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1.
Article in English | MEDLINE | ID: mdl-39254809

ABSTRACT

Mobile monitoring provides high-resolution observation on temporal and spatial scales compared to traditional fixed-site measurement. This study demonstrates the use of high spatio-temporal resolution of air pollution data collected by Google Air View vehicles to identify hotspots and assess compliance with WHO Air Quality Guidelines (AQGs) in Dublin City. The mobile monitoring was conducted during weekdays, typically from 7:00 to 19:00, between 6 May 2021 and 6 May 2022. One-second data were aggregated to 377,113 8 s road segments, and 8 s rolling medians were aggregated to hourly and daily levels for further analysis. We assessed the temporal variability of fine particulate matter (PM2.5), nitrogen monoxide (NO), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and carbon dioxide (CO2) concentrations at hyperlocal levels. The average daytime median concentrations of NO2 (28.4 ± 15.7 µg/m3) and PM2.5 (7.6 ± 4.7 µg/m3) exceeded the WHO twenty-four hours (24 h) Air Quality Guidelines in 49.4% and 9% of the 1-year sampling time, respectively. For the diurnal variation of measured pollutants, the morning (8:00) and early evening (18:00) showed higher concentrations for NO2 and PM2.5, mostly happening in the winter season, while the afternoon is the least polluted time except for O3. The low-percentile approach along with 1-h and daytime minima method allowed for decomposing pollutant time series into the background and local contributions. Background contributions for NO2 and PM2.5 changed along with the seasonal variation. Local contributions for PM2.5 changed slightly; however, NO2 showed significant diurnal and seasonal variability related to traffic emissions. Short-lived event enhancement (1 min to 1 h) accounts for 36.0-40.6% and 20.8-42.2% of the total concentration for NO2 and PM2.5. The highly polluted days account for 56.3% of total NO2, highlighting local traffic is the dominant contributor to short-term NO2 concentrations. The longer-lived events (> 8 h) enhancement accounts for 25% of the monitored concentrations. Additionally, conducting optimal hotspot analysis enables mapping the spatial distribution of "hot" spots for PM2.5 and NO2 on highly polluted days. Overall, this investigation suggests both background and local emissions contribute to PM2.5 and NO2 pollution in urban areas and emphasize the urgent need for mitigating NO2 from traffic pollution in Dublin.

3.
PLoS Pathog ; 20(8): e1012436, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39196893

ABSTRACT

Viruses capable of causing persistent infection have developed sophisticated mechanisms for evading host immunity, and understanding these processes can reveal novel features of the host immune system. One such virus, human pegivirus (HPgV), infects ~15% of the global human population, but little is known about its biology beyond the fact that it does not cause overt disease. We passaged a pegivirus isolate of feral brown rats (RPgV) in immunodeficient laboratory mice to develop a mouse-adapted virus (maPgV) that established persistent high-titer infection in a majority of wild-type laboratory mice. maRPgV viremia was detected in the blood of mice for >300 days without apparent disease, closely recapitulating the hallmarks of HPgV infection in humans. We found a pro-viral role for type-I interferon in chronic infection; a lack of PD-1-mediated tolerance to PgV infection; and multiple mechanisms by which PgV immunity can be achieved by an immunocompetent host. These data indicate that the PgV immune evasion strategy has aspects that are both common and unique among persistent viral infections. The creation of maPgV represents the first PgV infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of this persistent RNA virus infections.


Subject(s)
Flaviviridae Infections , Flaviviridae , Animals , Mice , Flaviviridae Infections/virology , Flaviviridae Infections/immunology , Flaviviridae/genetics , Flaviviridae/immunology , Persistent Infection/immunology , Persistent Infection/virology , Rats , Immune Evasion , Mice, Inbred C57BL , Humans
4.
J Soc Cardiovasc Angiogr Interv ; 3(3Part A): 101307, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39131784

ABSTRACT

Background: Mechanical thrombectomy is a promising treatment option for deep vein thrombosis; however, long-term data are lacking. Here, we report for the first time the 1-year clinical outcomes from the completely enrolled ClotTriever Outcomes (CLOUT) registry evaluating mechanical thrombectomy with the ClotTriever System (Inari Medical). Methods: The CLOUT registry (NCT03575364) is a prospective, multicenter, single-arm study that enrolled 500 patients with proximal lower extremity deep vein thrombosis. Prespecified 1-year outcomes include Villalta score and corresponding postthrombotic syndrome (PTS) severity, duplex ultrasound findings of patency (defined as the presence of flow with normal or partial compressibility), Revised Venous Clinical Severity Score, and quality of life (QoL). Results: In CLOUT, the median age was 61.9 years and 50.5% of patients were women. A total of 310 patients completed the 1-year visit. The 1-year PTS rate (Villalta score ≥ 5) was 19.3% and the moderate-to-severe PTS rate (Villalta score ≥ 10) was 8.8%. Median Villalta score decreased from 9.0 (IQR, 5.0-14.0) at baseline to 1.0 (IQR, 0.0-4.0) at 1 year (P < .0001). Similar rates of PTS and moderate-to-severe PTS were observed among limbs assessed at all study time points. Patency was observed in 94.2% of limbs. Median Revised Venous Clinical Severity Score was 6.0 (IQR, 3.0-9.0) at baseline and 3.0 (IQR, 1.0-4.0) at 1 year (P < .0001). Additionally, 90.4% of patients experienced improvements in QoL. Conclusions: One-year outcomes from the CLOUT registry demonstrate low PTS rates and preserved patency accompanied by improved symptom relief and QoL. Study follow-up through 2 years is ongoing.

5.
Article in English | MEDLINE | ID: mdl-39168761

ABSTRACT

BACKGROUND: Large bore percutaneous access is becoming increasingly common. Parallel to this, we observe an increase in vascular access site complications such as bleeding, dissection, thrombosis or pseudo-aneurysms. This study was aimed to evaluate safety and efficacy of covered stent grafts for fixing large bore vascular access injuries. METHODS: A total of 147 Viabahn or Viabahn VBX (WL Gore) stent grafts which were placed across the inguinal ligament in emergent settings in 136 patients, were retrospectively analyzed. The two endpoints were the technical success rate, defined by complete arterial repair, and long-term stent graft patency. We also looked at the need for open conversion, wound infections, and in hospital and 30-day mortality. We followed the patients using duplex ultrasound and computed tomography angiogram to assess for arterial patency, freedom from intervention, stent kinking and clinical symptoms. RESULTS: 30 Viabahn and 117 Viabahn VBX (WL Gore) stent grafts were placed in the distal external iliac artery and into the proximal common femoral artery of 136 patients. Indications for intervention were bleeding in 92 patients (68 %), flow limiting dissection in 41 patients (30 %) and symptomatic AVF in 3 patients (2 %). Primary technical success rate was 100 %. Limited 3-year follow up (101/136 patients) showed 99 % patency with no evidence of stent fracture, stenosis or kinking except in one patient who needed target lesion revascularization due to neointimal hyperplasia. CONCLUSIONS: Covered stent grafts can be placed safely, efficiently, and effectively in the distal external iliac and common femoral arteries across the inguinal ligament. These stent grafts can be used as an alternative therapeutic option to open surgery in patients with large bore vascular access injuries.

6.
iScience ; 27(8): 110525, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39156641

ABSTRACT

Elevated pernio incidence was observed during the COVID-19 pandemic. This prospective study enrolled subjects with pandemic-associated pernio in Wisconsin and Switzerland. Because pernio is a cutaneous manifestation of the interferonopathies, and type I interferon (IFN-I) immunity is critical to COVID-19 recovery, we tested the hypothesis that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated IFN-I signaling might underlie some pernio cases. Tissue-level IFN-I activity and plasmacytoid dendritic cell infiltrates were demonstrated in 100% of the Wisconsin cases. Across both cohorts, sparse SARS-CoV-2 RNA was captured in 25% (6/22) of biopsies, all with high inflammation. Affected patients lacked adaptive immunity to SARS-CoV-2. A hamster model of intranasal SARS-CoV-2 infection was used as a proof-of-principle experiment: RNA was detected in lungs and toes with IFN-I activity at both the sites, while replicating virus was found only in the lung. These data support a viral trigger for some pernio cases, where sustained local IFN-I activity can be triggered in the absence of seroconversion.

7.
Phlebology ; : 2683555241260926, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046331

ABSTRACT

BACKGROUND: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. OBJECTIVES: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. METHODS: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. RESULTS: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. CONCLUSION: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy.

8.
Nat Med ; 30(7): 1905-1912, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38956197

ABSTRACT

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.


Subject(s)
Neoplasms , Whole Genome Sequencing , Humans , Neoplasms/genetics , Neoplasms/therapy , Neoplasms/diagnosis , Child , Male , Child, Preschool , Female , Adolescent , Infant , Genetic Testing/methods , Genome, Human/genetics , Genomics/methods , Infant, Newborn
9.
Nat Commun ; 15(1): 5658, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969634

ABSTRACT

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.


Subject(s)
Disease Models, Animal , Genetic Variation , Macaca mulatta , Animals , Macaca mulatta/genetics , Humans , Gene Frequency , Optic Atrophy, Autosomal Dominant/genetics , Polymorphism, Single Nucleotide , Phenotype , Machine Learning , Genotype , Mutation, Missense
10.
Phlebology ; : 2683555241259616, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38863409

ABSTRACT

OBJECTIVE: To review the current approaches to the diagnosis of Post-Thrombotic Syndrome (PTS) and to evaluate the potential need for a diagnostic tool. METHOD: Medical specialists were invited to participate in an online survey of their current approaches to the diagnosis and management of PTS, including the use of scoring systems, diagnostic imaging techniques and the extent the practitioner reviews the patient's venous history. RESULTS: 502 participants completed the survey. Over 80% obtained imaging reports to confirm a history of deep vein thrombosis (DVT). 72% of participants always obtained an up-to-date duplex ultrasound for PTS diagnosis. Over 50% did not use a scoring system for either PTS diagnosis or management. 65% of the participants agreed that a new system for PTS diagnosis should be devised. CONCLUSION: Heterogeneity was observed in methods of diagnosing PTS by medical practitioners with frequent use of medical imaging studies and moderate use of scoring systems. Development of a new diagnostic tool for PTS should be considered for future studies.

11.
bioRxiv ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38853987

ABSTRACT

Infection with clade I Mpox virus (MPXV) results in adverse pregnancy outcomes, yet the potential for vertical transmission resulting in fetal harm with clade IIb MPXV, the clade that is currently circulating in the Western Hemisphere, remains unknown. We established a rhesus macaque model of vertical MPXV transmission with early gestation inoculation. Three pregnant rhesus macaques were inoculated intradermally with 1.5 × 10^5 plaque forming units (PFU) of clade IIb MPXV near gestational day (GD) 30 and animals were monitored for viremia and maternal and fetal well-being. Animals were euthanized to collect tissues at 5, 14, or 25 days post-inoculation (dpi). Tissues were evaluated for viral DNA (vDNA) loads, infectious virus titers, histopathology, MPXV mRNA and protein localization, as well as MPXV protein co-localization with placental cells including, Hofbauer cells, mesenchymal stromal cells, endothelial cells, and trophoblasts. vDNA was detected in maternal blood and skin lesions by 5 dpi. Lack of fetal heartbeat was observed at 14 or 25 dpi for two dams indicating fetal demise; the third dam developed significant vaginal bleeding at 5 dpi and was deemed an impending miscarriage. vDNA was detected in placental and fetal tissue in both fetal demise cases. MPXV localized to placental villi by ISH and IHC. Clade IIb MPXV infection in pregnant rhesus macaques results in vertical transmission to the fetus and adverse pregnancy outcomes, like clade I MPXV. Further studies are needed to determine whether antiviral therapy with tecovirimat will prevent vertical transmission and improve pregnancy outcomes. One Sentence Summary: Clade IIb Mpox virus infection of pregnant rhesus macaques results in vertical transmission from mother to fetus and adverse pregnancy outcomes.

12.
Sci Total Environ ; 943: 173649, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38852865

ABSTRACT

This research builds upon a previous study that explored the potential of the modified WIBS-4+ to selectively differentiate and detect different bioaerosol classes. The current work evaluates the influence of meteorological and air quality parameters on bioaerosol concentrations, specifically pollen and fungal spore dynamics. Temperature was found to be the most influential parameter in terms of pollen production and release, showing a strong positive correlation. Wind data analysis provided insights into the potential geographic origins of pollen and fungal spore concentrations. Fungal spores were primarily shown to originate from a westerly direction, corresponding to agricultural land use, whereas pollen largely originated from a North-easterly direction, corresponding to several forests. The influence of air quality was also analysed to understand its potential impact on the WIBS fluorescent parameters investigated. Most parameters had a negative association with fungal spore concentrations, whereas several anthropogenic influences showed notable positive correlations with daily pollen concentrations. This is attributed to similar driving forces (meteorological parameters) and geographical origins. In addition, the WIBS showed a significant correlation with anthropogenic pollutants originating from combustion sources, suggesting the potential for such modified spectroscopic instruments to be utilized as air quality monitors. By combining all meteorological and pollution data along with WIBS-4+ channel data, a set of Multiple Linear Regression (MLR) analyses were completed. Successful results with R2 values ranging from 0.6 to 0.8 were recorded. The inclusion of meteorological parameters was dependent on the spore or pollen type being examined.


Subject(s)
Aerosols , Air Pollutants , Environmental Monitoring , Pollen , Spores, Fungal , Environmental Monitoring/methods , Aerosols/analysis , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Air Microbiology , Wind , Spectrum Analysis/methods
13.
Eur Heart J ; 45(19): 1753-1764, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38753456

ABSTRACT

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.


Subject(s)
Carotid Artery Diseases , Positron-Emission Tomography , Stress Disorders, Post-Traumatic , Humans , Female , Male , Adult , Stress Disorders, Post-Traumatic/physiopathology , Stress Disorders, Post-Traumatic/diagnostic imaging , Carotid Artery Diseases/physiopathology , Carotid Artery Diseases/diagnostic imaging , Fluorodeoxyglucose F18 , Magnetic Resonance Imaging , Middle Aged , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Amygdala/diagnostic imaging , Amygdala/physiopathology , Radiopharmaceuticals , Case-Control Studies , Stress, Psychological/physiopathology , Stress, Psychological/complications
14.
Sci Total Environ ; 934: 172963, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38705300

ABSTRACT

The prevalence in allergic diseases has increased considerably in the past decades. An important trigger of the symptoms of allergic rhinitis (hay fever) is the pollen of wind-pollinating plants. This pollen is developed by plants and is released into the air where it gets exposed to environmental influences and air pollution. We investigated the chemical changes to pollen that occur after release from the flower in a rural (Veluwe) and an urban (Amsterdam) site in the Netherlands using Fourier Transform Infrared (FTIR) spectroscopy. During the spring/summer of 2020 (during the COVID pandemic) the pollen of nine taxa (Alnus, Betula, Fagus, Fraxinus, Pinus, Plantago, Poaceae, Quercus and Salix) were collected directly from flowers and the air (using a mobile sampler). FTIR spectra were obtained for multiple individual pollen grains for each taxa. The spectra obtained from airborne pollen collected at the rural vs. urban sites did not show any statistical difference. This is possibly a result of a reduced difference in pollutant concentrations between the two sites due to the COVID-19-lockdown measures were in place. However, consistent differences in the FTIR spectra recovered from airborne vs. flower pollen were recorded for all pollen taxa. After the release from the flower the chemical composition of the pollen changed: (i) polysaccharides are converted to monosaccharides; (ii) protein concentration and/or nitration/oxidation level is altered; (iii) lipids are modified and/or reduced in concentration. These changes may alter the allergenicity of the pollen and suggest that further work on the allergenic nature of airborne pollen is required.


Subject(s)
Air Pollutants , Air Pollution , Allergens , Environmental Monitoring , Flowers , Pollen , Netherlands , Allergens/analysis , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Spectroscopy, Fourier Transform Infrared , COVID-19
15.
J Immunol ; 212(11): 1754-1765, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38639635

ABSTRACT

Mauritian-origin cynomolgus macaques (MCMs) serve as a powerful nonhuman primate model in biomedical research due to their unique genetic homogeneity, which simplifies experimental designs. Despite their extensive use, a comprehensive understanding of crucial immune-regulating gene families, particularly killer Ig-like receptors (KIR) and NK group 2 (NKG2), has been hindered by the lack of detailed genomic reference assemblies. In this study, we employ advanced long-read sequencing techniques to completely assemble eight KIR and seven NKG2 genomic haplotypes, providing an extensive insight into the structural and allelic diversity of these immunoregulatory gene clusters. Leveraging these genomic resources, we prototype a strategy for genotyping KIR and NKG2 using short-read, whole-exome capture data, illustrating the potential for cost-effective multilocus genotyping at colony scale. These results mark a significant enhancement for biomedical research in MCMs and underscore the feasibility of broad-scale genetic investigations.


Subject(s)
Haplotypes , Macaca fascicularis , Receptors, KIR , Animals , Receptors, KIR/genetics , Macaca fascicularis/genetics , NK Cell Lectin-Like Receptor Subfamily C/genetics , Genomics/methods , Genotype
17.
J Comp Eff Res ; 13(6): e240025, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606556

ABSTRACT

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.


Subject(s)
Drug-Eluting Stents , Femoral Artery , Paclitaxel , Peripheral Arterial Disease , Popliteal Artery , Humans , Drug-Eluting Stents/economics , Popliteal Artery/surgery , Peripheral Arterial Disease/economics , Peripheral Arterial Disease/therapy , Femoral Artery/surgery , Male , Female , Aged , Paclitaxel/therapeutic use , Paclitaxel/economics , Paclitaxel/administration & dosage , Time Factors , Middle Aged , Polymers/therapeutic use , Alloys/economics , Cost-Benefit Analysis , Cost Savings
19.
Emerg Infect Dis ; 30(4): 721-731, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38526136

ABSTRACT

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.


Subject(s)
Arterivirus , Animals , Mice , Arterivirus/genetics , Macaca , Macrophages , Cell Line
20.
Lancet Microbe ; 5(4): e335-e344, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484748

ABSTRACT

BACKGROUND: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time. METHODS: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022. To determine the source of WI-CL-001, we systematically sampled wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers. Viral concentrations in wastewater samples over time were measured by RT digital PCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus's host species, we also sequenced SARS-CoV-2 spike receptor binding domains, and, where possible, whole viral genomes to identify and characterise the evolution of this lineage. FINDINGS: We traced WI-CL-001 to its source at a single commercial building. There we detected the cryptic lineage at concentrations as high as 2·7 × 109 genome copies per L. The majority of 12s rRNA sequences detected in wastewater leaving the identified source building were human. Additionally, we generated over 100 viral receptor binding domain and whole-genome sequences from wastewater samples containing the cryptic lineage collected over the 13 consecutive months this virus was detectable (January, 2022, to January, 2023). These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October, 2020, to February, 2021. Despite this, mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants. INTERPRETATION: We propose that prolonged detection of WI-CL-001 in wastewater indicates persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent omicron-like mutations in WI-CL-001's ancestral B.1.234 genome probably reflects persistent infection and extensive within-host evolution. People who shed cryptic lineages could be an important source of highly divergent viruses that sporadically emerge and spread. FUNDING: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention, National Institute on Drug Abuse, and the Center for Research on Influenza Pathogenesis and Transmission.


Subject(s)
COVID-19 , Wastewater , United States , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , Centers for Disease Control and Prevention, U.S.
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