Percutaneous Pleural Drainage in Patients Taking Clopidogrel: Real Danger or Phantom Fear?

Despite being categorized as a procedure associated with a low risk of iatrogenic hemorrhage, percutaneous pleural drainage in patients taking the ubiquitous antiplatelet agent clopidogrel is still commonly perceived as a risky proposition. There is mounting evidence, however, in support of the safety of percutaneous needle procedures in persons receiving this medication. Establishing that these pleural interventions can be performed safely without clopidogrel interruption would be of great clinical significance, especially in those taking it for recent cardiac stenting and therefore in danger of stent thrombosis should antiplatelet therapy (APT) be withheld. The purpose of the present review is to summarize the available data from published studies and series of thoracentesis and chest tube insertion in patients exposed to clopidogrel. Also incorporated into this review are relevant investigations from the thoracic surgery and interventional radiology experience, which contribute indirect evidence and help shape the context for interpreting the safety data reported in the pleural literature. At the end, an attempt is made to synthesize the current knowledge on this topic into conclusions for guiding practice

SETBP1 Mutations as a Biomarker for Myelodysplasia /Myeloproliferative Neoplasm Overlap Syndrome

Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1 mutations have been identified in up to 32% of aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients. The mutation hotspot lies in the amino acid residues 858-871 in the SETBP1 protein. SETBP1 mutations in MDS/MPN overlap syndrome is associated with accelerated transformation to leukemia and poor prognosis. In this review, we summarized the latest data on the role of SETBP1 mutations in the overlap syndrome. SETBP1 mutations may serve as a biomarker for the diagnosis and poor prognosis of the overlap syndrome

Complete Remission After Single Agent Blinatumomab in a Patient with Pre-B Acute Lymphoid Leukemia Relapsed and Refractory to Three Prior Regimens: HyperCVAD, High Dose Cytarabine Mitoxantrone and CLAG

BACKGROUND: The current standard of care for relapsed and refractory acute lymphoblastic leukemia (ALL) is combination chemotherapy. CASE PRESENTATION: We report a case of highly refractory ALL who was treated with blinatumomab. The ALL in this patient relapsed within a month after completion of hyperCVAD regimen and was refractory to high dose mitoxantrone/cytarabine and CLAG regimens. CONCLUSION: This highly refractory pre-B Ph(-) ALL was induced to complete remission after one course of single agent blinatumomab

Geochemical characterization of shallow groundwater at the Cranfield aquifer and numerical simulation: Can pH and carbonate parameters be used to detect potential CO2 leakage at geological CO2 sequestration sites?

Bureau of Economic Geolog

Perspectives of patients, family caregivers and health professionals on the use of outcome measures in palliative care and lessons for implementation: a multi-method qualitative study

Background: Routine use of outcome measures in palliative care is recommended to demonstrate and improve quality of care. The use of outcome measures is relatively recent in UK specialist palliative care services and understanding their use in practice is key to successful implementation. We therefore aimed to explore how patient-centred outcome measures are used in specialist palliative care, and identify key considerations for implementation.Methods: Multi-method qualitative study (semi-structured interviews and non-participant observation). Patients, family caregivers and health professionals were purposively sampled from nine specialist palliative care services (hospice, hospital and community settings) in London, UK. Framework analysis, informed by the Consolidated Framework for Implementation Research (CFIR), was undertaken.Results: Thirty eight interviews and nine observations were conducted. Findings are presented according to the five CFIR domains: 1) Intervention: participants highlighted advantages, disadvantages and appropriateness of outcome measures in palliative care; 2) Outer setting: policy and national drivers are necessary to encourage use of outcome measures; 3) Inner setting: information technology infrastructure, organisational drive, and support from peers and leadership were institutional factors that shaped the use of outcome measures; 4) Individual: clear rationale for using outcome measures and skills to use them in practice were essential; 5) Implementation: stepwise introduction of outcome measures, regular feedback sessions, and champions/facilitators were important to strengthen routine use.Conclusion: All CFIR domains need consideration for effective implementation. Outcome data needs to be fed back to and interpreted for professionals in order to improve and sustain outcome data collection, and drive meaningful improvements in palliative care

Nutrient Enrichment Increases Mortality of Mangroves

Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19