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1.
Article in English | MEDLINE | ID: mdl-38858337

ABSTRACT

BACKGROUND: Even though racism is pervasive, some people of color may deny experiencing racial discrimination or may report being unaffected by it. This study examines the contexts and factors that may contribute to these responses among people who use substances. METHODS: We conducted seven focus groups (5-9 participants per group, total N = 43) among Black, Latino, and Asian American adults between the ages of 21 to 44 years old who reported current use of two or more of the following substances: alcohol, cigarettes, e-cigarettes, or cannabis. Data were analyzed using reflexive thematic analysis. RESULTS: Across all three ethno-racial groups, we found some respondents minimized or denied personal experiences of racial discrimination or hesitated to identify their experiences as racial discrimination, which in turn led to respondents to express uncertainty about seeing any sort of connection between racial discrimination and substance use. Themes included a minority comparison effect; a drowning out effect; diversity and racial composition of context; passing as White; and covertness of racism. Also, there were contradictions in accounts, and responses often depended on orienting cues. CONCLUSIONS: While researchers continue to find associations between racial discrimination and substance use, some people of color may not acknowledge this connection. Recommendations include aligning definitions of racism between academic and public/popular discourse; updating measures to keep up with the evolving forms of racism using context-specific examples; combining subjective measures of racial discrimination with objective measures of racism; and dialoguing with the public to raise awareness around how racism is defined.

2.
Sci Adv ; 10(24): eadn9420, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38865455

ABSTRACT

We introduce an information-hiding camera integrated with an electronic decoder that is jointly optimized through deep learning. This system uses a diffractive optical processor, which transforms and hides input images into ordinary-looking patterns that deceive/mislead observers. This information-hiding transformation is valid for infinitely many combinations of secret messages, transformed into ordinary-looking output images through passive light-matter interactions within the diffractive processor. By processing these output patterns, an electronic decoder network accurately reconstructs the original information hidden within the deceptive output. We demonstrated our approach by designing information-hiding diffractive cameras operating under various lighting conditions and noise levels, showing their robustness. We further extended this framework to multispectral operation, allowing the concealment and decoding of multiple images at different wavelengths, performed simultaneously. The feasibility of our framework was also validated experimentally using terahertz radiation. This optical encoder-electronic decoder-based codesign provides a high speed and energy efficient information-hiding camera, offering a powerful solution for visual information security.

3.
J Periodontal Res ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758729

ABSTRACT

Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released by microbes and host cells involved in cell-to-cell communication, found in body biofluids, such as saliva and gingival crevicular fluid (GCF). EVs are mainly involved in cell-to-cell communication, and may hold promise for diagnostic and therapeutic purposes. Periodontal research has examined the potential involvement of bacterial- and host-cell-derived EVs in disease pathogenesis, diagnosis, and therapy, but data remains scarce on immune cell- or microbial-derived EVs. In this narrative review, we first provide an overview of the role of microbial and host-derived EVs on disease pathogenesis. Recent studies reveal that Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans-derived outer membrane vesicles (OMVs) can activate inflammatory cytokine release in host cells, while M1 macrophage EVs may contribute to bone loss. Additionally, we summarised current in vitro and pre-clinical research on the utilisation of immune cell and microbial-derived EVs as potential therapeutic tools in the context of periodontal treatment. Studies indicate that EVs from M2 macrophages and dendritic cells promote bone regeneration in animal models. While bacterial EVs remain underexplored for periodontal therapy, preliminary research suggests that P. gingivalis OMVs hold promise as vaccine candidates. Finally, we acknowledge the current limitations present in the field of translating immune cell derived EVs and microbial derived EVs in periodontology. It is concluded that microbial and host immune cell-derived EVs have a role in periodontitis pathogenesis and hence may be useful for studying disease pathophysiology, and as diagnostic and treatment monitoring biomarkers.

4.
Alzheimers Res Ther ; 16(1): 101, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711159

ABSTRACT

BACKGROUND: In Alzheimer's disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue. METHODS: Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113). RESULTS: Treatment resulted in significant reductions in amyloid-beta (Aß) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice. CONCLUSIONS: This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.


Subject(s)
Alzheimer Disease , Dendrimers , Disease Models, Animal , Mice, Transgenic , Microglia , Plaque, Amyloid , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Microglia/drug effects , Microglia/metabolism , Plaque, Amyloid/drug therapy , Plaque, Amyloid/pathology , Mice , Amyloid beta-Peptides/metabolism , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Humans
5.
ACS Appl Mater Interfaces ; 16(21): 27952-27960, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38808703

ABSTRACT

Capable of directly capturing various physiological signals from human skin, skin-interfaced bioelectronics has emerged as a promising option for human health monitoring. However, the accuracy and reliability of the measured signals can be greatly affected by body movements or skin deformations (e.g., stretching, wrinkling, and compression). This study presents an ultraconformal, motion artifact-free, and multifunctional skin bioelectronic sensing platform fabricated by a simple and user-friendly laser patterning approach for sensing high-quality human physiological data. The highly conductive membrane based on the room-temperature coalesced Ag/Cu@Cu core-shell nanoparticles in a mixed solution of polymers can partially dissolve and locally deform in the presence of water to form conformal contact with the skin. The resulting sensors to capture improved electrophysiological signals upon various skin deformations and other biophysical signals provide an effective means to monitor health conditions and create human-machine interfaces. The highly conductive and stretchable membrane can also be used as interconnects to connect commercial off-the-shelf chips to allow extended functionalities, and the proof-of-concept demonstration is highlighted in an integrated pulse oximeter. The easy-to-remove feature of the resulting device with water further allows the device to be applied on delicate skin, such as the infant and elderly.


Subject(s)
Wearable Electronic Devices , Humans , Skin/chemistry , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Silver/chemistry , Copper/chemistry , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Artifacts , Metal Nanoparticles/chemistry , Motion , Electric Conductivity
6.
J Neurosurg Pediatr ; : 1-7, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38820612

ABSTRACT

OBJECTIVE: The PEDSPINE I and PEDSPINE II scores were developed to determine when patients require advanced imaging to rule out cervical spine injury (CSI) in children younger than 3 years of age with blunt trauma. This study aimed to evaluate these scores in an institutional cohort. METHODS: The authors identified patients younger than 3 years with blunt trauma who received cervical spine MRI from their institution's prospective database from 2012 to 2015. Patient demographics, injury characteristics, and imaging were compared between patients with and without CSI using chi-square and Wilcoxon rank-sum tests. RESULTS: Eighty-eight patients were identified, 8 (9%) of whom had CSI on MRI. The PEDSPINE I system had a higher sensitivity (50% vs 25%) and negative predictive value (93% vs 92%), whereas PEDSPINE II had a higher specificity (91% vs 65%) and positive predictive value (22% vs 13%). Patients with CSI missed by the scores had mild, radiologically significant ligamentous injuries detected on MRI. Both models would have recommended advanced imaging for the patient who required halo-vest fixation (risk profile: no CSI, 81.9%; ligamentous, 10.1%; osseous, 8.0%). PEDSPINE I would have prevented 52 (65%) of 80 uninjured patients from receiving advanced imaging, whereas PEDSPINE II would have prevented 73 (91%). Using PEDSPINE I, 10 uninjured patients (13%) could have avoided intubation for imaging. PEDSPINE II would not have spared any patients intubation. CONCLUSIONS: Current cervical spine clearance algorithms are not sensitive or specific enough to determine the need for advanced imaging in children. However, these scores can be used as a reference in conjunction with physicians' clinical impressions to reduce unnecessary imaging.

7.
J Neurosurg Pediatr ; 34(1): 75-83, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38579347

ABSTRACT

OBJECTIVE: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction. METHODS: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders. RESULTS: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision. CONCLUSIONS: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.


Subject(s)
Emergency Service, Hospital , Humans , Male , Female , Retrospective Studies , Child , Child, Preschool , Infant , Adolescent , Reoperation/statistics & numerical data , Hydrocephalus/surgery , Socioeconomic Factors , Cerebrospinal Fluid Shunts , Equipment Failure
8.
Periodontol 2000 ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647020

ABSTRACT

Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant-bone interface via "biomimicry," a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L-PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L-PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.

9.
Anal Chem ; 96(17): 6746-6755, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38632675

ABSTRACT

Nonionic surfactant excipients (NISEs) are commonly added to biologics formulations to mitigate the effects of stress incurred by the active biotherapeutic during manufacturing, transport, and storage. During manufacturing, NISEs are added by dilution of a stock solution directly into a protein formulation, and their accurate addition is critical in maintaining the quality and integrity of the drug product and thus ensuring patient safety. This is especially true for the common NISEs, polysorbates 20 and 80 (PS20 and PS80, respectively) and poloxamer 188 (P188). With the increasing diversity of biologic modalities within modern pharmaceutical pipelines, there is thus a critical need to develop and deploy convenient and user-accessible analytical techniques that can rapidly and reliably quantify these NISEs under biopharmaceutically relevant conditions. We thus pursued 60 MHz benchtop quantitative NMR (qNMR) as a nondestructive and user-friendly analytical technique for the quantification of PS20, PS80, and P188 under such conditions. We demonstrated the ability of benchtop qNMR (1) to quantify simulated PS20, PS80, and P188 stock solutions representative of those used during the drug substance (DS) formulation step in biomanufacturing and (2) to quantify these NISEs at and below their target concentrations (≤0.025% w/v) directly in biologics formulations containing histidine, sucrose, and one of three biotherapeutic modalities (monoclonal antibody, antibody-drug conjugate, and Fc-fusion protein). Our results demonstrate that benchtop qNMR offers a fit-for-purpose, reliable, user-friendly, and green analytical route by which NISE of interest to the biopharmaceutical industry may be readily and reliably quantified. We conclude that benchtop qNMR has the potential to be applied to other excipient formulation components in the presence of various biological modalities as well as the potential for routine integration within analytical and QC laboratories across pharmaceutical development and manufacturing sites.


Subject(s)
Excipients , Magnetic Resonance Spectroscopy , Surface-Active Agents , Surface-Active Agents/chemistry , Excipients/chemistry , Excipients/analysis , Magnetic Resonance Spectroscopy/methods , Polysorbates/chemistry , Poloxamer/chemistry , Biological Products/chemistry , Biological Products/analysis
10.
World Neurosurg ; 186: e181-e190, 2024 06.
Article in English | MEDLINE | ID: mdl-38537791

ABSTRACT

BACKGROUND: Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes. METHODS: This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed. RESULTS: A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06-2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00-1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00-1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00-1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes. CONCLUSIONS: HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion.


Subject(s)
Ischemic Stroke , Thrombectomy , Humans , Male , Female , Aged , Middle Aged , Ischemic Stroke/surgery , Ischemic Stroke/diagnostic imaging , Retrospective Studies , Thrombectomy/methods , Stroke Rehabilitation/methods , Treatment Outcome , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/surgery , Aged, 80 and over
11.
Int J Mol Sci ; 25(3)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38338647

ABSTRACT

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case-control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions.


Subject(s)
Dry Eye Syndromes , Vascular Endothelial Growth Factor A , Humans , Animals , Mice , Rabbits , Vascular Endothelial Growth Factor A/metabolism , Retrospective Studies , Tears/metabolism , Vascular Endothelial Growth Factors/metabolism , Dry Eye Syndromes/metabolism
12.
Am J Prev Med ; 66(6): 957-962, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38342478

ABSTRACT

INTRODUCTION: The U.S. Food and Drug Administration approved the updated 2023-2024 COVID-19 vaccines by Pfizer-BioNTech and Moderna on September 11, 2023. Despite the Centers for Disease Control and Prevention's recommendation that everyone aged ≥6 years receive the updated COVID-19 vaccine, the general public's intentions to receive the new 2023-2024 vaccine are unknown. METHODS: Intentions to receive the new COVID-19 vaccine and the demographic predictors of those intentions were assessed from a survey of adult residents, aged ≥18 years, of Los Angeles County, California conducted in October 2023. RESULTS: Of the 1,090 participants, 701 (64.3%) indicated they were planning on receiving the new COVID-19 vaccine, 217 (19.9%) responded no, and 172 (15.8%) were unsure. Male gender (versus female); age groups of 50-64 and ≥65 years (versus 18-29 years); and ≥$100,000 household income (versus ≤$49,999) were associated with higher odds of reporting yes than reporting no regarding their vaccination intentions. Asian and Hispanic race/ethnicity (versus Non-Hispanic White) were associated with higher odds of indicating not sure than the odds of indicating no vaccination intentions. A significantly higher proportion of not-sure respondents reported "I plan to wait and see if it is safe and may get it later", whereas a significantly higher proportion of no respondents reported "I don't believe I need a COVID-19 vaccine booster" and "I don't trust COVID-19 vaccines." CONCLUSIONS: This study demonstrates demographic differences in attitudes toward COVID-19 vaccination intentions and highlights the importance of promotional messages and initiatives that target more hesitant populations. These messages should address possible side effects and vaccine safety.


Subject(s)
COVID-19 Vaccines , COVID-19 , Intention , Humans , Male , Female , COVID-19 Vaccines/administration & dosage , Middle Aged , Adult , COVID-19/prevention & control , Adolescent , Young Adult , Aged , Surveys and Questionnaires , SARS-CoV-2 , Vaccination Hesitancy/statistics & numerical data , Vaccination Hesitancy/psychology , Los Angeles , United States , Vaccination/statistics & numerical data , Vaccination/psychology
13.
J Craniofac Surg ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38260961

ABSTRACT

BACKGROUND AND OBJECTIVES: Ventricular shunting is one of the most common procedures in neurosurgery. However, complications and revisions are frequent. Patients requiring multiple revisions often suffer secondary issues with scalp healing over hardware. Many common ventricular shunt valves have an obligate thickness that creates a visible protrusion and can potentially cause local tissue ischemia and breakdown in the setting of repeated surgery. The authors present a simple technique for recessing the shunt valve into the underlying bone to alleviate protrusion in high-risk cases. Three example cases utilizing this technique are presented. METHODS: The skull directly underlying the planned valve site is uniformly recessed with a cutting burr several millimeters as desired while maintaining the inner cortical bone layer. The valve is fixed with standard cranial plating hardware. EXPECTED OUTCOMES: Three patients are reported who underwent shunt valve recession as an adjunct to their shunt revision with neuroplastic surgery assistance. All patients had undergone multiple prior surgeries that had resulted in thin and high-risk fragile scalp. In 1 patient, the prior valve was eroding through the scalp before the described revision. All patients had satisfactory cosmetic outcomes, and there were no revisions in the 2-month follow-up period. DISCUSSION: Complex and high-risk ventricular shunt patients should be considered for shunt valve recession into the bone to reduce wound-related complications and enhance healing. This is a technically simple, safe, and effective technique to include as a neuroplastic adjunct.

15.
Sci Total Environ ; 912: 169120, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38070558

ABSTRACT

Multi-hazard events, characterized by the simultaneous, cascading, or cumulative occurrence of multiple natural hazards, pose a significant threat to human lives and assets. This is primarily due to the cumulative and cascading effects arising from the interplay of various natural hazards across space and time. However, their identification is challenging, which is attributable to the complex nature of natural hazard interactions and the limited availability of multi-hazard observations. This study presents an approach for identifying multi-hazard events during the past 123 years (1900-2023) using the EM-DAT global disaster database. Leveraging the 'associated hazard' information in EM-DAT, multi-hazard events are detected and assessed in relation to their frequency, impact on human lives and assets, and reporting trends. The interactions between various combinations of natural hazard pairs are explored, reclassifying them into four categories: preconditioned/triggering, multivariate, temporally compounding, and spatially compounding multi-hazard events. The results show, globally, approximately 19 % of the 16,535 disasters recorded in EM-DAT can be classified as multi-hazard events. However, the multi-hazard events recorded in EM-DAT are disproportionately responsible for nearly 59 % of the estimated global economic losses. Conversely, single hazard events resulted in higher fatalities compared to multi-hazard events. The largest proportion of multi-hazard events are associated with floods, storms, and earthquakes. Landslides emerge as the predominant secondary hazards within multi-hazard pairs, primarily triggered by floods, storms, and earthquakes, with the majority of multi-hazard events exhibiting preconditioned/triggering and multivariate characteristics. There is a higher prevalence of multi-hazard events in Asia and North America, whilst temporal overlaps of multiple hazards predominate in Europe. These results can be used to increase the integration of multi-hazard thinking in risk assessments, emergency management response plans and mitigation policies at both national and international levels.

16.
Brain Behav Immun ; 116: 160-174, 2024 02.
Article in English | MEDLINE | ID: mdl-38070624

ABSTRACT

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.


Subject(s)
Brain Edema , Ischemic Stroke , Humans , Mice , Animals , Monocytes/metabolism , Brain Edema/metabolism , Programmed Cell Death 1 Receptor/metabolism , B7-H1 Antigen/metabolism , Infarction, Middle Cerebral Artery/metabolism
17.
Eur Radiol ; 34(4): 2394-2404, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37735276

ABSTRACT

OBJECTIVE: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT. METHODS: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, contributed by 95 hospitals and imaging facilities. Grouping exams into deciles by, first, patient size, and second, size-adjusted dose length product (DLP), we summarized dose and technical parameters and estimated which parameters contributed most to between-protocols dose variation. Lastly, we modeled the total population dose if all protocols with mean size-adjusted DLP above 433 or 645 mGy-cm were reduced to these thresholds. RESULTS: A total of 748,846 CTs were performed using 1033 unique protocols. When sorted by patient size, patients with larger abdominal diameters had increased dose and effective mAs (milliampere seconds), even after adjusting for patient size. When sorted by size-adjusted dose, patients in the highest versus the lowest decile in size-adjusted DLP received 6.4 times the average dose (1680 vs 265 mGy-cm) even though diameter was no different (312 vs 309 mm). Effective mAs was 2.1-fold higher, unadjusted CTDIvol 2.9-fold, and phase 2.5-fold for patients in the highest versus lowest size-adjusted DLP decile. There was virtually no change in kV (kilovolt). Automatic exposure control was widely used to modulate mAs, whereas kV modulation was rare. Phase was the strongest driver of between-protocols variation. Broad adoption of optimized protocols could result in total population dose reductions of 18.6-40%. CONCLUSION: There are large variations in radiation doses for routine abdomen CT unrelated to patient size. Modification of kV and single-phase scanning could result in substantial dose reduction. CLINICAL RELEVANCE: Radiation dose-optimization techniques for routine abdomen CT are routinely under-utilized leading to higher doses than needed. Greater modification of technical parameters and number of phases could result in substantial reduction in radiation exposure to patients. KEY POINTS: • Based on an analysis of 748,846 routine abdomen CT scans in adults, radiation doses varied tremendously across patients of the same size and optimization techniques were routinely under-utilized. • The difference in observed dose was due to variation in technical parameters and phase count. Automatic exposure control was commonly used to modify effective mAs, whereas kV was rarely adjusted for patient size. Routine abdomen CT should be performed using a single phase, yet multi-phase was common. • kV modulation by patient size and restriction to a single phase for routine abdomen indications could result in substantial reduction in radiation doses using well-established dose optimization approaches.


Subject(s)
Radiation Exposure , Tomography, X-Ray Computed , Adult , Humans , Radiation Dosage , Retrospective Studies , Tomography, X-Ray Computed/methods , Abdomen
18.
J Am Coll Radiol ; 21(1): 19-26, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37939812

ABSTRACT

OBJECTIVE: To introduce a novel next level of care (NLC) protocol used in our breast imaging practice to bypass additional imaging and image-guided biopsy orders and to examine the impact of NLC on breast biopsy wait times compared with thyroid biopsy wait times, which do not use NLC. METHODS: Our institutional review board deemed this retrospective analysis to be exempt. NLC was implemented for breast imaging in late 2014. Two 6-month periods before and after the COVID-19 shutdown were sampled and compiled. Data were queried from departmental database and electronic health record for all breast and thyroid biopsies during this time. Time to biopsy (TTB) was defined as the number of days from the diagnostic imaging evaluation recommending the biopsy to the completion of the biopsy. To determine the effect of NLC, TTB was compared between breast and thyroid biopsies. RESULTS: Of the 1,114 breast biopsies and 154 thyroid biopsies included, the mean TTB was 9 days (95% confidence interval 8.4-9.3) for breast and 23 days (95% confidence interval 20.5-25.0) for thyroid. There was a 61% reduction in the mean TTB for patients in the breast group compared with patients in the thyroid group. The effect of the NLC was comparable among different races and ethnicities in the breast group, but a significantly higher mean TTB (24% higher, P = .025) was observed for thyroid biopsies in Black patients compared with thyroid biopsies in Hispanic patients. CONCLUSION: NLC protocol facilitates imaging evaluations and reduces the time interval to image-guided biopsies.


Subject(s)
Breast Neoplasms , Radiology , Humans , Female , Retrospective Studies , Radiography , Image-Guided Biopsy/methods , Health Services Accessibility
20.
World Neurosurg ; 183: e495-e501, 2024 03.
Article in English | MEDLINE | ID: mdl-38159607

ABSTRACT

OBJECTIVE: A direct-aspiration first-pass technique (ADAPT) in mechanical thrombectomy has been described in recent studies as an efficacious strategy compared with using a stent retriever (SR). We sought to evaluate for cost differences of ADAPT technique versus SR as an initial approach. METHODS: We conducted a retrospective analysis of consecutive patients with mechanical thrombectomy at our institution between 2022 and 2023. Patients were grouped into ADAPT with/without SR as a rescue strategy and SR as an initial approach with allowance of concomitant aspiration. Direct cost data (consumables) were obtained. Baseline demographics, stroke metrics, procedure outcomes and cost, and last follow-up outcomes in modified Rankin Scale were compared between 2 groups. RESULTS: Fifty-six patients were included. Thirty-seven (66.1%) underwent ADAPT, with 11 (29.7%) eventually requiring an SR. Mean age was 64.8 years. The average National Institutes of Health Stroke Scale score was 13.2 in the ADAPT group and 14.0 in the SR group (P = 0.68), with a similar proportion of tissue plasminogen activator (P = 0.53), site of occlusion (P = 0.66), and tandem occlusion (P = 0.69) between the groups. Recanalization was achieved in 94.6% of all patients, with an average of 1.9 passes, 89.3% being TICI 2B or above, with no differences between the 2 groups. Significantly lower cost (P < 0.01) was observed in ADAPT ($14,243.4) compared with SR ($19,003.6). Average follow-up duration was 180.2 days, with mortality of 23.2%. At last follow-up, 55.4% remained functionally independent (modified Rankin Scale score <3) with no difference (P = 0.56) between the ADAPT (59.5%) and SR (47.4%) groups. CONCLUSIONS: Outcomes were comparable between the ADAPT and SR groups. ADAPT reduced procedural consumables cost by approximately $5000 (25%), even if stent retrievers were allowed to be used for rescue. Establishing ADPAT as initial approach may bring significant direct cost savings while obtaining similar outcomes.


Subject(s)
Brain Ischemia , Stroke , Humans , Middle Aged , Tissue Plasminogen Activator , Retrospective Studies , Cost-Benefit Analysis , Thrombectomy/methods , Treatment Outcome , Stroke/surgery , Stents
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