Citations

AbstractIntroduction/AimsMany people living with amyotrophic lateral sclerosis (PALS) report restrictions in their day‐to‐day communication (communicative participation). However, little is known about which speech features contribute to these restrictions. This study evaluated the effects of common speech symptoms in PALS (reduced overall speaking rate, slowed articulation rate, and increased pausing) on communicative participation restrictions.MethodsParticipants completed surveys (the Communicative Participation Item Bank‐short form; the self‐entry version of the ALS Functional Rating Scale‐Revised) and recorded themselves reading the Bamboo Passage aloud using a smartphone app. Rate and pause measures were extracted from the recordings. The association of various demographic, clinical, self‐reported, and acoustic speech features with communicative participation was evaluated with bivariate correlations. The contribution of salient rate and pause measures to communicative participation was assessed using multiple linear regression.ResultsFifty seven people living with ALS participated in the study (mean age = 61.1 years). Acoustic and self‐report measures of speech and bulbar function were moderately to highly associated with communicative participation (Spearman rho coefficients ranged from rs = 0.48 to rs = 0.77). A regression model including participant age, sex, articulation rate, and percent pause time accounted for 57% of the variance of communicative participation ratings.DiscussionEven though PALS with slowed articulation rate and increased pausing may convey their message clearly, these speech features predict communicative participation restrictions. The identification of quantitative speech features, such as articulation rate and percent pause time, is critical to facilitating early and targeted intervention and for monitoring bulbar decline in ALS.

Abstract Background The extravascular implantable cardioverter defibrillator (EV ICD) has recently emerged as a new option for guideline indicated ICD patients. Previous study results from the EV ICD Pilot and Pivotal studies have demonstrated that the device can provide safe and effective therapy through chronic follow up. However, less has been reported regarding EV ICD lead removal. Purpose To report on the experience of lead removal in the EV ICD Pivotal Study. Methods The EV ICD Pivotal study was an international, prospective, single-arm, premarket clinical study. Patients with a class I or IIa indication for a single-chamber ICD per ESC or ACC/AHA/HRS guidelines were enrolled. Lead removal summary data was reported. Results Of 316 patients with an implant attempt, (74.7% male, age 53.8±13.1 years, 82% primary prevention, LVEF of 38.9%±15.4%, and NYHA Class I [23.7%] or II/III [65.5%]) 299 were fully implanted; 17 (5.7%) of which had a lead removal procedure (14–752 days post-implant, at 13 sites) with 3 of them having been implanted for more than 1 year. Reasons for lead removal were lead dislodgement (n=7), infection (n=5), high impedance alert due to lead fracture (n=2), pacing indication (n=1), cardiac transplant (n=1), or scheduled sternotomy (n=1). New EV ICD leads were placed in 7/17 (41.2%) patients. No serious adverse events were adjudicated as related to the explant procedures. There was a single observation of incision site haemorrhage, that was resolved with wound care. Additional details on lead removal will be included at the time of presentation. Conclusions The EV ICD lead was successfully removed 14-752 days post implant. Nine patients were re-implanted with either extravascular or transvenous systems. Longer term extraction data collection is ongoing through the EV ICD Pivotal study and through the EV ICD post-approval study and will continue to provide additional insights.Lead removed 24 months post-implant.

INTRODUCTION: Since the early 20th century, surgical practices on prophylactic oophorectomy at the time of hysterectomy have fluctuated. This study aims to assess how current gynecologic surgeons are counseling patients on ovary-sparing benign hysterectomies and assess any gaps in provider knowledge. METHODS: Institutional review board exception was obtained. A survey was piloted and underwent several rounds of editing before being sent to members of American Association of Gynecologic Laparoscopists (AAGL) in April 2023. The questionnaire evaluated preoperative counseling on risks and benefits of ovary-sparing hysterectomy for benign indications and surgical practices for when to perform bilateral salpingectomy and oophorectomy. Descriptive statistics and regression analyses were performed. RESULTS: The survey was sent out by email to 6,622 AAGL members, 3,576 opened the email, and 520 completed surveys (14% response rate). Approximately one-half (58%) completed subspeciality training. Most counsel patients on the benefits of ovarian conservation including the prevention of osteoporosis (88%), early onset menopause (87%), cardiovascular disease (84%), and dementia (52%). Fifty percent recommend routine bilateral salpingo-oophorectomy at time of hysterectomy starting at age 61, whereas 38% recommend this be performed at age 51–55 years. CONCLUSION: Gynecologic surgeons are counseling patients on the risks and benefits of ovarian conservation. How frequently ovary-sparing hysterectomies are offered and the age at which bilateral salpingo-oophorectomy is recommended vary by provider. Additional high-quality studies are needed to further understand the optimal timing of oophorectomy at time of benign hysterectomy, and there is also a need for provider education to minimize discrepancy in practice patterns.

Abstract Confounding results of engineered mesenchymal stem cells (MSCs) used as cellular vehicles has plagued technologies whereby success or failure of novel approaches may be dismissed or inaccurately ascribed solely to the biotechnology platform rather than suitability of the human donor. Polymeric materials were screened for non‐viral engineering of MSCs from multiple human donors to deliver bone morphogenic protein‐4 (BMP4), a protein previously investigated in clinical trials for glioblastoma (GBM) to combat a subpopulation of highly invasive and tumorigenic clones. A “smart technology” that target the migratory and stem‐like nature of GBM will require: (1) a cellular vehicle (MSC) which can scavenge and target residual cells left behind after surgical debulking and deliver; (2) anti‐glioma cargo (BMP4). Multiple MSC donors are safely engineered, though varied in susceptibility to accept BMP4 due to intrinsic characteristics revealed by their molecular signatures. Efficiency is compared via secretion, downstream signaling, differentiation, and anti‐proliferative properties across all donors. In a clinically relevant resection and recurrence model of patient‐derived human GBM, we demonstrate that nanoengineered MSCs are not “donor agnostic” and efficacy is influenced by the inherent suitability of the MSC to the cargo. Therefore, donor profiles hold greater influence in determining downstream outcomes than the technical capabilities of the engineering technology.

Introduction: Differential diagnoses of a pediatric neck mass are extensive, ranging across benign, malignant, congenital and infectious causes. Limited access to imaging in low-resource settings increases the complexity of narrowing this list to appropriately diagnose and treat neck masses. This occasionally allows neck masses to grow unchecked, increasing the morbidity of their presence and eventual excision. The goal of this report is to describe nuances in the diagnosis and treatment of pediatric neck masses in resource-limited settings through a case report of a neck mass in a pediatric patient. Patient presentation: A 10-year-old girl in Harare, Zimbabwe, presented for surgical management of a midline neck mass that appeared 4 years prior to presentation for definitive treatment. A myriad of barriers delayed her care, allowing the mass to grow into her floor of mouth, displacing her tongue and leading to speech and feeding difficulties. Management and outcome: At presentation to the tertiary care facility, she received a pre-operative ultrasound showing a well-circumscribed, echogenic mass. Her neck mass was surgically excised through a transoral approach. Permanent pathology was consistent with a dermoid cyst. Conclusion: At 1-month postoperative follow-up, the patient had experienced no complications and had a complete resolution of her functional symptoms and appearance. Contribution: We present a case that can illuminate the utility of ultrasound in the diagnosis of pediatric neck masses. Additionally, we facilitate an important discussion on transoral versus transcervical approach for midline neck masses with the decision hinging on size, location, surgeon preference and comfort and consideration of cosmesis.

Abstract BACKGROUND: The amplification of genes PDL-1, PDL-2, and JAK2 on chromosome 9p24, known as the PDJ amplicon, has been identified in 15% of triple negative breast cancer (TNBC) and is associated with tumor infiltrating lymphocytes and elevated JAK2 mRNA, suggesting a coordinated inflammatory response in TNBC. Adding pembrolizumab to chemotherapy in KEYNOTE trials 355 and 522 has validated the use of PD-1 blockade in TNBC and redefined the standard of care. Despite preclinical data suggesting a role for targeting the IL- 6/JAK2/STAT3 pathway, the JAK1/JAK2 inhibitor ruxolitinib has not shown efficacy as a single Agent in breast cancer. This is the first phase I clinical trial evaluating the combination of pembrolizumab and ruxolitinib in the treatment of metastatic TNBC. METHODS: We conducted a phase I clinical trial with accrual from 2018 to 2023 at Mayo Clinic Arizona. Patients (n=12) received 200 mg of IV pembrolizumab per cycle (every 3 weeks) with 3+3 dose escalation of oral ruxolitinib twice a day (dose level 0: 10 mg PO BID, level 1: 15 mg PO BID, level 2: 20 mg PO BID). The primary endpoint was to determine the maximum tolerated dose (MTD) of ruxolitinib and secondary endpoints were treatment safety and efficacy. Clinical response was assessed by computed tomography of the chest, abdomen, and pelvis every 3 cycles. PD-L1 expression in tumor was measured by immunohistochemistry (IHC). The effect of the combined therapies on T and B cell populations were assessed by flow cytometry and antibody profiling of 695 tumor antigens and 8 viral antigens by nucleic acid protein programmable array. RESULTS: Twelve female patients with chemotherapy refractory metastatic TNBC were treated on study. All received 200 mg IV pembrolizumab every cycle. Due to rapid disease progression of three patients early after treatment initiation, eligibility was restricted to prohibit patients with extensive pulmonary disease or elevated LDH. Those patients were excluded from efficacy or correlative analysis. The most common toxicities were transaminitis (n=12), anemia/leukopenia (n=12), and fatigue (n=9). The majority of adverse events were grade 1 and occurred at dose level 2. There were 5 adverse events grade 3 or higher: respiratory or thoracic complications (n=3), hypertension (n=1), and abdominal pain (n=1), but MTD was not established. The median number of cycles was 4 for each dose level (range n=2.0-9.0) and the median time to progression was 3 months (range n=1.4-6.3). No patient had tumor response by RECIST v1.1 criteria and there was no association of disease stability with PD-L1 tumor expression by IHC. Circulating antibodies to tumor antigens remained stable, and viral-specific antibodies mildly decreased by month 2 in all patients at dose levels 0 and 1. Of the 7 patients reactive to TRIM21 autoantibodies, 2 patients had a transient increase at 2 months. CONCLUSIONS: The combination of pembrolizumab with ruxolitinib was well tolerated at all dose levels, and the number but not the severity of adverse events increased with higher ruxolitinib dose. Two of six patients in dose level 0 and 1 had stable disease for six months on treatment, suggesting that the lower dose levels of ruxolitinib (i.e. 10 mg PO BID) may have more activity in combination with pembrolizumab. Citation Format: Anelia Kassi, Jacqueline Carmona, Sarah M. Green, Heidi Kosiorek, Michael T. Barrett, Barbara A. Pockaj, Donald Northfelt, Karen S. Anderson. Phase I trial of combination pembrolizumab and ruxolitinib in metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-07.

Abstract Background: The three delays model, identifies three key stages to delays in care that can contribute to adverse outcomes: decision-making to seek care, accessing healthcare facilities, and receiving appropriate medical care. However, the application of this model in otolaryngology-head and neck surgery (OHNS) and in a human conflict environment has not been examined. This study aims to explore the impact of each delay type within the OHNS population in post-war Mekelle, Ethiopia. By investigating these delays, the study seeks to uncover strategies for reducing delays and improving outcomes in the management of OHNS pathology for this and similar environments. Methods: This study was conducted during a 3-week short term OHNS surgical trip in Mekele, Ethiopia, following a 2 year war. A total of 105 patients attending the OHNS clinic were identified and given verbal interviews and semi-structured questionnaires. The three delays model was applied to analyze the data collected, focusing on the following aspects: 1) decision to seek care, 2) reaching care, and 3) receiving care. Results: A total of 105 patients were included in the analysis, with 100% (105/105) experiencing type 1 delays (decision to seek care), 75% experiencing type 2 delays (75/105) and an additional 77% (77/105) facing type 3 delays (receiving appropriate care after reaching health care facility). More than half of the patients encountered delays in all three types. Various factors contributed to type 3 delays, including multiple delays at the time of admission, drug shortages, non-availability of skilled staff, and incompetence. Cost of transportation emerged as the primary factor contributing to type 2 delays. Conclusion: The findings provide valuable insights into the specific delays experienced by patients seeking OHNS services in a post-war setting and inform potential strategies for improving healthcare delivery in similar contexts.

Introduction: Surgically implanted epicardial left ventricular (eLV) lead has been used as an alternative approach when implantation of transvenous LV (tLV) lead in patients requiring cardiac resynchronization therapy (CRT) has failed. Recent literatures noted similarities in clinical response between tLV and eLV-CRT patients. However, comparison between CRT patients with ischemic (ICM) and dilated cardiomyopathy (DCM) is currently lacking in eLV-CRT patients. Hypothesis: We hypothesize that DCM patients respond better to eLV-CRT than ICM patients. Methods: Of 1038 patients who underwent tLV-CRT implantation at UCSD and Mayo Clinics between 2002 and 2013, 44 (Age 63±15, 28M) had failed tLV lead placement and received eLV-CRT. Electronic Medical Records of these patients were reviewed. NYHA class and echocardiograph were assessed before and after successful CRT implantation. Results: Following eLV-CRT implantation, improvements were noted in LVEF (26% vs. 31%, p < 0.01), NYHA class (2.9 vs. 2.3, p < 0.01) and LVESD (57mm vs. 52mm, p = 0.03) in the study cohort. In patients with DCM (n=19), the NYHA class (3.0 vs. 2.3, p = 0.01), LVEF (24% vs. 30%, p = 0.02) and LVESD (57mm vs. 52mm, p = 0.04) had significantly improved following CRT implantation compared to baseline (figures). No statistically significant changes in NYHA class, LVEF and LVESD were observed in patients with ICM (all p > 0.05). Conclusion: In this two-center study, eLV-CRT patients with DCM benefited significantly after CRT, as compared to ICM patients. Although larger scaled studies are needed, eLV-CRT may be considered a viable alternative to tLV-CRT, especially in patients with DCM.