INTRODUCTION:All-cause mortality in patients after repair of aortic aneurysms of the descending thoracic aorta thoracic endovascular aortic repair (TEVAR) is relatively high at mid-term follow-up. ...The aim of this study was to derive and validate a system that could predict all-cause mortality after TEVAR to aid with patient selection.
METHODS:The MOTHER database contained 625 patients that underwent elective surgery for descending thoracic aortic aneurysms. Univariate analysis identified preoperative factors associated with mid-term all-cause mortality, and a Cox proportional hazards model was developed. The model was internally validated using Kaplan-Meier comparison of observed vs predicted mortality. External validation was performed using a data set from the University of Florida College of Medicine.
RESULTS:There were 625 patients that underwent TEVAR for descending thoracic aortic aneurysm in the MOTHER database and 231 in the University of Florida College of Medicine validation set. The mid-term mortality rate at 6 years of follow-up was 34.4% and 34%, respectively. The all-cause mortality risk score was calculated using 0.0398 × (age) + 0.516 × (renal insufficiency) + 0.46 × (previous cerebrovascular disease) + 0.352 × (prior tobacco use) + 0.376 × (number of devices >2) + 0.016 × (maximum aneurysm diameter). Using this score, low-, medium-, and high-risk groups were defined, with predicted survival at 5 years of 80%, 60%, and 40%. Patients at high risk of mid-term all-cause death were identified in the validation cohort using the prediction rule.
CONCLUSIONS:Identifying patients with a limited life expectancy after TEVAR is possible using a preoperative risk-stratification system. This information can be used to inform decision making regarding when and whether to proceed with TEVAR.
Deep vein thromboses (DVTs) cause significant morbidity and mortality in the general population. Oral anticoagulation therapy may reduce thrombus propagation but does not cause clot lysis and ...therefore does not prevent postthrombotic syndrome (PTS). Catheter-directed thrombolysis (CDT) can be used to treat DVTs as an adjunct to medical therapy, but there is no consensus defining exact indications. Current evidence suggests that CDT can reduce clot burden and DVT recurrence and consequently prevents the formation of PTS compared with systemic anticoagulation. Appropriate indications include younger individuals with acute proximal thromboses, a long life expectancy, and relatively few comorbidities. Limb-threatening thromboses may also be treated with CDT, although the subsequent mortality remains high. A number of randomized controlled trials are currently under way comparing the longer-term outcomes of CDT compared with anticoagulation alone. Initial reports suggest that venous patency and valvular function are better maintained after CDT. The effectiveness of combined pharmacomechanical thrombectomy and the role of vena cava filters need to be investigated further before strong recommendations can be made. The reported short-term outcomes following catheter-based intervention for DVT are encouraging in selected patients. Further evidence is required to establish long-term benefits and cost-effectiveness.
Abstract
The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for ...a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.
BackgroundBiological tissues are composed of heterogeneous cell populations intricately organized in 3D architectures. However, cell type composition and their spatial organization remain largely ...uncharacterized for most tissue types. Although single-cell sequencing analysis provides a systematic and quantitative approach to resolve cell type composition, the cell-cell interactions and cellular organization that define unique tissues are lost due to the requirement of cell dissociation for this approach. Spatial information is critical to better understand the spatiotemporal complexities of diseases such as cancer. Recently, spatially resolved, single-cell transcriptomic imaging platforms have provided a necessary solution to bridge this spatial information gap. The Vizgen® MERSCOPE® Platform, built on multiplexed error robust fluorescence in situ hybridization (MERFISH) technology, enables the direct profiling of the spatial distribution of hundreds of RNA species in intact tissue with subcellular resolution.MethodsHere, we demonstrate the power of MERSCOPE in combination with our Predesigned Immuno-Oncology Panel to characterize the immunological landscape of various human malignant tumor tissue samples. Using this 500-gene immune-oncology panel to characterize canonical signaling pathways of cancer and immune response within the tumor microenvironment, we spatially profiled gene expression across 16 human tumor samples, including breast, colon, prostate, liver, ovarian, lung, uterine, and skin cancer.ResultsTo demonstrate the capability of our immune-oncology panel to characterize many types of malignant tumor tissues, we clustered each MERFISH dataset. Then we annotated the combined clusters of all datasets to create a comprehensive cancer cell atlas. This unified characterization of the tested tumors revealed the presence of B and T cell populations in most of the malignancies tested. To further analyze the heterogeneity present within these critical immune cell populations, we combined spatial autocorrelation and gene expression clustering to subcluster the pan-sample populations of B and T cells. Using the spatial information embedded in our MERSCOPE data, we identified the tissue neighborhoods of these immune subtypes and further compared the neighborhoods between different B and T cell subtypes in the various cancer tumors tested.ConclusionsThis analysis elucidated different patterns of immune cell localization related to immune hubs and the tumor-immune interface, as well as gene expression differences relating to inflammation and immune activation. These findings demonstrate the power of the MERSCOPE Platform and Vizgen Predesigned Panels for immune profiling in the tumor microenvironment.
Open surgery is widely used as a benchmark for the results of fenestrated endovascular repair of complex abdominal aortic aneurysms (AAA). However, the existing evidence stems from single-centre ...experiences, and may not be reproducible in wider practice. National outcomes provide valuable information regarding the safety of suprarenal aneurysm repair.
Demographic and clinical data were extracted from English Hospital Episodes Statistics for patients undergoing elective suprarenal aneurysm repair from 1 April 2000 to 31 March 2010. Thirty-day mortality and five-year survival were analysed by logistic regression and Cox proportional hazards modeling.
793 patients underwent surgery with 14% overall 30-day mortality, which did not improve over the study period. Independent predictors of 30-day mortality included age, renal disease and previous myocardial infarction. 5-year survival was independently reduced by age, renal disease, liver disease, chronic pulmonary disease, and known metastatic solid tumour. There was significant regional variation in both 30-day mortality and 5-year survival after risk-adjustment. Regional differences in outcome were eliminated in a sensitivity analysis for perioperative outcome, conducted by restricting analysis to survivors of the first 30 days after surgery.
Elective suprarenal aneurysm repair was associated with considerable mortality and significant regional variation across England. These data provide a benchmark to assess the efficacy of complex endovascular repair of supra-renal aneurysms, though cautious interpretation is required due to the lack of information regarding aneurysm morphology. More detailed study is required, ideally through the mandatory submission of data to a national registry of suprarenal aneurysm repair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in ...bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB. Notably, TB diagnosis is based on clinical symptoms and sputum laboratory findings. This is despite the fact that approximately half of all patients commencing TB treatment are sputum-negative, resulting in a high proportion of presumptive treatments. Here, we propose to use a sensitive air sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects, at the same time evaluating the potential to identify unrecognized transmitters of TB.
Our parallel-group design will identify viable Mtb in bioaerosols produced by individuals attending a TB clinic in South Africa. Sampling will be performed on eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive. Participants will be prospectively classified into three distinct groups based on National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling following a specific respiratory manoeuvre; and (2) indirect sampling during passive respiratory activity. Bioaerosol specimens will be analyzed for viable Mtb using DMN-trehalose staining and live-cell fluorescence microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the groups. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status and current isoniazid preventive therapy (IPT) use; we will also determine the impact of anti-TB chemotherapy on Mtb-containing bioaerosol production.
Respiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring.
ClinicalTrials.gov: NCT04241809 . Date of Registration: 27/1/2020.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Short Stay EVAR is Safe and Cost Effective Shaw, Sarah E.; Preece, Ryan; Stenson, Katherine M. ...
European journal of vascular and endovascular surgery,
March 2019, 2019-Mar, 2019-03-00, 20190301, Letnik:
57, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Reducing length of stay (LOS) following surgery offers the potential to improve resource utilisation. Endovascular aneurysm repair (EVAR) is now delivered with a low level of morbidity and as such ...may be deliverable as a “23 hour stay” intervention. This systematic review aims to assess safety, feasibility and cost effectiveness of a short stay EVAR pathway.
A database search of Ovid MEDLINE (1996 – April 2018) and Embase (1974 – April 2018) was completed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. A Newcastle–Ottawa Scale was applied to assess study bias.
In total, 570 papers were identified through the literature search, of which 32 abstracts were screened. This led to nine papers being assessed for eligibility. From five suitable studies, 450 (75%) patients were successfully discharged the same or next day after EVAR. Complications most often occurred within 3 hours of surgery, and major complications requiring intensive treatment unit admission occurred within 6 hours. Readmission rates were 0–5% for those discharged early, with no difference in 30 day readmission. Early discharge led to a statistically significant cost saving of £13,360 (LOS four days) to £9844 (LOS one day).
Selected patients can safely undergo EVAR using a short stay pathway. A period of monitoring 6 h post-operatively for low risk patients would be sufficient. Reducing length of stay after EVAR in the UK from the current median of three days to 1.5 days would free 4361 bed days and lead to a saving of approximately £1,800,000 annually.
SUMMARY POINTS Aortic dissection is diagnosed and managed according to its anatomical extent and chronicity White men aged over 40 years with hypertension, or those under 40 with Marfan's syndrome or ...bicuspid aortic valves, are at highest risk Patients often present with acute onset sharp chest pain, sometimes with loss of consciousness or poor perfusion of end organs Computed tomography aortography is the first line diagnostic investigation, followed by transoesophageal echocardiography; magnetic resonance angiography is preferred for surveillance Manage proximal (type A) dissection surgically if possible Uncomplicated distal (type B) dissection is best managed with intensive drug treatment; complicated type B dissection requires surgical intervention All patients need lifelong antihypertensive therapy and surveillance imaging
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