Risk factors associated with the severity of pericoronitis of mandibular third molar.

PURPOSE: The factors related to pericoronitis severity are unclear, and this study aimed to address this knowledge gap. MATERIALS AND METHODS: In total, 113 patients with pericoronitis were included, and their demographic, clinical, and radiographic characteristics were recorded. The Patient-Clinician Pericoronitis Classification was used to score and categorize the severity of pericoronitis. Statistical analysis was conducted to examine the participants' characteristics, validity of the Patient-Clinician Pericoronitis Classification, and risk factors associated with the severity of pericoronitis. RESULTS: The demographic, clinical, and radiographic characteristics of males and females were similar, except for Winter's classification, pain, and intraoral swelling. The constructive validity of the Patient-Clinician Pericoronitis Classification was confirmed with three latent factors, including infection level, patient discomfort, and social interference. Ordinal logistic multivariate regression analysis revealed that upper respiratory tract infection was the sole risk factor associated with pericoronitis severity in males (odds ratio = 4.838). In females, pericoronitis on the right side (odds ratio = 2.486), distal radiolucency (odds ratio = 5.203), and menstruation (odds ratio = 3.416) were significant risk factors. CONCLUSION: This study demonstrated the constructive validity of the Patient-Clinician Pericoronitis Classification. Among females, pericoronitis in mandibular third molars on the right side with radiolucency in menstruating individuals was more severe. In males, upper respiratory tract infection was the sole risk factor associated with pericoronitis severity. CLINICAL RELEVANCE: Individuals with risk factors should be aware of severe pericoronitis in the coming future.

A sulfonate ligand-defected Zr-based metal-organic framework for the enhanced selective removal of anionic dyes.

In this work, we introduce a novel defective analogue of the representative 6-connected zirconium-based metal-organic framework (MOF-808), by employing 5-sulfoisophthalic acid monosodium salt (H2BTC-SO3Na) as a defect inducer via a mixed-linker approach. The structural integrity and different physicochemical properties were investigated by various characterization techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen physisorption at 77 K. Additionally, proton nuclear magnetic resonance (1H-NMR), energy-dispersive X-ray (EDX), and inductively coupled plasma optical emission spectroscopy (ICP-OES) were employed to confirm the presence of 6.9 mol% of the 5-sulfoisophthalate ligand within the highly crystalline MOF-808 structure. The defective material exhibited significant enhancements in the removal efficiency of various organic dyes, including approximately 64% and 77% for quinoline yellow and sunset yellow, and 56% and 13% for rhodamine B and malachite green, compared to its pristine counterpart. Importantly, the defective MOF-808 showed a remarkable selectivity toward anionic species in binary-component dyes comprising both anionic and cationic dyes.

Prior abdominal surgery is not associated with 30-day mortality or morbidities after endovascular repair of complex abdominal aortic aneurysm.

BACKGROUND: Prior abdominal surgery (PAS) has the potential to affect outcomes of abdominal aortic aneurysm (AAA) repair. Recently, endovascular aneurysm repair (EVAR) has been expanded among patients with complex AAA, which involves visceral branches in the upper abdominal aortic. However, outcomes of EVAR for complex AAA in patients with PAS have not been examined. This study aimed to investigate the impact of PAS on 30-day outcomes in EVAR for complex AAA. METHODS: Patients who underwent EVAR for complex AAA were identified in ACS-NSQIP targeted database from 2012 to 2022. Complex AAA was defined as juxtarenal, suprarenal, or pararenal proximal extent, Type IV thoracoabdominal aneurysm, or aneurysms treated with Zenith Fenestrated endograft. Patients with age less than 18 years, ruptured AAA with or without hypotension, acute intraoperative conversion to open, and emergency presentation were excluded. Multivariable logistic regression was used to compare 30-day postoperative outcomes of patients with and without PAS. Demographics, baseline characteristics, aneurysm diameter, indication for surgery, proximal and distant aneurysm extent, anesthesia, and concomitant procedures were adjusted. RESULTS: There were 515 (28.34%) and 1302 (71.66%) patients with and without PAS, respectively, who underwent EVAR for complex AAA. Patients with and without PAS had comparable 30-day mortality (3.11% vs 3.00%, aOR = 0.766, 95 CI = 0.407-1.442, p = .41). Organ system complications including cardiac complications, stroke, pulmonary complications, and renal complications were comparable between patients with and without PAS. All other 30-day outcomes were similar between groups. However, patients with PAS had higher 30-day readmission rate (11.65% vs 7.14%, aOR = 1.634, 95 CI = 1.145-2.331, p = .01). CONCLUSION: While PAS has high prevalence among patients undergoing EVAR for complex AAA, it does not impact 30-day mortality and morbidities. Thus, EVAR for complex AAA can be considered safe for patients with PAS in terms of short-term outcomes, despite the long-term prognosis in these patients being needed in further studies.

Adverse Events from Fluoroscopic versus Portable Placement of PICCs and CVCs in Pediatric Patients.

PURPOSE: To evaluate the outcomes of fluoroscopic versus portable placement of peripherally inserted central catheters (PICCs) and central venous catheters (CVCs) in pediatric patients. MATERIALS AND METHODS: This is a single-center, retrospective review of 346 upper-extremity PICCs (286 fluoroscopic, 60 portable), mean age = 9.83 ± 5.58 years, 49.1% female; and 138 tunneled femoral CVCs (56 fluoroscopic, 82 portable), mean age = .23 ± .36 years, 57.0% female. Portable placements used mobile plain-film radiography. All lines were placed by board-certified interventional radiologists. RESULTS: Fluoroscopic PICC versus portable PICC placements had a lower procedure time (43.9 vs. 57.9 minutes, P<.001); radiation dosage (342 vs. 590 mGy.cm2, P<.001); incidence of technical failure (0 vs. 3.3%, P=.029); incidence of catheter malfunction (1.7% vs. 12.1%, P<.001). Fluoroscopic CVC versus portable CVC placements had a lower procedure time (42.6 vs 54.8 minutes, P<.001); and radiation dosage (63.8 vs 405 mGy.cm2, P<.001). No technical failures were found in either CVC groups and the difference was non-significant for catheter malfunction (0 vs 7.3%, P=.081). Fluoroscopic placements of PICCs and CVCs had a lower incidence rate of central line-associated bloodstream infection (CLABSI) compared to portable placements (.71 vs 2.22 cases per 1000 line-day, P=.046). Overall, fluoroscopic placements of PICCs and CVCs had fewer adverse events compared to portable placements (3.2% vs 14.8%, P<.001). Portable procedure was the only significant factor associated with adverse events (OR, 33.77 (4.56-757.01)). CONCLUSIONS: Fluoroscopic placements of PICCs and CVCs are associated with lower procedure time, radiation dose, and risk of adverse events compared to portable placements in pediatric patients.

Contemporary trends of leadless pacemaker implantation in the United States.

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.

Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment.

Background: Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation. Methods: Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment. Results: Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco. Conclusion: This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.

Pericardial effusion requiring intervention in patients undergoing leadless pacemaker implantation: A real-world analysis from the National Inpatient Sample database.

Background: Pericardial effusion requiring percutaneous or surgical-based intervention remains an important complication of a leadless pacemaker implantation. Objective: The study sought to determine real-world prevalence, risk factors, and associated outcomes of pericardial effusion requiring intervention in leadless pacemaker implantations. Methods: The National Inpatient Sample and International Classification of Diseases-Tenth Revision codes were used to identify patients who underwent leadless pacemaker implantations during the years 2016 to 2020. The outcomes assessed in our study included prevalence of pericardial effusion requiring intervention, other procedural complications, and in-hospital outcomes. Predictors of pericardial effusion were also analyzed. Results: Pericardial effusion requiring intervention occurred in a total of 325 (1.1%) leadless pacemaker implantations. Patient-level characteristics that predicted development of a serious pericardial effusion included >75 years of age (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75), female sex (OR 2.03, 95% CI 1.62-2.55), coagulopathy (OR 1.50, 95% CI 1.12-1.99), chronic pulmonary disease (OR 1.36, 95% CI 1.07-1.74), chronic kidney disease (OR 1.53, 95% CI 1.22-1.94), and connective tissue disorders (OR 2.98, 95% CI 2.02-4.39). Pericardial effusion requiring intervention was independently associated with mortality (OR 5.66, 95% CI 4.24-7.56), prolonged length of stay (OR 1.36, 95% CI 1.07-1.73), and increased cost of hospitalization (OR 2.49, 95% CI 1.92-3.21) after leadless pacemaker implantation. Conclusion: In a large, contemporary, real-world cohort of leadless pacemaker implantations in the United States, the prevalence of pericardial effusion requiring intervention was 1.1%. Certain important patient-level characteristics predicted development of a significant pericardial effusion, and such effusions were associated with adverse outcomes after leadless pacemaker implantations.

Activation of fluoride anion as nucleophile in water with data-guided surfactant selection.

A principal component surfactant_map was developed for 91 commonly accessible surfactants for use in surfactant-enabled organic reactions in water, an important approach for sustainable chemical processes. This map was built using 22 experimental and theoretical descriptors relevant to the physicochemical nature of these surfactant-enabled reactions, and advanced principal component analysis algorithms. It is comprised of all classes of surfactants, i.e. cationic, anionic, zwitterionic and neutral surfactants, including designer surfactants. The value of this surfactant_map was demonstrated in activating simple inorganic fluoride salts as effective nucleophiles in water, with the right surfactant. This led to the rapid development (screening 13-15 surfactants) of two fluorination reactions for ß-bromosulfides and sulfonyl chlorides in water. The latter was demonstrated in generating a sulfonyl fluoride with sufficient purity for direct use in labelling of chymotrypsin, under physiological conditions.

Locoregional Anesthesia Has Lower Risks of Cardiac Complications Than General Anesthesia After Prolonged Endovascular Repair of Abdominal Aortic Aneurysms.

OBJECTIVES: Although general anesthesia is the primary anesthesia in endovascular aneurysm repair (EVAR), some studies suggest locoregional anesthesia could be a feasible alternative for eligible patients. However, most evidence was from retrospective studies and was subjected to an inherent selection bias that general anesthesia is often chosen for more complex and prolonged cases. To mitigate this selection bias, this study aimed to compare 30-day outcomes of prolonged, nonemergent, intact, infrarenal EVAR in patients undergoing locoregional or general anesthesia. In addition, risk factors associated with prolonged operative time in EVAR were identified. DESIGN: Retrospective large-scale national registry study. SETTING: American College of Surgeons National Surgical Quality Improvement Program targeted database from 2012 to 2022. PARTICIPANTS: A total of 4,075 out of 16,438 patients (24.79%) had prolonged EVAR. Among patients with prolonged EVAR, 324 patients (7.95%) were under locoregional anesthesia. There were 3,751 patients (92.05%) under general anesthesia, and 955 of them were matched to the locoregional anesthesia cohort. INTERVENTIONS: Patients undergoing infrarenal EVAR were included. Exclusion criteria included age <18 years, emergency cases, ruptured abdominal aortic aneurysm, and acute intraoperative conversion to open. Only cases with prolonged operative times (>157 minutes) were selected. A 1:3 propensity-score matching was used to address demographics, baseline characteristics, aneurysm diameter, distant aneurysm extent, and concomitant procedures between patients under locoregional and general anesthesia. Thirty-day postoperative outcomes were assessed. Moreover, factors associated with prolonged EVAR were identified by multivariate logistic regression. MEASUREMENTS AND MAIN RESULTS: Except for general anesthesia contraindications, patients undergoing locoregional or general anesthesia exhibited largely similar preoperative characteristics. After propensity-score matching, patients under locoregional and general anesthesia had a lower risk of myocardial infarction (0.93% v 2.83%, p = 0.04), but comparable 30-day mortality (3.72% v 2.72%, p = 0.35) and other complications. Specific concomitant procedures, aneurysm anatomy, and comorbidities associated with prolonged EVAR were identified. CONCLUSIONS: Locoregional anesthesia can be a safe and effective alternative to general anesthesia, particularly in EVAR cases with anticipated complexity and prolonged operative times, as it offers the potential benefit of reduced cardiac complications. Risk factors associated with prolonged EVAR can aid in preoperative risk stratification and inform the decision-making process regarding anesthesia choice.

A domain-swapped CaMKII conformation facilitates linker-mediated allosteric regulation.

Ca2+ signaling plays a key role in physiological processes such as memory formation and cardiac function. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is the primary kinase that responds to Ca2+ inputs in these cells. There are four CaMKII paralogs in mammals which are alternatively spliced in the variable linker region to create upwards of 70 different variants. In this study, we systematically studied different linker regions and determined that the position of charged residues within the linker region modulates the Ca2+/CaM sensitivity of the holoenzyme. We present an X-ray crystal structure of full-length CaMKIIδ that shows a domain-swapped conformation of the subunits within the dodecameric holoenzyme. In this structure, the kinase domain of one subunit is docked onto the hub domain of a different subunit, providing an additional interface within the holoenzyme. Mutations at the equatorial and lateral interfaces revealed that the kinase-hub interaction dissociates as the hub-hub interfaces are disturbed, which led alterations in the stoichiometry of CaMKII holoenzyme and Ca2+/CaM sensitivity. Molecular dynamics simulations of linker-containing domain-swapped and non-domain-swapped CaMKIIs reveal that the domain-swapped configuration facilitates an interaction between the calmodulin binding domain and the variable linker region, such that dynamic electrostatic forces between charges on these segments can modulate the equilibrium between the compact and extended conformational states of the holoenzyme. Small angle X-ray scattering data confirms that a negatively charged linker CaMKII holoenzyme adopts a more compact conformation compared to a positively charged linker. These data support a model where patches of charged linker residues interact with the calmodulin binding domain to allosterically regulate sensitivity to Ca2+/CaM. Our findings provide a new framework for understanding CaMKII structure and allosteric regulation by the variable linker region in Ca2+-sensitive cells.

Adaptive response of Pseudomonas aeruginosa under serial ciprofloxacin exposure.

Understanding the evolution of antibiotic resistance is important for combating drug-resistant bacteria. In this work, we investigated the adaptive response of Pseudomonas aeruginosa to ciprofloxacin. Ciprofloxacin-susceptible P. aeruginosa ATCC 9027, CIP-E1 (P. aeruginosa ATCC 9027 exposed to ciprofloxacin for 14 days) and CIP-E2 (CIP-E1 cultured in antibiotic-free broth for 10 days) were compared. Phenotypic responses including cell morphology, antibiotic susceptibility, and production of pyoverdine, pyocyanin and rhamnolipid were assessed. Proteomic responses were evaluated using comparative iTRAQ labelling LC-MS/MS to identify differentially expressed proteins (DEPs). Expression of associated genes coding for notable DEPs and their related regulatory genes were checked using quantitative reverse transcriptase PCR. CIP-E1 displayed a heterogeneous morphology, featuring both filamentous cells and cells with reduced length and width. By contrast, although filaments were not present, CIP-E2 still exhibited size reduction. Considering the MIC values, ciprofloxacin-exposed strains developed resistance to fluoroquinolone antibiotics but maintained susceptibility to other antibiotic classes, except for carbapenems. Pyoverdine and pyocyanin production showed insignificant decreases, whereas there was a significant decrease in rhamnolipid production. A total of 1039 proteins were identified, of which approximately 25 % were DEPs. In general, there were more downregulated proteins than upregulated proteins. Noted changes included decreased OprD and PilP, and increased MexEF-OprN, MvaT and Vfr, as well as proteins of ribosome machinery and metabolism clusters. Gene expression analysis confirmed the proteomic data and indicated the downregulation of rpoB and rpoS. In summary, the response to CIP involved approximately a quarter of the proteome, primarily associated with ribosome machinery and metabolic processes. Potential targets for bacterial interference encompassed outer membrane proteins and global regulators, such as MvaT.

Omics analysis unveils changes in the metabolome and lipidome of Caenorhabditis elegans upon polydopamine exposure.

Polydopamine (PDA) is an insoluble biopolymer with a dark brown-black color that forms through the autoxidation of dopamine. Because of its outstanding biocompatibility and durability, PDA holds enormous promise for various applications, both in the biomedical and non-medical domains. To ensure human safety, protect health, and minimize environmental impacts, the assessment of PDA toxicity is important. In this study, metabolomics and lipidomics assessed the impact of acute PDA exposure on Caenorhabditis elegans (C. elegans). The findings revealed a pronounced perturbation in the metabolome and lipidome of C. elegans at the L4 stage following 24 hours of exposure to 100 µg/mL PDA. The changes in lipid composition varied based on lipid classes. Increased lipid classes included lysophosphatidylethanolamine, triacylglycerides, and fatty acids, while decreased species involved in several sub-classes of glycerophospholipids and sphingolipids. Besides, we detected 37 significantly affected metabolites in the positive and 8 in the negative ion modes due to exposure to PDA in C. elegans. The metabolites most impacted by PDA exposure were associated with purine metabolism, biosynthesis of valine, leucine, and isoleucine; aminoacyl-tRNA biosynthesis; and cysteine and methionine metabolism, along with pantothenate and CoA biosynthesis; the citrate cycle (TCA cycle); and beta-alanine metabolism. In conclusion, PDA exposure may intricately influence the metabolome and lipidome of C. elegans. The combined application of metabolomics and lipidomics offers additional insights into the metabolic perturbations involved in PDA-induced biological effects and presents potential biomarkers for the assessment of PDA safety.

Association of chronic kidney disease and end-stage renal disease with procedural complications and inpatient outcomes of leadless pacemaker implantations across the United States.

BACKGROUND: Leadless pacemakers have emerged as a promising alternative to transvenous pacemakers in patients with kidney disease. However, studies investigating leadless pacemaker outcomes and complications based on kidney dysfunction are limited. OBJECTIVE: The objective of this study was to evaluate the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with inpatient complications and outcomes of leadless pacemaker implantations. METHODS: National Inpatient Sample and International Classification of Diseases, Tenth Revision codes were used to identify patients with CKD and ESRD who underwent leadless pacemaker implantations in the United States from 2016 to 2020. Study end points assessed included inpatient complications, outcomes, and resource utilization of leadless pacemaker implantations. RESULTS: A total of 29,005 leadless pacemaker placements were identified. Patients with CKD (n = 5245 [18.1%]) and ESRD (n = 3790 [13.1%]) were younger than patients without CKD and had higher prevalence of important comorbidities. In crude analysis, ESRD was associated with higher prevalence of major complications, peripheral vascular complications, and inpatient mortality. After multivariable adjustment, CKD and ESRD were associated with inpatient mortality (CKD: adjusted odds ratio [aOR], 1.62 [95% CI, 1.40-1.86]; ESRD: aOR, 1.38 [95% CI, 1.18-1.63]) and prolonged length of stay (CKD: aOR, 1.55 [95% CI, 1.46-1.66]; ESRD: aOR, 1.81 [95% CI 1.67-1.96]). ESRD was also associated with higher hospitalization costs (aOR, 1.63; 95% CI, 1.50-1.77) and major complications (aOR, 1.33; 95% CI, 1.13-1.57) after leadless pacemaker implantation. CONCLUSION: Approximately one-third of patients undergoing leadless pacemaker implantation had CKD or ESRD. CKD and ESRD were associated with greater length and cost of stay and inpatient mortality.

The Association between Red Blood Cell Distribution Width and Mortality Risk after Hip Fracture: A Meta-Analysis.

Background and Objectives: Hip fractures in the elderly pose a considerable health risk and cause concern. Red blood cell distribution width (RDW) is a valuable marker for identifying patients at high risk of age-related mortality and various disorders and diseases. However, its association with poor patient outcomes following hip fractures has yet to be fully established. Hence, the purpose of this meta-analysis was to investigate and gain a better understanding of the relationship between RDW levels and the risk of mortality after hip fractures. Materials and Methods: PubMed, Embase, Web of Science, and other databases were comprehensively searched until April 2023 to identify relevant studies. The meta-analysis included observational studies finding the association between RDW at admission or preoperation and short-term and long-term mortality rates following hip fractures. The results were presented in terms of odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results: This meta-analysis included 10 studies involving 5834 patients with hip fractures. Patients with preoperative RDW of over 14.5% had higher risks of 1-year (OR: 5.40, 95% CI: 1.89-15.48, p = 0.002) and 3-month (OR: 2.91, 95% CI: 1.42-5.95, p = 0.004) mortality. Higher admission or preoperative RDW was significantly associated with an 11% higher mortality risk after 1 year (HR: 1.11, 95% CI: 1.06-1.17, p < 0.00001). Patients with higher preoperative RDW had a significantly higher risk of 6-month mortality, which was three times that of those with lower preoperative RDW (OR: 3.00, 95% CI: 1.60-5.61, p = 0.0006). Higher preoperative RDW was correlated to a higher 30-day mortality risk (OR: 6.44, 95% CI: 3.32-12.47, p < 0.00001). Conclusions: Greater RDW values at admission or before surgery were associated with a higher risk of short-term and long-term mortality following hip fractures. Because RDW can be easily measured using a routine blood test at a low cost, this parameter is promising as an indicator of mortality in elderly patients with hip fractures.

Antiangiogenic Therapeutic mRNA Delivery Using Lung-Selective Polymeric Nanomedicine for Lung Cancer Treatment.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

The 5-Factor Modified Frailty Index is a Succinct yet Effective Predictor of Adverse Outcomes in Patients Undergoing Open Surgery for Abdominal Aortic Aneurysm.

BACKGROUND: Frailty is an age-related, clinically recognizable state marked by increased susceptibility. The 5-item Modified Frailty Index (mFI-5) offers a concise assessment of frailty and has demonstrated its efficacy in various surgical fields. While the mFI-5 has been validated for endovascular aneurysm repair for abdominal aortic aneurysm (AAA), its applicability in open surgical repair (OSR) for AAA remains largely unexplored. This study sought to evaluate the utility of mFI-5 in predicting 30-day outcomes following OSR for AAA. METHODS: Patients underwent OSR for AAA were identified in American College of Surgeons National Surgical Quality Improvement Program-targeted database from 2012 to 2021. Patients were stratified into 3 cohorts: mFI-5 score of 0 (control), 1, and 2+. Multivariable logistic regression was used to compare 30-day perioperative outcomes between frail patients and controls adjusting preoperative variables with P value <0.1. RESULTS: Of the 5,249 patients who underwent OSR for AAA, 1,043 were controls, 2,938 had an mFI-5 score of 1 and 1,268 had an mFI-5 score of 2+. When compared to the control group, patients with an mFI-5 = 1 were more likely to have pulmonary events (adjusted odds ratio (aOR) = 1.452, P < 0.01), bleeding events (aOR = 1.33, P < 0.01), wound complications (aOR = 2.214, P < 0.01), ischemic colitis (aOR = 1.616, P = 0.01), and unplanned reoperation (aOR = 1.292, P = 0.04). Those with an mFI-5 = 2+ demonstrated higher risks of mortality (aOR = 1.709, P < 0.01), major adverse cardiovascular events (aOR = 1.347, P = 0.04), pulmonary events (aOR = 2.045, P < 0.01), renal dysfunction (aOR = 1.568, P < 0.01), sepsis (aOR = 1.587, P = 0.01), bleeding events (aOR = 1.429, P < 0.01), wound complications (aOR = 2.338, P < 0.01), ischemic colitis (aOR = 1.775, P = 0.01), unplanned reoperation (aOR = 1.445, P = 0.01), operation over 4 hours (aOR = 1.34, P < 0.01), length of stay over 7 days (aOR = 1.324, <0.01), discharge not to home (aOR = 1.547, P < 0.01), 30-day readmission (aOR = 1.657, P = 0.01). CONCLUSIONS: The mFI-5 emerges as a succinct yet effective indicator of frailty for patients undergoing OSR for AAA. Especially, an mFI-5 score of 2+ is linked with increased 30-day mortality and complications. As such, mFI-5 can be used as a valuable screening tool for frailty in patients undergoing OSR for AAA.

Letter re: Misidentification of Transcarotid Artery Revascularization by Current Procedural Terminology.

In this letter, we discussed the selection of patients undergoing Transcarotid Artery Revascularization (TCAR) using the Current Procedural Terminology (CPT) codes. We examined a previous study using CPT code 37215 to identify TCAR cases using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. As an ACS-NSQIP participating site, we have complete access to the ACS-NSQIP database, and we performed a more in-depth examination of the method. We found significant discrepancies in the method described and conclude that it is methodologically flawed to use CPT code 37215 to differentiate TCAR cases. This study not only re-evaluates the validity of the previous study but also has the potential to prevent other researchers from employing the erroneous methodology for TCAR selection using the CPT code, which is one of the most widely used standardizations of medical communication for surgical procedures. This is particularly pertinent given the recent "TCAR revolution", where significant attention has been focused on TCAR.

Access to primary eye care for people living with dementia: a call to action for primary care practitioners to 'think vision'.

Access to allied health services offers significant benefits for people living with dementia, yet access is currently fragmented and inconsistent. The 2023-2024 budget allocated AU$445million to further enable general practice-led, multidisciplinary teams, with integrated care located within practices, including employment of allied health professionals. Such team care models are recognised by The Royal Australian College of General Practitioners as vital to delivery of high-quality care for older adults. They are especially relevant for over 250,000 Australians who live with dementia in the community. However, not all allied health professionals are currently based within general practices. Future, sustainable general practice-led models of multidisciplinary care that connect patients with external allied health providers could be considered for a comprehensive and collaborative approach to care. Our focus is on people living with dementia, who are at greater risk of preventable vision impairment. Poor vision and/or ocular health can be detected and managed through regular eye examinations, which are predominantly delivered by community-based optometrists in Australia, in a primary care capacity. However, people living with dementia are also less likely to have regular eye examinations. In this paper, we highlight the value of ensuring access to primary eye care services as part of post-diagnosis dementia care. We illustrate the important role of primary care practitioners in building and sustaining connections with allied health professions, like optometry, through effective referral and interprofessional communication systems. This can help break down access barriers to dementia-friendly eye care, through promoting the importance of regular eye tests for people living with dementia.

Conamonin A and dihydrochalcones from the whole plants of Conamomum rubidum (Lamxay & N.S.Lý) Skornick. & A.D. Poulsen showing anti-inflammatory and cytotoxic activities.

A new compound, conamonin A (1), was isolated from the whole plants of Conamomum rubidum with eight known dihydrochalcones (2-9). Their structures were elucidated by a combination of spectroscopic methods as well as by comparison with previously reported data. The absolute configuration of 1 was assigned by TDDFT-ECD method. Compounds 1 and 8 showed inhibitory activity against LPS-induced NO production in the RAW 264.7 cells, with IC50 values of 58.29 ± 2.88 and 81.77 ± 5.99 µM, respectively. Compounds 3/4 and 5/6 exhibited inhibitory effects, with IC50 values of 28.76 ± 1.16 and 29.89 ± 1.79 µg/mL, respectively. Compounds 2, 7-9 exhibited significant cytotoxic activity against human lung carcinoma (the SK-LU-1 cell line) with IC50 values ranging from 9.87 to 17.99 µM. This study offers valuable insights into the chemical constituents and biological activities of Conamomum rubidum, highlighting its potential as a source for discovering new anti-inflammatory and cytotoxic agents.

Acute Intraoperative Conversion from Endovascular to Open vs Planned Open Operation for Abdominal Aortic Aneurysm: A Propensity-Score Matched Study from the American College of Surgeons NSQIP Targeted Database.

BACKGROUND: Evaluating outcomes for acute intraoperative conversion to open surgery during endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) was difficult due to low incidence. This study aimed to compare 30-day outcomes between patients with acute intraoperative conversion during EVAR and planned open surgery, and to identify risk factors associated with acute conversion. METHODS: Patients underwent EVAR or planned open AAA repair were identified in ACS-NSQIP targeted databases 2012-2021. Patients with acute intraoperative conversion during EVAR were selected. A 1:3 propensity-score matching was used to match demographics, baseline characteristics, surgical indications, aneurysm size and extent, and emergency cases between the conversion open and planned open groups. Thirty-day postoperative outcomes were assessed. RESULTS: Out of 20,566 EVAR, 177 (0.86%) had acute intraoperative conversion to open surgery. The conversion open group was matched to 504 out of 5,249 planned open patients. Conversion open and planned open groups had comparable 30-day mortality (23.43% vs 17.46%, p=0.09) and organ system complications including MACE (14.86% vs 10.71%, p=0.17), pulmonary complications (17.71% vs 24.01%, p=0.09), and renal complications (8.57% vs 11.11%, p=0.39). The conversion open group had lower bleeding requiring transfusion (48.57% vs 75.60%, p<0.01), shorter operation time (p<0.01), and shorter length of stay (p<0.01). Other postoperative outcomes did not differ. Risk factors associated with acute intraoperative conversion included ruptured aneurysm with or without hypotension. Protective factors included hypertension and aortic distal aneurysm extent. CONCLUSION: While this study does not endorse a universal "EVAR first" strategy for all patients with AAA, EVAR can be attempted first in eligible AAA patients. Even when EVAR is unsuccessful, intraoperative conversion to open surgery still appears to be safe compared to planned open repair.