Association Of Estimated Plasma Volume with New Onset Acute Kidney Injury in Hospitalized COVID-19 Patients.

PURPOSE: To explore the association of estimated plasma volume (ePV) and plasma volume status (PVS) as surrogates of volume status with new-onset AKI and in-hospital mortality among hospitalized COVID-19 patients. MATERIALS AND METHODS: We performed a retrospective multi-center study on COVID-19-related ARDS patients who were admitted to the Mayo Clinic Enterprise health system. Plasma volume was calculated using the formulae for ePV and PVS, and longitudinal analysis was performed to find the association of ePV and PVS with new-onset AKI during hospitalization as the primary outcome and in-hospital mortality as a secondary outcome. RESULTS: Our analysis included 7616 COVID-19 patients with new-onset AKI occurring in 1365 (17.9%) and a mortality rate of 25.96% among them. A longitudinal multilevel multivariate analysis showed both ePV (OR 1.162; 95% CI 1.048-1.288, p=0.004) and PVS (OR 1.032; 95% CI 1.012-1.050, p=0.001) were independent predictors of new onset AKI. Higher PVS was independently associated with increased in-hospital mortality (OR 1.038, 95% CI 1.007-1.070, p=0.017), but not ePV (OR 0.868, 95% CI 0.740-1.018, p=0.082). CONCLUSION: A higher PVS correlated with a higher incidence of new-onset AKI and worse outcomes in our cohort of hospitalized COVID-19 patients. Further large-scale and prospective studies are needed to understand its utility.

Knowledge, attitudes, and practices associated with influenza vaccine uptake among healthcare personnel in Israel during three influenza seasons, 2016-2019.

INTRODUCTION: Despite a longstanding Israel Ministry of Health recommendation that all healthcare personnel (HCP) receive a seasonal influenza vaccine, vaccine uptake among HCP remains below the country's target of 60% coverage. To understand factors related to vaccine hesitancy, we used data from a prospective three-year (2016-2019) influenza vaccine effectiveness study among Israeli HCP to examine knowledge, attitudes, and practices (KAP) about influenza vaccination and their association with vaccine uptake. METHODS: At the start of each influenza season, all participating HCP completed a questionnaire that included questions about socio-demographic and occupational characteristics, health status, and KAP related to seasonal influenza vaccination. We extracted vaccination history from electronic medical records and employee vaccination registries. We used logistic regression models to identify demographic and occupational factors, and KAP about influenza vaccination, associated with receipt of vaccination. RESULT: A total of 2,126 HCP were enrolled and had available data on vaccination history. Their median age was 42 years [IQR 35-52], and 73 % self-identified as female. Influenza vaccine uptake in 2016, 2017 and 2018 was 46 %, 48 % and 47 %, respectively. Overall, 36 % of HCP had received an influenza vaccine in ≥ 4 of the eight years prior. HCP aged 35-49 years were less likely to receive influenza vaccine compared to HCP aged ≥ 50 years (OR: 0.81 [95 % CI: 0.67-0.98]). Nurses and allied personnel were less likely to receive influenza vaccine compared to physicians (OR: 0.63 [95 % CI: 0.50-0.78] and OR: 0.53 [95 % CI: 0.40-0.70], respectively). The emotional benefit of vaccination (e.g., anticipating regret if not vaccinated) and the perception of vaccine safety were factors associated with vaccine uptake (OR: 7.60 [95 % CI: 6.27-9.22] and OR: 3.43 [95 % CI:2.91-4.03], respectively). CONCLUSION: Among HCP at two hospitals in Israel, less than half received an annual influenza vaccine. Older HCP, physicians, and those who reported the emotional benefit of vaccination or agreed that influenza vaccines are safe were more likely to be vaccinated. Future influenza vaccination campaigns could focus on these demographic groups and tailor messages emphasizing the emotional benefits of vaccination and vaccine safety to increase seasonal influenza vaccine uptake among HCP in Israel.

Cationic Glucan Dendrimer Gel-Mediated Local Delivery of Anti-OC-STAMP-siRNA for Treatment of Pathogenic Bone Resorption.

Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.

Association of antibiotics with the outcomes in COVID-19 pneumonia patients with elevated PCT levels.

OBJECTIVE: To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels. METHODS: This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients' antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml. RESULTS: Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %). Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders. CONCLUSION: Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction.

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

Impact of the introduction of the national antimicrobial stewardship standard across Queensland Health hospitals: ecological observational study exploring patterns of antimicrobial use.

BACKGROUND: Antimicrobial stewardship programmes are a critical tool for addressing the rising threat of antimicrobial resistance. AIM: To determine changes in patterns of antimicrobial use in Queensland public hospitals following introduction of the National Safety and Quality Health Service antimicrobial stewardship standard. METHODS: A retrospective pre/post intervention study was conducted across Queensland public hospitals at the ecological level using Queensland Health's MedTRx database. An interrupted time-series analysis was performed using linear regression models to determine rates of antimicrobial use by quarterly aggregated defined daily dose per 1000 patient-days, for groups of hospitals stratified by peer group classification. Pre-defined time-periods for antimicrobial stewardship programme implementation in response to the introduction of the standard were analysed. FINDINGS: In the post-intervention period, there was a decrease in overall use of systemic antimicrobials, glycopeptides, carbapenems and fluoroquinolones in principal referral and public acute group A hospitals. A decrease in overall use was also observed for smaller regional and remote public acute group C and D hospitals; however, increases in glycopeptide and fluoroquinolone use were observed. Third-generation cephalosporin use was unchanged for all hospital peer groups. The proportion of overall use that was accounted for by narrow-spectrum penicillin was low for all facilities, with modest improvements in the post-intervention period observed in principal referral facilities only. CONCLUSION: These findings add to current knowledge on the effectiveness of legislative quality standards on antimicrobial stewardship at the macro level and highlight gaps to target for future programmes.

Executive Summary: State-of-the-Art Review: Fostering Collaborative Teamwork-A Comprehensive Approach to Vascular Graft Infection Following Arterial Reconstructive Surgery.

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta.

Fostering Collaborative Teamwork-A Comprehensive Approach to Vascular Graft Infection Following Arterial Reconstructive Surgery.

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta.

Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study.

OBJECTIVE: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. METHODS: The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). RESULTS: Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. CONCLUSIONS: The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Perceptions and Utility of Course Evaluations in US Pharmacy Schools.

OBJECTIVE: This study aimed to describe the purpose, implementation, and perceived utility of course evaluations in pharmacy programs. METHODS: After a literature review, a 34-item survey was developed, pretested, and sent to assessment administrators at accredited pharmacy programs (N = 139) with at least 3 follow-ups. Descriptive and inferential statistics were performed in IBM SPSS Statistics software. RESULTS: A total of 90 programs responded (64.7% response rate). Most students (94%) were offered the opportunity to complete course evaluations. Some students completed evaluations during the course (47%), while others did so within 1 week of completion of the course (49%). Whether or not class time was given for students to complete the survey was often dependent on faculty choice (52.2%). Results were typically released after final grades were posted (92%), in time to use for the next semester of teaching (77%). Faculty were chosen to be evaluated by the number of teaching hours (50%) followed by all instructors (45.6%). Programs used the results for performance reviews by chairs (91%), course coordinator reviews (84%), and committee continuous quality improvement efforts (72%). Most programs did not provide faculty guidance on using evaluations (78%) nor development/mentoring (57%); only 22% of programs offered student development in completing evaluations. CONCLUSION: While most programs invite feedback from all students via evaluations, most did not provide guidance to faculty on how to use this feedback for faculty or course development purposes. A more robust process to optimize the use of course evaluations should be developed.

Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022.

OBJECTIVES: The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, 'What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?' DESIGN/SETTING: We conducted a test-negative case-control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022. PARTICIPANTS: 1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product. RESULTS: We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26-38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56-144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: -7.0% to 63.3%) during the Omicron period. CONCLUSIONS: COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Patient-reported outcome measures in cerebrovascular neurosurgery.

OBJECTIVE: The object of this study was to describe the use of patient-reported outcome measures (PROMs) in cerebrovascular neurosurgery and to outline a framework for incorporating them into future cerebrovascular research. METHODS: Following the standardized PRISMA guidelines, the authors performed a search of the PubMed and Embase databases in February 2023 using filters to investigate six specific cerebrovascular pathologies/procedures: subarachnoid hemorrhage (SAH), intracranial hemorrhage, ischemic stroke, arteriovenous malformation, chronic subdural hematoma, and carotid artery stenosis. PROMs in the identified articles were distinguished and classified as generic, symptom specific, or disease specific. RESULTS: A total of 259 studies including 51 PROMs were eligible for inclusion in the review. Most of the PROMs were generic or symptom specific. Only 5 PROMs were disease specific, and all of these pertained to stroke or SAH. CONCLUSIONS: There are only a limited number of disease-specific PROMs available for cerebrovascular pathologies and outcomes. Further validation of existing measures in independent cohorts, expanded incorporation of disease-specific PROMs in prospective trials, and the development of new PROMs specific to cerebrovascular conditions are critical to a better understanding of the impact of cerebrovascular diseases and novel therapies on patient lives.

Healthcare personnel in 2016-2019 prospective cohort infrequently got vaccinated, worked while ill, and frequently used antibiotics rather than antivirals against viral influenza illnesses.

Background: Uncertainty about risk of illness and the value of influenza vaccines negatively affects vaccine uptake among persons targeted for influenza vaccination. Methods: During 2016-2019, we followed a cohort of healthcare personnel (HCP) targeted for free-of-charge influenza vaccination in five Lima hospitals to quantify risk of influenza, workplace presenteeism (coming to work despite illness), and absenteeism (taking time off from work because of illness). The HCP who developed acute respiratory illnesses (ARI) (≥1 of acute cough, runny nose, body aches, or feverishness) were tested for influenza using reverse-transcription polymerase chain reaction (rt-PCR). Findings: The cohort (2968 HCP) contributed 950,888 person-days. Only 36 (6%) of 605 HCP who participated every year were vaccinated. The HCP had 5750 ARI and 147 rt-PCR-confirmed influenza illnesses. The weighted incidence of laboratory-confirmed influenza was 10.0/100 person-years; 37% used antibiotics, and 0.7% used antivirals to treat these illnesses. The HCP with laboratory-confirmed influenza were present at work while ill for a cumulative 1187 hours. Interpretation: HCP were frequently ill and often worked rather than stayed at home while ill. Our findings suggest the need for continuing medical education about the risk of influenza and benefits of vaccination and stay-at-home-while-ill policies.

Humoral Immune Response to Messenger RNA Coronavirus Disease 2019 Vaccination Among Children Aged 5-11 Years in a Multisite Prospective Cohort Study, September 2021-September 2022.

Background: The PROTECT study is a longitudinal cohort study initiated in July 2021 with weekly testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 4 states: Arizona, Florida, exas, and Utah. This study aims to examine vaccine-elicited antibody response against postvaccination SARS-CoV-2 infections. Methods: Children aged 5-11 years had serum collected 14-59 days after their second dose of monovalent Pfizer-BioNTech coronavirus disease 2019 messenger RNA vaccine. Vaccine-elicited antibodies were measured using the area under the curve (AUC) and end-point titer using enzyme-linked immunosorbent assay (receptor-binding domain [RBD] and S2) and surrogate neutralization assays against ancestral (WA1) and Omicron (BA.2). Results: 79 vaccinated participants (33 [41.7%] female; median age, 8.8 years [standard deviation, 1.9 years]), 48 (60.8%) were from Tucson, Arizona; 64 (81.0%) were non-Hispanic white; 63 (80.8%) attended school in person; 68 (86.1%) did not have any chronic conditions; and 47 (59.5%) were infected after vaccination. Uninfected children had higher AUCs against WA1 (P = .009) and Omicron (P = .02). The geometric mean and surrogate neutralization titer above the limit of detection was 346.0 for WA1 and 39.7 for Omicron, an 8.7-fold decrease (P < .001). After adjustment of covariates in the WA1-specific model, we observed a 47% reduction in the odds of postvaccination infection for every standard deviation increase in RBD AUC (aOR, 0.53 [95% confidence interval, .29-.97) and a 69% reduction in the odds of infection for every 3-fold increase in RBD end titer (0.31 [.06-1.57]). Conclusions: Children with higher antibody levels experienced a lower incidence of postvaccination SARS-CoV-2 infection.

Greater burden of white matter lesions and silent infarcts ipsilateral to carotid stenosis.

OBJECTIVES: Carotid stenosis may cause silent cerebrovascular disease (CVD) through atheroembolism and hypoperfusion. If so, revascularization may slow progression of silent CVD. We aimed to compare the presence and severity of silent CVD to the degree of carotid bifurcation stenosis by cerebral hemisphere. MATERIALS AND METHODS: Patients age ≥40 years with carotid stenosis >50% by carotid ultrasound who underwent MRI brain from 2011-2015 at Mayo Clinic were included. Severity of carotid stenosis was classified by carotid duplex ultrasound as 50-69% (moderate), 70-99% (severe), or occluded. White matter lesion (WML) volume was quantified using an automated deep-learning algorithm applied to axial T2 FLAIR images. Differences in WML volume and prevalent silent infarcts were compared across hemispheres and severity of carotid stenosis. RESULTS: Of the 183 patients, mean age was 71±10 years, and 39.3% were female. Moderate stenosis was present in 35.5%, severe stenosis in 46.5% and occlusion in 18.0%. Patients with carotid stenosis had greater WML volume ipsilateral to the side of carotid stenosis than the contralateral side (mean difference, 0.42±0.21cc, p=0.046). Higher degrees of stenosis were associated with greater hemispheric difference in WML volume (moderate vs. severe; 0.16±0.27cc vs 0.74±0.31cc, p=0.009). Prevalence of silent infarct was 23.5% and was greater on the side of carotid stenosis than the contralateral side (hemispheric difference 8.8%±3.2%, p=0.006). Higher degrees of stenosis were associated with higher burden of silent infarcts (moderate vs severe, 10.8% vs 31.8%; p=0.002). CONCLUSIONS: WML and silent infarcts were greater on the side of severe carotid stenosis.

Nanoparticle approaches for the renin-angiotensin system.

The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1-100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.

Middle meningeal artery embolization with polyvinyl alcohol particles in a patient with ophthalmic artery origin from middle meningeal artery: Case report and technical note.

This is a case report of an adult with chronic subdural hematoma (cSDH) who underwent endovascular treatment for middle meningeal artery (MMA) embolization. There was a prominent meningo-ophthalmic branch with an absence of an ophthalmic artery from the internal carotid artery. MMA embolization was performed utilizing particles with no complications and the resolution of the cSDH was within 4 months. This case report demonstrates that despite extreme variant anatomy, MMA embolization with particles is feasible, effective, and safe when appropriate techniques are used.

Long-Term Follow-up of Multinodular and Vacuolating Neuronal Tumors and Implications for Surveillance Imaging.

BACKGROUND AND PURPOSE: Most multinodular and vacuolating neuronal tumors (MVNTs) are diagnosed and followed radiologically without any change across time. There are no surveillance guidelines or quantitative volumetric assessments of these tumors. We evaluated MVNT volumes during long follow-up periods using segmentation tools with the aim of quantitative assessment. MATERIALS AND METHODS: All patients with MVNTs in a brain MR imaging report in our system were reviewed. Patients with only 1 brain MR imaging or in whom MVNT was not clearly the most likely diagnosis were excluded. All MVNTs were manually segmented. For all follow-up examinations, absolute and percentage volume change from immediately prior and initial examinations were calculated. RESULTS: Forty-eight patients (32 women; median age, 50.5 years at first scanning) underwent 158 brain MRIs. The median duration between the first and last scan was 15.6 months (interquartile range, 5.7-29.6 months; maximum, 6.4 years) and between consecutive scans, it was 6.7 months (interquartile range, 3.3-12.4 months; maximum, 4.9 years). Pearson correlation coefficients between days since immediately prior scan versus absolute and percentage volume change from immediately prior scan were r = 0.05 (P = .60) and r = 0.07 (P = .45), respectively. For the relationship between days since the first scan versus absolute and percentage volume change from the first scan, values were r = -0.06 (P = .53) and r = -0.04 (P = .67), respectively. CONCLUSIONS: MVNT segmentation across follow-up brain MR imaging examinations did not demonstrate significant volume differences, suggesting that these tumors do not enlarge with time. Hence, frequent surveillance imaging of newly diagnosed MVNTs may not be necessary.

The effect of long-term spaceflight on drug potency and the risk of medication failure.

Pharmaceuticals selected for exploration space missions must remain stable and effective throughout mission timeframes. Although there have been six spaceflight drug stability studies, there has not been a comprehensive analytical analysis of these data. We sought to use these studies to quantify the rate of spaceflight drug degradation and the time-dependent probability of drug failure resulting from the loss of active pharmaceutical ingredient (API). Additionally, existing spaceflight drug stability studies were reviewed to identify research gaps to be addressed prior to exploration missions. Data were extracted from the six spaceflight studies to quantify API loss for 36 drug products with long-duration exposure to spaceflight. Medications stored for up to 2.4 years in low Earth orbit (LEO) exhibit a small increase in the rate of API loss with a corresponding increase in risk of product failure. Overall, the potency for all spaceflight-exposed medications remains within 10% of terrestrial lot-matched control with a ~1.5 increase in degradation rate. All existing studies of spaceflight drug stability have focused primarily on repackaged solid oral medications, which is important because non-protective repackaging is a well-established factor contributing to loss of drug potency. The factor most detrimental to drug stability appears to be nonprotective drug repackaging, based on premature failure of drug products in the terrestrial control group. The result of this study supports a critical need to evaluate the effects of current repackaging processes on drug shelf life, and to develop and validate suitable protective repackaging strategies that help assure the stability of medications throughout the full duration of exploration space missions.