estimate method for the lengths of the airway segments between the VC and C in 56 infants and young children and suggest that the growth characteristics of the subglottic and tracheal airway may differ.

A Review of the Recent Advances of Cardiac Pacemaker Technology in Handling Complications.

The total number of annual pacemaker implantations continues to grow globally, and help patients with heart rhythm disorders with an improved quality of life and reduced mortality. The first implantable pacemakers appeared in 1965, characterized by their bulkiness, short battery life, and a single pacing mode. Innovation led to the modern pacemaker: a smaller system with improved battery life and capacity, and innovation in lead technology. Certain arrhythmia conditions may also qualify for leadless pacemaker implantation, thus eliminating the spectrum of complications that could occur with leads. Adverse events can be divided into acute (perforation, lead dislodgement, infection) and long-term (lead fractures, device infection, insulation failure). Traditional long-term complications with leads occur in 10% of patients, compared with device-related adverse effects observed in 6.7% of leadless pacemakers. Furthermore, cardiac pacemaker implantation results in quality of life improvements across all age groups. Large cardiac rehabilitation studies have demonstrated the effectiveness of exercise in reducing the physical complications involved with pacemaker implantation. Of the three randomized controlled trials examined, all of them reported some benefit of exercise in the intervention group compared with the control. The following review aims to discuss the multitude of pacemaker options potentially available for the clinician, complications, their course of management, and the path forward with innovations arising out of previous research within the field.

Cholesteatoma in Congenital Aural Atresia and External Auditory Canal Stenosis: A Systematic Review.

OBJECTIVE: Patients with congenital external auditory canal (EAC) abnormalities are at risk of developing cholesteatoma and often undergo surveillance imaging to detect it. The aims of this systematic review are to determine the incidence of cholesteatoma in patients with congenital aural atresia (CAA) and patients with congenital EAC stenosis and to investigate the most common age of cholesteatoma diagnosis. This information will help clinicians decide which patients require surveillance scanning, as well as the timing of imaging. DATA SOURCES: Ovid MEDLINE, Embase, CENTRAL, and Web of Science databases. REVIEW METHODS: A systematic literature review following the PRISMA guidelines was performed. The data sources were searched by 2 independent reviewers, and articles were included that reported on CAA or congenital EAC stenosis with a confirmed diagnosis of cholesteatoma. The selected articles were screened separately by 3 reviewers before reaching a consensus on the final articles to include. Data collection on the number of patients with cholesteatoma and the age of diagnosis was performed for these articles. RESULTS: Eight articles met the inclusion criteria. The incidence of cholesteatoma was 1.7% (4/238) in CAA and 43.0% (203/473) in congenital EAC stenosis. The majority of patients with congenital EAC stenosis that developed cholesteatoma were diagnosed at age <12 years. CONCLUSION: CAA is associated with a low risk of cholesteatoma formation, and surveillance imaging is unnecessary in asymptomatic patients. EAC stenosis is strongly associated with cholesteatoma, and a surveillance scan for these patients is recommended prior to 12 years of age with close follow-up into adulthood.

What is the Current State of Extended Reality Use in Otolaryngology Training? A Scoping Review.

OBJECTIVE: To map current literature on the educational use of extended reality (XR) in Otolaryngology-Head and Neck Surgery (OHNS) to inform teaching and research. STUDY DESIGN: Scoping Review. METHODS: A scoping review was conducted, identifying literature through MEDLINE, Ovid Embase, and Web of Science databases. Findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review checklist. Studies were included if they involved OHNS trainees or medical students who used XR for an educational purpose in OHNS. XR was defined as: fully-immersive virtual reality (VR) using head-mounted displays (HMDs), non-immersive and semi-immersive VR, augmented reality (AR), or mixed reality (MR). Data on device use were extracted, and educational outcomes were analyzed according to Kirkpatrick's evaluation framework. RESULTS: Of the 1,434 unique abstracts identified, 40 articles were included. All articles reported on VR; none discussed AR or MR. Twenty-nine articles were categorized as semi-immersive, none used occlusive HMDs therefore, none met modern definitions of immersive VR. Most studies (29 of 40) targeted temporal bone surgery. Using the Kirkpatrick four-level evaluation model, all studies were limited to level-1 (learner reaction) or level-2 (knowledge or skill performance). CONCLUSIONS: Current educational applications of XR in OHNS are limited to VR, do not fully immerse participants and do not assess higher-level learning outcomes. The educational OHNS community would benefit from a shared definition for VR technology, assessment of skills transfer (level-3 and higher), and deliberate testing of AR, MR, and procedures beyond temporal bone surgery. Laryngoscope, 133:227-234, 2023.