Citations

ObjectiveWe present the outcomes for patients with idiopathic subglottic stenosis (iSGS) following their first carbon dioxide laser wedge excision (LWE) procedure, additionally examining the effect of compliance with adjuvant medical therapy (triple therapy) after the operation.Study DesignRetrospective chart review.SettingTertiary center.MethodsA retrospective review was performed on 183 patients with iSGS following their first LWE and their compliance to adjuvant medical therapy (inhaled corticosteroid, proton pump inhibitor, trimethoprim‐sulfamethoxazole) following the operation, with all reviewed to December 31, 2020. The primary outcome variable was median time to recurrence (MTR). Patients were stratified by whether the LWE was their first operation (LWE primary or secondary), by compliance to triple therapy, and by compliance with trimethoprim‐sulfamethoxazole. Kaplan‐Meier analysis and Cox proportional hazards were used to evaluate the MTR across the stratifications.ResultsAn overall 113 patients underwent their first LWE, while 70 received the procedure after having undergone 1 to 13 procedures. The MTR between LWE primary and secondary was 4.6 and 2.9 years, respectively. Adjusted Cox proportional hazards comparing these 2 groups revealed the number of prior operations to be a confounding variable. A statistically increased MTR was demonstrated with greater degrees of medical compliance.ConclusionLWE conferred an MTR of 4.1 years in the iSGS cohort. The number of prior procedures preceding LWE behaved as a confounding variable. Patients who were completely or partially compliant to triple therapy appear to demonstrate increased intervals prior to recurrence.

Abstract Patients with metastatic breast cancer (MBC) typically have short survival times and their successful treatment represents one of most challenging aspects of patient care. This poor prognostic behavior is in part due to molecular features including increased tumor cell clonal heterogeneity, multiple drug resistance mechanisms, and alterations of the tumor microenvironment. The AURORA US Metastasis Project was established with the goal to identify molecular features specifically associated with metastasis. We therefore collected and molecularly characterized specimens from 55 metastatic breast cancer (BC) patients representing 51 primary cancers and 102 metastases. The 153 unique tumors were assayed using RNAseq, tumor/germline DNA exomes and low pass whole genome sequencing, and global DNA methylation microarrays. We found intrinsic molecular subtype differences between primary tumors and their matched metastases to be rare in triple negative breast cancer (TNBC)/Basal-like subtype tumors. Conversely, tumor subtype changes were relatively frequent in estrogen receptor positive (ER+) cancers where ~30% of Luminal A cases switched to Luminal B or HER2-enriched (HER2E) subtypes. Clonal evolution studies identified changes in expression subtype coincident with DNA clonality shifts, especially involving HER2 amplification and/or the HER2E expression subtype. We further found evidence for ER-mediated downregulation of genes involved in cell-cell adhesion in metastases. Microenvironment differences varied according to tumor subtype where ER+/Luminal metastases had lower fibroblast and endothelial cell content, while TNBC/Basal-like metastases showed a dramatic decrease in B cells and T cells. In 17% of metastatic tumors, we identified DNA hypermethylation and/or focal DNA deletions near HLA-A that were associated with its’ significantly reduced expression, and with lower immune cell infiltrates. We also identified low immune cell features in brain and liver metastases when compared to other metastatic sites, even within the same patient. These findings have direct implications for the treatment of metastatic breast cancer patients with immune- and HER2-targeting therapies and suggest potential novel therapeutic avenues for the improvement of outcomes for some patients with MBC.

AbstractThe Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high‐level field‐wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co‐moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.

Retinoic acid (RA) is used in differentiation therapy to treat a variety of cancers including neuroblastoma. The basis for its therapeutic efficacy is unknown, however, mitochondria (MT) have been implicated as key effectors in RA‐mediated differentiation process. Here we use the SH‐SY5Y human neuroblastoma cell line as a model to examine the contribution of MT to the physiological effects of RA treatment. We find that RA induces a dramatic increase in the energy metabolism of SH‐SY5Y cells, and shifts the dependence on energy production from glycolysis to oxidative phosphorylation. RA treatment does not increase the number of MT or cause measurable changes in the composition of the electron transport chain. Rather, RA treatment elevates the production of intracellular pyruvate as fuel for mitochondrial consumption, and significantly enhances the mitochondrial respiratory capacity. We propose a competition model for the therapeutic effects of RA. Specifically, the high metabolic rate in differentiated cells limits the availability of metabolic nutrients for use by the undifferentiated cells and suppresses their growth. Thus, RA treatment provides a selective advantage for the differentiated state.

Objective: Transoral endoscopic laser-assisted diverticulotomy (TELD) with diverticulectomy and diverticuloplasty (TELD + DD) for the management of Zenker’s diverticulum (ZD) has been utilized by our institution since 2016 in attempts to reduce residual pouch size. This technique involves complete endoscopic pouch excision with partial advancement of mucosal flaps. Our study compares the subjective outcomes, objective outcomes, and complication rates between TELD and TELD + DD. Methods: A retrospective cohort study was performed on patients who underwent TELD or TELD + DD by a single surgeon at a tertiary academic center (2013-2019). Videofluoroscopic swallow studies (VFSS) with esophagram, Eating Assessment Tool (EAT-10), Reflux Symptom Index (RSI), and Functional Outcome Swallowing Scale (FOSS) were collected at preoperative and 3 month follow-up visits. A single blinded reviewer recorded height, width, and depth of pre and postoperative pouches with volumetric analysis performed assuming an ellipsoid shape. Comorbidities, complications, postoperative course, and recurrence were recorded. Results: Of the 75 patients that met criteria, 27 underwent TELD + DD and 48 underwent TELD. Eighteen TELD + DD and 37 TELD had both pre and post-operative VFSS. TELD + DD and TELD had a 96 ± 7% and 87 ± 16% reduction in pouch volume, respectively ( t-test; P = .01). Complications (TELD + DD 7%, TELD 17%, fisher’s exact; P = .31) and final subjective outcomes after adjusting for initial were not significantly different between methods (EAT-10 with TELD + DD ∆ + 1.3, P = .18; RSI ∆ + 1.4, P = .29; FOSS ∆-0.02, P = .91). One short-term recurrence was reported with TELD. Conclusion: Use of TELD + DD is associated with a statistically significantly decreased residual pouch size with no significant difference in short-term subjective outcomes. Complication rates and short-term recurrence rates are comparable. Long-term recurrence rates will require further studies to characterize. Level of Evidence: Level 3.

AbstractObjectives/HypothesisTest a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice.Study DesignAnimal model.MethodsLeft recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross‐linked jellyfish collagen (MX‐JC) and adipose derived stem cells (ADSCs), Group 2, MX‐JC alone, Group 3, cross‐linked hyaluronic acid (X‐HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology.ResultsAfter 100 μL IL MRI volumes (means ± STD) at 4 and 12 weeks were: Group 1: 27.2 ± 15.6 and 13.1 ± 5.2 μL, Group 2: 60.8 ± 18 and 27.8 ± 2.47 μL, Group 3: 27.4 ± 12 and 10.6 ± 8 μL, and Group 4: 37.5 ± 11 and 9.85 ± 1 μL. Group 2 volumes were largest and Group 3 were smallest in all comparisons (P < .05). Histologically, low grade inflammatory responses were observed in Group 1, mild histiocytic infiltration in Group 2, widespread muscle fiber loss in Group 3, and plasmocytic infiltration in Group 4.ConclusionsMX‐JC showed the least resorption at 4 and 12 weeks among all groups. T cell inflammatory responses were observed with MX‐JC but were reduced by 12 weeks while B cell immune responses, indicative of antibody priming, were predominantly noted with MACD. MX‐JC + ADSC showed low grade immunity while the XHA showed greater myocyte loss compared to the other groups.Level of EvidenceNA Laryngoscope, 131:E2452–E2460, 2021

ObjectiveInclusion body myositis (IBM) is a progressive inflammatory myopathy with dysphagia as a debilitating sequalae. Otolaryngologists are consulted for surgical candidacy when there are findings of cricopharyngeal dysfunction. We aim to compare transcervical cricopharyngeal myotomy (TCPM) versus endoscopic cricopharyngeal myotomy (ECPM) in the IBM population with particular focus on objective swallow study outcomes, complications, and recurrence rates.MethodsA retrospective cohort study was performed on IBM patients who underwent TCPM or ECPM (1981–2020) in the Department of Otolaryngology at a tertiary academic center with a high volume IBM referral base. Videofluoroscopic swallow studies, Eating Assessment Tool (EAT‐10), Reflux Symptom Index (RSI), and Functional Outcome Swallowing Scale (FOSS) were collected at preoperative and follow‐up visits. Baseline patient characteristics, intraoperative data, and postoperative course were recorded.ResultsForty‐one patients were identified (18 TCPM; 23 ECPM). There was no significant difference in the recurrence rates, complications, hospitalization length, operative time, or return to preoperative diet between approaches. For the 12 patients (11 ECPM; 1 TCPM) that had subjective swallow data, there was a statistically significant difference in the pre and postoperative scores for EAT‐10, RSI, and FOSS (P < .05). There was a statistically significant improvement in the degree of narrowing between pre and postoperative imaging for both approaches (P < .05).ConclusionBoth TCPM and ECPM are safe approaches for the management of dysphagia in patients with IBM with objective evidence of cricopharyngeal dysfunction. Cricopharyngeal myotomy is a durable technique that has demonstrated improved subjective and objective outcomes in this patient population.Level of Evidence3 Laryngoscope, 131:E2426–E2431, 2021