Faculty Bibliography

BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta (REBOA) could prevent lethal exsanguination and support cardiopulmonary resuscitation. In prehospital trauma and medical emergency settings, a small population with high mortality rates could potentially benefit from early REBOA deployment. However, its use in these situations remains highly disputed. Since publication of the first Delphi study on REBOA, in which consensus was not reached on all addressed topics, new literature has emerged. The aim of this study was to establish consensus on the use and implementation of REBOA in civilian prehospital settings for noncompressible truncal hemorrhage and out-of-hospital cardiac arrest as well as for various in-hospital settings. METHODS:A Delphi study consisting of three rounds of questionnaires was conducted based on a review of recent literature. REBOA experts with different medical specialties, backgrounds, and work environments were invited for the international panel. Consensus was reached when a minimum of 75% of panelists responded to a question and at least 75% (positive) or less than 25% (negative) of these respondents agreed on the questioned subject. RESULTS:Panel members reached consensus on potential (contra)indications, physiological thresholds for patient selection, the use of ultrasound and practical, and technical aspects for early femoral artery access and prehospital REBOA. CONCLUSION/CONCLUSIONS:The international expert panel agreed that REBOA can be used in civilian prehospital settings for temporary control of noncompressible truncal hemorrhage, provided that personnel are properly trained and protocols are established. For prehospital REBOA and early femoral artery access, consensus was reached on (contra)indications, physiological thresholds and practical aspects. The panel recommends the initiation of a randomized clinical trial investigating the use of prehospital REBOA for noncompressible truncal hemorrhage. LEVEL OF EVIDENCE/METHODS:Therapeutic/Care Management; Level V.

Dendritic cells (DCs) play a pivotal role in bridging the innate and adaptive immune systems. From their immature state, scavenging tissue for foreign antigens to uptake, then maturation, to their trafficking to lymph nodes for antigen presentation, these cells are exposed to various forms of mechanical forces. Particularly, in the tumor microenvironment, it is widely known that microenvironmental biomechanical cues are heightened. The source of these forces arises from cell-to-extracellular matrix (ECM) and cell-to-cell interactions, as well as being exposed to increased microenvironmental pressures and fluid shear forces typical of tumors. DCs then integrate these forces, influencing their immune functions through mechanotransduction. This aspect of DC biology holds alternative, but important clues to understanding suppressed/altered DC responses in tumors, or allow the artificial enhancement of DCs for therapeutic purposes. This review discusses the current understanding of DC mechanobiology from the perspectives of DCs as sensors of mechanical forces and providers of mechanical forces.

OBJECTIVE:This study aimed to clarify the relationship between oral frailty and oral dysbiosis among hospitalized patients aged ≥ 50 years. METHODS:A prospective observational study was conducted. Number of teeth, masticatory ability, articulatory oral motor skill, tongue pressure, swallowing pressure, and choking were used to assess oral frailty. Saliva samples were collected from the oral cavity for bacterial culture. RESULTS:A total 103 in patients enrolled and 53.4% suffered from oral frailty. Oral frailty was found to have a 3.07-fold correlation with the presence of Enterobacterales in the oral cavity (p = 0.037), especially in poor articulatory oral motor skill, which showed at greater risk of Enterobacterales isolated from the oral cavity by 5.58-fold (p = 0.01). CONCLUSION/CONCLUSIONS:Half of hospitalized patients was found to have oral frailty that was related to more Enterobacterales in the oral cavity. This evidence suggests that the enhancement of articulatory oral motor skills may serve as a potential strategy for mitigating the presence of Enterobacterales within the oral cavity.

Fenestration of the septum between the true and false lumen might be necessary after aortic dissection. We report the technical aspects of in situ laser fenestration of the aortic dissection septum. Two illustrative cases are provided: a 56-year-old man with false lumen deployment of a frozen elephant trunk graft, and a 67-year-old man who underwent fenestrated endovascular aortic repair with a target branch vessel off the false lumen. In both cases, the septum was crossed using in situ laser fenestration. This technique is a precise option to enable passage between true and false lumens during endovascular repair of an aortic dissection.

OBJECTIVE:This study aimed to demonstrate the incidence of altered level of consciousness after hemorrhagic stroke and identify factors associated with altered level of consciousness at 3 mos after stroke. DESIGN:This study used data from a prospective multicenter cohort study conducted in nine hospitals in Korea and included 1677 patients with first-ever hemorrhagic stroke. Patients were dichotomized into those with and without altered level of consciousness at 3 mos after stroke. Multivariate logistic regression analysis was performed to identify factors associated with subacute to chronic stage altered level of consciousness. RESULTS:Among patients with hemorrhagic stroke (age: 20-99 yrs, female 50.21%), the prevalence of altered level of consciousness at admission was 38.58% (25.4% [drowsy], 6.38% [stupor], and 6.8% [coma]) and 17.29% 3 mos after stroke. Multivariate logistic regression analysis revealed that independent factors associated with altered level of consciousness at 3 mos after stroke included late seizure (odds ratio [95% confidence interval], 5.93 [1.78-20.00]), stroke progression (3.84 [1.48-9.64]), craniectomy (2.19 [1.19-4.00]), history of complications (1.74 [1.18-2.55]), age at stroke onset (1.08 [1.07-1.10]), and initial Glasgow Coma Scale score category (0.36 [0.30-0.44]). CONCLUSIONS:The factors associated with altered level of consciousness at 3 mos after stroke should be considered when explaining long-term consciousness status and focused management of modifiable factors in acute care hospitals could help ameliorate altered level of consciousness and promote recovery after stroke.

PURPOSE/OBJECTIVE:Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting. METHODS:The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P. RESULTS:alterations. CONCLUSION/CONCLUSIONS:The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

AIMS/OBJECTIVE:This study aimed to develop an editable structural scaffold for improving drug development, including pharmacokinetics and pharmacodynamics of antibiotics by using synthetic compounds derived from a (hetero)aryl-quinoline hybrid scaffold. METHODS AND RESULTS/RESULTS:In this study, 18 CF3-substituted (hetero)aryl-quinoline hybrid molecules were examined for their potential antibacterial activity against Staphylococcus aureus by determining minimal inhibitory concentrations. These 18 synthetic compounds represent modifications to key regions of the quinoline N-oxide scaffold, enabling us to conduct a structure-activity relationship analysis for antibacterial potency. Among the compounds, 3 m exhibited potency against with both methicillin resistant S. aureus strains, as well as other Gram-positive bacteria, including Enterococcus faecalis and Bacillus subtilis. We demonstrated that 3 m disrupted the bacterial proton motive force (PMF) through monitoring the PMF and conducting the molecular dynamics simulations. Furthermore, we show that this mechanism of action, disrupting PMF, is challenging for S. aureus to overcome. We also validated this PMF inhibition mechanism of 3 m in an Acinetobacter baumannii strain with weaken lipopolysaccharides. Additionally, in Gram-negative bacteria, we demonstrated that 3 m exhibited a synergistic effect with colistin that disrupts the outer membrane of Gram-negative bacteria. CONCLUSIONS:Our approach to developing editable synthetic novel antibacterials underscores the utility of CF3-substituted (hetero)aryl-quinoline scaffold for designing compounds targeting the bacterial proton motive force, and for further drug development, including pharmacokinetics and pharmacodynamics.

OBJECTIVE:Fenestrated-branched endovascular aortic repair (FB-EVAR) has shown favorable outcomes for repair of complex aneurysms and thoracoabdominal aortic aneurysms. Physician-modified endografting (PMEG) and the Gore thoracoabdominal multibranch endoprosthesis (TAMBE) provide custom and off-the-shelf devices for FB-EVAR, respectively. This study compares the outcomes of TAMBE and PMEG at a single institution. METHODS:A retrospective review of patients who underwent TAMBE as part of the multicenter pivotal trial or PMEG as part of a prospective physician-sponsored investigational device exemption at a single institution between 2020 and 2022 were completed. Patient demographics, characteristics, and perioperative and midterm outcomes were compared. RESULTS:A total of 68 patients were included, with 12 in the TAMBE group and 56 in the PMEG group. Baseline characteristics were comparable between groups. Aneurysm type was most often thoracoabdominal aortic aneurysm in both groups (58% TAMBE and 52% PMEG). TAMBE had a higher rate of upper extremity access (100% vs 63%; P = .013) and longer mean procedure time (247 ± 36 minutes vs 189 ± 49 minutes; P < .001). Other intraoperative metrics were similar between groups. Technical success was 100% in TAMBE and 95% in PMEG (P = .412). There was no 30-day mortality in either group. No major adverse events occurred with TAMBE, whereas in PMEG cases, 2% had respiratory failure, 2% required dialysis, and 4% experienced spinal cord ischemia. Although the overall endoleak rates were similar (50% of TAMBE vs 41% of PMEG; P = .57), type II endoleaks accounted for all of the endoleaks in the TAMBE group, whereas type I or III endoleaks were seen in 11% of PMEG patients. At a median follow-up of 26.7 months for the TAMBE group and 21.2 months for the PMEG group, target vessel instability was seen in 10.4% of TAMBE, and 6.9% of PMEG targeted branches (P = .401). Reintervention was required in 33% of TAMBE patients and 27% of PMEG patients (P = .646). Estimated freedom from reintervention rates at 3 years were similar (56% TAMBE vs 62% PMEG, log-rank P = .910). Freedom from visceral renal target vessel instability at 3 years was 89% for both groups (log-rank P = .459). The Kaplan-Meier 3-year estimated survival was 100% for patients in the TAMBE group and 77% for patients in the PMEG group (log-rank P = .157). CONCLUSIONS:At experienced centers, FB-EVAR can be completed with PMEG or TAMBE with comparable, excellent perioperative and midterm outcomes. Reinterventions are frequently needed for both TAMBE and PMEG.