Citations

Abstract RATIONALE: Clinical practice guidelines recommend that mechanically ventilated patients (MVPs) receiving sedative therapy achieve a target goal of ‘awake and calm’ when medically possible. However, ICU sedation practices rely on clinicians’ administration of medications based on observations of patients’ arousal/motor activity that are not consistently based on symptom assessments nor consider patients’ preferences. We hypothesized that MVPs would safely self-manage sedative therapy (SMST) base on individual needs and perceived anxiety while experiencing less sedative exposure and delirium. METHODS: A two-group randomized clinical trial conducted in two Midwestern academic medical centers enrolled 161 MVPs willing and able to depress a medication delivery push-button device who remained on protocol for 7 days or until extubated, withdrew or died. Control group (CG) patients (n=81) received sedative medications administered by ICU nurses per unit protocols. Experimental SMST group patients (n=80) received a basal infusion of dexmedetomidine (0.2 mcg/kg/hr titrated per algorithm) + self-administered bolus doses (0.25 mcg/kg up to 3/hour). Primary outcomes were anxiety ratings using a 100-mm visual analog scale (VAS-A), sedation intensity score (aggregate summary of 9 intravenous sedative/opioid medications received range 0-36), and incidence of delirium using the CAM-ICU. Analyses were descriptive and parametric statistics and Generalized Estimating Equations. RESULTS: Patients were predominantly White (93%) females (55%), mean age 58.9+15.1 years receiving mechanical ventilation for respiratory failure (60%) with mean APACHE III of 84.5 + 32.5. Anxiety was highly variable over time wherein patients in both groups endorsed the full range from 0-100. VAS-A over time between groups was -0.06 (p=0.98) indicating that anxiety was 0.06 units lower for SMST patients versus CG. Median sedation intensity in SMST group 11.8 + 9.6, compared to CG 12.7 + 9.6 (p = 0.55) over 7 days. 10.2% of SMST patients had one or more incident delirium events compared to 8.5% of CG (p =.97). Hypotension was experienced equally between groups: 22 in SMST, 23 in CG (p = 1.0) as were device disruptions: 2 in SMST versus 3 in CG (p = 1.0). 82% of SMST were satisfied/very satisfied with ability to self-administer dexmedetomidine; 70% were satisfied/very satisfied with ability to control anxiety; 68% were satisfied/very satisfied with the level of relaxation experienced. CONCLUSIONS: Although there were no significant differences between groups on the primary outcomes, the experimental SMST intervention was safe with high patient-reported satisfaction. SMST may be a viable new paradigm for sedative therapy administration among select ICU patients.

Abstract Reconstruction of clival defects may be challenging in expanded endonasal skull base surgery. We conducted a systematic review to evaluate the outcomes of vascularized flaps used for clival reconstruction. The following databases were searched using a combination of Medical Subject Headings (MeSH) and keywords related to clival reconstruction in July 2024: Ovid Medline, Ovid Embase, Scopus, and Web of Science. Studies reporting outcomes of clival reconstruction with vascularized free and pedicled flaps in patients were selected for complete review. Twenty-three studies were included for detailed study. Clival reconstruction with free flaps was done in 18 patients; 17 had a successful repair, outcome was not reported for 1. Facial vessels were preferred for microvascular anastomosis. Radial artery forearm flap and anterolateral thigh flap were most utilized. Pedicled flaps were used in 68 patients, with reported success in 85.3%. Nasoseptal flap was the most common intranasal flap, used in 34 patients with successful reconstruction in 85.3%. Temporoparietal fascia flap was the most common extranasal flap, successfully used in 13 patients. Intranasal pedicled flaps, wherever available, were preferably used for primary reconstruction; extranasal flaps were the next choice. Free flaps were reserved for salvage reconstruction due to prior failed or unavailable local pedicled flaps. Satisfactory reconstructive outcomes are reported using pedicled and free flaps. The flap of choice is determined by the previous surgical history, radiotherapy, wound vascularity, defect size, overall health of the surrounding nasal mucosa, simultaneous clival surgery, and the preferred pedicle transposition route (free flaps).

Abstract A hallmark of GBM is its highly-immunosuppressive tumor microenvironment (TME). GBM stem-like cells (GSCs) can evade immune surveillance to allow for continued tumor growth and propagation. GSCs regulate the immune TME through recruitment and production of immunosuppressive cells and factors via tumor cell-intrinsic mechanisms. Blocking these cell-intrinsic immunosuppressive mechanisms is widely viewed as a way to enhance the effects of current immune therapies. We recently showed that TGFβ type II receptor (TGFBR2) promotes a mesenchymal transition in GBM cells characterized by high expression levels of immunosuppressive genes NT5E (CD73), ENTPD1 (CD73), LGALS1 (galectin-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and TGFB1. miRNA network analysis identified miR-16-5p and miR-124-3p as high-confidence candidates to block the expression of these immunosuppressive signaling axis in GBM cells. Transgenic miR-16-5p and miR-124-3p simultaneously reduced expression of CD274, ENTPD1, NT5E, TGFB1, and LGALS1 and increased tumor cell killing of PBMC-derived CD4+ and CD8+ T cells. We also measured an increase in drivers of the CD8+ effector state and a decrease in expression of exhaustion marker PD1 in PBMC-derived CD8+ T cells. In addition to the effects on CD4+ and CD8+ T cell activation and function, miRNA-mediated knock-down of this immunosuppressive gene signature in tumor cells also resulted in a decrease in CD206 expression and reduced release of anti-inflammatory chemokines in THP1 cells. These findings demonstrate that miRNA-based gene inhibition can block cell-intrinsic immunosuppressive pathways to enhance anti-tumor immune cell function in vitro and predicts that delivering these miRNAs using advanced nanocarriers will cooperate with current immunotherapies in vivo. Citation Format: TC Taylor, Amanda Johnson, Harmon Khela, Jack Korleski, Sophie Sall, Bachchu Lal, Karen Smith-Connor, Hernando Lopez-Bertoni. miR-16-5p and miR-124-3p block the immunosuppressive phenotype of GBM cells in vitro. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1357.

Introduction: Despite significant advancements in COVID-19 treatment and prevention, immunocompromised individuals, particularly those with hematological malignancies, remain at high risk for severe infection and suboptimal vaccine response. Pre-exposure prophylaxis strategies for these vulnerable populations have been limited. Monoclonal antibodies, proteins designed to target specific antigens, offer a promising preventive solution for individuals unable to mount a sufficient immune response to vaccination. However, there is a critical unmet need to establish clear patient selection criteria for pre-exposure prophylaxis with monoclonal antibodies in these groups. This consensus statement explores recent research to address this gap, outlining profiles of patients most likely to benefit from monoclonal antibody-based prophylaxis. Methodology: The consensus statement was developed through a rigorous process, utilizing a pre-Delphi search method and a modified Delphi technique to gather expert opinions. This approach ensured a comprehensive and informed consensus among experts in the field. Initially, nine distinct patient categories requiring pre-exposure prophylaxis with monoclonal antibodies were identified. Through iterative rounds of expert feedback, discussion, and refinement, these nine categories were expanded and subdivided into twelve more specific groups of hematological malignancies and immunocompromised disorders. This refinement aimed to better capture the diverse patient profiles requiring prophylaxis, providing a more detailed framework for the targeted administration of monoclonal antibodies. Results: The study resulted in the panel members agreeing on nine categories for the use of monoclonal antibodies in COVID-19 prevention for high-risk patients. Achieving consensus among experts is crucial as it reflects the collective validation of evidence-based recommendations that can be reliably applied in clinical practice. A 100% agreement was reached for HIV and AIDS, underscoring the unanimous recognition of the vulnerability of this group to severe COVID-19 outcomes. Similarly, 96% agreement was reached for patients on immunomodulatory drugs (IMiDs), and 90.5% for those with hematological diseases, highlighting strong expert support for prophylaxis in these categories. Immunodeficiencies and renal conditions garnered 86% agreement, indicating broad, although slightly more varied, expert consensus on these groups. Lastly, 80% of the panel supported patients with solid organ cancer, liver conditions, rare neurological disorders, and severe life-limiting neuro-disabilities, reflecting recognition of their elevated risk despite more diverse opinions for these categories. Conclusion: This consensus statement offers healthcare professionals in the UAE a clear, evidence-based framework for the use of monoclonal antibodies in preventing COVID-19 among patients with hematological malignancies and immunocompromised conditions. By outlining specific patient categories, the statement provides a practical guide that enables clinicians to make informed decisions about pre-exposure prophylaxis, ensuring that high-risk individuals receive timely and appropriate protection. The consensus not only enhances the ability of healthcare providers to identify and prioritize at-risk populations, but also optimizes patient outcomes by streamlining preventive measures in clinical practice. In addition, these findings lay the groundwork for future research and the development of standardized protocols, ultimately improving the management of vulnerable populations in the ongoing fight against COVID-19.

ABSTRACTObjectivesTransnasal endoscopic sphenopalatine artery ligation (TESPAL) has been proposed as a first‐line therapy for intractable epistaxis before utilizing posterior nasal packing and embolization. A specific procedure code for TESPAL was newly introduced in 2018, adding to two prior codes for procedural control of epistaxis. This study compares all‐time utilization of the TESPAL CPT code in Medicare beneficiaries with alternative procedural codes for epistaxis management.MethodsThe publicly available data from the Centers for Medicare and Medicaid Services in the 2013–2022 period was analyzed for the reporting of TESPAL (31241), transcatheter permanent occlusion or embolization of noncentral nervous system, head, or neck (61626), and endoscopic control of epistaxis (31238) codes. Welch two sample t‐test and linear regression were used to characterize CPT code utilization.ResultsFrom 2018 to 2022, TESPAL CPT code reporting averaged 378 instances annually, with a stable utilization trend (p = 0.432). CPT codes 61626 and 31238 averaged 1429 and 3779 instances annually, respectively. CPT 31238 showed a significant decline (p < 0.001), and CPT 61626 showed a stable trend (p = 0.082). There was a significant decline in CPT code 31238 use after 2018 (p < 0.01). CPT 61626 showed a significant increase in usage post‐2018 (t = 2.90, p = 0.044).ConclusionAfter an initial increase in 2019, TESPAL reporting flattened, while CPT 61626 (which includes all embolization in head and neck vessels) significantly increased post‐2018. As recent studies show significant advantages of TESPAL over embolization, these findings warrant further attention and study.Level of Evidence3.

Abstract Introduction Despite the widespread use of telemedicine to assess patients with intestinal failure (IF) receiving home parenteral nutrition (HPN), satisfaction with remote consultation methods has not been comprehensively assessed. Here, we assessed patient and clinician attitudes to telephone and video IF consultations. Methods Telemedicine questionnaires were designed and distributed in paper form to patients with IF receiving HPN under the care of a UK national IF reference center and electronically to IF clinicians in Europe, North America, Australia, and New Zealand. Results Seventy‐eight patients (53 women and 25 men) and 110 clinicians agreed to complete the questionnaires. Sixty seven percent of patients who had telephone consultations and 50% of patients who had video consultations were satisfied with their consultations. Forty nine percent and 83% of patients who had telephone and video consultations, respectively, felt they were of the same standard as their face‐to‐face consultations. Despite 60% of clinicians feeling telemedicine training would be useful, 55% of clinicians stated they mostly or always met all of the needs of their patients via telephone consultations, whereas 96% of clinicians felt similarly for video consultations ( P = 0.002). A total of 33% and 57% of clinicians felt telephone and video consultations, respectively, were of the same standard as face‐to‐face consultations ( P = 0.004). Conclusion This study comprehensively assesses attitudes to IF telemedicine consultations. Our data show that a large proportion of patients and clinicians are satisfied with IF telephone and video consultations. However, there is an unmet need amongst clinicians for telemedicine training.