Post-operative evaluation of computed tomography imaging following cochlear implantation.

PURPOSE: This study utilized an automated segmentation algorithm to assess the cochlear implant electrode array within the cochlea and investigate its impact on audiologic outcomes as measured by post-operative speech perception scores. Furthermore, manual evaluations of electrode placement were compared to automatic segmentation methods to determine their accuracy in predicting post-operative audiologic outcomes. MATERIALS AND METHODS: This retrospective chart review was conducted at a tertiary care referral center involving adult post-lingually deafened cochlear implant recipients implanted from 2015 to 2019. Patients with appropriate postoperative imaging and speech testing were included. Patients were excluded if non-English speaking, had a cognitive deficit, or a labyrinthine malformation. Automated and manual methods were used to analyze computed tomography (CT) scans and correlate the findings with post-operative speech perception scores and detection of electrode translocation. RESULTS: Among the 47 patients who met inclusion criteria, 15 had electrode translocations confirmed by automatic segmentation methods. Controlling for CI usage and pre-operative AzBio scores, patients with translocation exhibited significantly lower consonant-nucleus consonant (CNC) and AzBio scores at 6-months post-implantation compared to patients with ST insertions. Moreover, the number of translocated electrode contacts was significantly associated with post-operative CNC scores. Manual evaluations of electrode location were predictive but less sensitive to electrode translocations when compared with automated 3D segmentation. CONCLUSIONS: Placement of CI electrode contacts within ST without translocation into SV, leads to improved audiologic outcomes. Manual assessment of electrode placement via temporal bone CT, without 3D reconstruction, provides a less sensitive method to determine electrode placement than automated methods. LEVEL OF EVIDENCE: Level 4. LAY SUMMARY: This study investigated the impact of electrode placement on speech outcomes for cochlear implant recipients. Using advanced imaging techniques, the researchers compared automated and manual methods for evaluating electrode position and examined the relationship between electrode translocation and audiologic outcomes. The findings revealed that proper placement within the cochlea without translocation into inappropriate compartments inside the cochlea improves speech understanding. Manual evaluations were somewhat accurate but less sensitive in detecting translocations compared to automated methods, which offer more precise predictions of patient outcomes. These results contribute to our understanding of factors influencing cochlear implant success and highlight the importance of optimizing electrode placement for improved speech outcomes.

Impact of an Ultrasound Demonstration on Vascular Surgery Interest in Preclinical Medical Students.

BACKGROUND: One strategy to address the impending shortage of vascular surgeons is to augment interest in the trainee pipeline. Endovascular procedures are unique to vascular surgery (VS) and endovascular simulations have proven effective at generating VS interest in the past. Like endovascular techniques, the use of ultrasound (US) testing in VS is unique among medical specialties. We hypothesized that an interactive US demonstration would increase VS interest in preclinical medical students. METHODS: We created a 5-point Likert scale survey assessing interest in VS, understanding of VS, likelihood to further investigate VS, choosing VS as a rotational elective, and pursuing VS shadowing and research opportunities. This survey was administered 1 day before and 1 day after the demonstration. Results were compared via paired t-test. A VS attending assisted by a senior registered vascular technologist covered physics, B-mode, continuous, pulsed wave, and color Doppler in an interactive, hands-on experience. Our dedicated US simulation laboratory enabled simultaneous interactive virtual broadcast and in-person learning. All first-year and second-year students at our medical school were invited via e-mail. RESULTS: Five hundred twelve students were invited, 39 attended, and 19 students who completed surveys were included. Sixty eight percent were female. Attendance at the US demonstration resulted in a significant increase in students' interest in vascular surgery (P = 0.012), understanding of vascular surgery (P < 0.001), likelihood to further investigate vascular surgery (P < 0.001), likelihood to choose a vascular surgery rotation (P < 0.001), and likelihood to pursue vascular surgery shadowing and research opportunities (P < 0.001). Although only 2 of 6 in-person attendees returned surveys, their increase in average response to all questions was higher than virtual attendees (+1.80 vs. +0.91, P = 0.043). CONCLUSIONS: Attending an interactive US demonstration significantly increased preclinical medical students' interest in understanding of VS. In-person and virtual attendance both had a positive impact. Such a demonstration may be an effective tool to recruit students. It is imperative that we continue innovating to address the future shortage of vascular surgeons.

Predictive value of difficult airway identifiers for intubation-related complications in the emergency department.

OBJECTIVES: The Airway Alert banner at our institution alerts physicians to patients with the potential for a difficult intubation. Difficult airway guidelines can reduce intubation complications in the operating room, but little research has been done in the emergency department (ED). We hypothesize that patients meeting criteria for the banner will have a more difficult intubation and increased complications. METHODS: Patients greater than 18 years old who presented to the ED for any complaint and required intubation were reviewed from January 2015 to January 2020 and divided into those meeting criteria for a difficult airway ("criteria cohort") and those who did not ("non-criteria cohort"). Past medical history and details of the intubation were collected. RESULTS: The mean number of attempts for intubation was 1.60 in the criteria cohort and 1.36 in the non-criteria cohort (P > .05). The mean grade of view was 1.73 and 1.39, respectively (P < .05). The average size of endotracheal tube was 7.50 and 7.74 in the criteria and non-criteria cohorts (P < .05). The use of adjuncts was 28.6% and 12.5%, respectively (P < .01). The average number of intubation attempts and complication rate did not differ significantly. CONCLUSIONS: Intubations in patients meeting criteria for the banner are associated with a more difficult view, use of smaller endotracheal tube, and increased use of adjuncts, but not with a significantly higher rate of complications or attempts. Physicians should prepare with additional endotracheal tube sizes, adjuncts, and a plan for secondary strategies in these patients. LEVEL OF EVIDENCE: 2b.

Mutations associated with a 17-gene leukemia stem cell score and the score's prognostic relevance in the context of the European LeukemiaNet classification of acute myeloid leukemia.

Leukemia stem cells (LSC) are more resistant to standard chemotherapy and their persistence during remission can cause relapse, which is still one of the major clinical challenges in the treatment of acute myeloid leukemia (AML). A better understanding of the mutational patterns and the prognostic impact of molecular markers associated with stemness could lead to better clinical management and improve patients' outcomes. We applied a previously described 17-gene expression score comprising genes differently expressed between LSC and leukemic bulk blasts, for 934 adult patients with de novo AML, and studied associations of the 17-gene LSC score with clinical data and mutation status of 81 genes recurrently mutated in cancer and leukemia. We found that patients with a high 17-gene score were older and had more mutations. The 17-gene score was found to have a prognostic impact in both younger (aged <60 years) and older (aged ≥60 years) patients with AML. We also analyzed the 17-gene LSC score in the context of the 2017 European LeukemiaNet genetic-risk classification and found that for younger patients the score refined the classification, and identified patients currently classified in the European LeukemiaNet Favorable-risk category who had a worse outcome.

EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia.

PURPOSE: EGF-like domain 7 (EGFL7) is a secreted protein and recently has been shown to play an important role in acute myeloid leukemia (AML); however, the underlying mechanism by which EGFL7 promotes leukemogenesis is largely unknown. EXPERIMENTAL DESIGN: Using an antibody interaction array, we measured the ability of EGFL7 to bind directly approximately 400 proteins expressed by primary AML blasts. Primary patient samples were stimulated in vitro with recombinant EGFL7 (rEGFL7) or anti-EGFL7 blocking antibody to assess alterations in downstream signaling and the ability to effect blast differentiation and survival. We treated three independent AML models with anti-EGFL7 or IgG1 control to determine whether anti-EGFL7 could prolong survival in vivo. RESULTS: We found EGFL7 significantly binds several signaling proteins important for normal and malignant hematopoiesis including NOTCH. Stimulation of AML blasts with rEGFL7 reduced NOTCH intracellular domain and NOTCH target gene expression while treatment with an anti-EGFL7 blocking antibody resulted in reactivation of NOTCH signaling, increased differentiation, and apoptosis. Competitive ligand-binding assays showed rEGFL7 inhibits DELTA-like (DLL) 4-mediated NOTCH activation while anti-EGFL7 combined with DLL4 significantly increased NOTCH activation and induced apoptosis. Using three different AML mouse models, we demonstrated that in vivo treatment with anti-EGFL7 alone results in increased survival. CONCLUSIONS: Our data demonstrate that EGFL7 contributes to NOTCH silencing in AML by antagonizing canonical NOTCH ligand binding. Reactivation of NOTCH signaling in vivo using anti-EGFL7 results in prolonged survival of leukemic mice, supporting the use of EGFL7 as a novel therapeutic target in AML.

Percutaneous treatment of ranulas: ultrasound-guided drainage with salivary gland chemical ablation.

BACKGROUND: Ranulas are salivary pseudocysts in the floor of the mouth adjacent to damaged salivary glands. Current surgical management is drainage of the ranula with removal of the offending gland. An analogous percutaneous procedure could potentially offer similar treatment efficacy in a more minimally invasive way. OBJECTIVE: To evaluate the outcomes of a cohort of patients with ranulas treated with percutaneous ranula aspiration and chemical ablation of the source salivary gland to see whether this technique could be proposed as a minimally invasive treatment alternative. MATERIALS AND METHODS: This retrospective single-center study evaluated 24 patients treated percutaneously for ranulas between January 2004 and December 2014. All patients were treated with percutaneous ranula aspiration and chemical ablation of the offending salivary gland. Treatment success and any complications were recorded. RESULTS: Complete ranula eradication was successfully accomplished in 87.5% of the patients with no complications. CONCLUSION: Initial results suggest that our technique of percutaneous aspiration of ranulas and chemical ablation of the source salivary gland is safe and effective.

Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells.

In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged <60 years) 76 older (≥60 years) adults with cytogenetically normal AML with a 'core enriched' (CE) gene expression signature (GES) associated with LSCs. We identified a LSC-specific signature of 111 lncRNAs that correlated strongly with the CE-GES. Among the top upregulated LSC-associated lncRNAs, we identified the lncRNA DANCR. Further experiments confirmed that DANCR is upregulated in functionally validated LSC-enriched populations. DANCR knock-down in LSCs resulted in decreased stem-cell renewal and quiescence. Furthermore, we showed that targeting Dancr in vivo using a primary murine model of AML (expressing both Mll partial tandem duplication/Flt3 internal tandem duplication) prolonged the survival of mice after serial transplantation. Our data suggest that LSCs have a distinct lncRNA signature with functional relevance and therapeutic potential.