ABSTRACT
The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.
Subject(s)
Pulmonary Embolism , Thrombectomy , Humans , Thrombectomy/adverse effects , Pulmonary Embolism/drug therapy , Thrombolytic Therapy/methods , Acute Disease , Retrospective Studies , Anticoagulants/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Consultation of specialty palliative care remains uncommon in pediatric stem cell transplant (SCT) despite growing evidence that early integration of palliative care improves outcomes in patients with advanced cancers or undergoing SCT. Little is known about how multidisciplinary pediatric SCT teams perceive palliative care and its role in SCT. PROCEDURE: We conducted semistructured interviews of members of a multi-disciplinary SCT team to understand their perceptions of palliative care, how specialty palliative care is integrated into SCT, and to identify barriers to increased integration. Eligible participants included physicians, nurses, inpatient nurse practitioners, social workers, and child life specialists. Data were analyzed using thematic analysis. RESULTS: Four major themes were identified. First, SCT team members held a favorable perception of the palliative care team. Second, participants desired increased palliative care integration in SCT. Third, participants believed that the palliative care team had insufficient resources to care for the large number of SCT patients, which led to the SCT team limiting palliative care consultation. And, finally, the lack of a standardized palliative care consultation process prevented greater integration of palliative care in SCT. CONCLUSIONS: SCT team members held a favorable perception of palliative care and saw a role for greater palliative care integration throughout the SCT course. We identified modifiable barriers to greater palliative care integration. SCT teams who desire greater palliative care integration may adapt and implement an existing model of palliative care integration in order to improve standardization and increase integration of specialty palliative care in SCT.
Subject(s)
Attitude of Health Personnel , Palliative Care , Child , Humans , Qualitative Research , Referral and Consultation , Stem Cell TransplantationABSTRACT
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis. Here we demonstrate that two mouse NLRP1 paralogs (NLRP1AB6 and NLRP1BB6) are also activated by N-terminal proteolytic cleavage. We also demonstrate that proteolysis within a specific N-terminal linker region is sufficient to activate human NLRP1. Evolutionary analysis of primate NLRP1 shows the linker/cleavage region has evolved under positive selection, indicative of pathogen-induced selective pressure. Collectively, these results identify proteolysis as a general mechanism of NLRP1 inflammasome activation that appears to be contributing to the rapid evolution of NLRP1 in rodents and primates.
Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/immunology , Apoptosis Regulatory Proteins/metabolism , Inflammasomes/immunology , Inflammasomes/metabolism , Animals , HEK293 Cells , Humans , Immunoblotting , Mice , NLR Proteins , Polymerase Chain Reaction , Proteolysis , TransfectionABSTRACT
Normal glucose metabolism is critical to immune function but the effects of short-term hyperglycemia on immunity are not well described. To study this phenomenon, we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose and octreotide. An RNA-seq analysis of whole blood RNA demonstrated alterations in multiple immune pathways and transcripts during acute hyperglycemia including decreased transcription of IL-6, an important component of both innate and adaptive immune responses. Additional in vitro studies of human peripheral blood mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL-6 expression, most prominently in CD14(+)CD16(+) intermediate monocytes. Hyperglycemia also reduced IL-17A expression suggesting further impairment of immune responses during acute hyperglycemia. These findings demonstrate multiple defective immune responses in acute hyperglycemia and suggest a novel role for intermediate monocytes as metabolically sensitive innate immune cells.
