ECG and Atrial Appendage Doppler Discordance Is Common in Patients Undergoing Cardiac Surgery: Prospective Study.

Background: Patients with atrial fibrillation (AF) remain at increased risk of thromboembolism despite apparent maintenance of sinus rhythm with the cause often attributed to periods of asymptomatic AF. Atrial mechanical discordance, with the body of the left atrium (LA) in sinus rhythm and the left atrial appendage (LAA) in AF may also be a contributor.

Objectives: The purpose of this study was to assess the frequency of electrocardiogram (ECG) rhythm and LAA and/right atrial appendage (RAA) Doppler ejection phenotype (transesophageal echocardiography [TEE]) discordance in patients undergoing cardiac surgery.

Future pandemics and the urge to 'do something'.

Research with enhanced potential pandemic pathogens (ePPP) makes pathogens substantially more lethal, communicable, immunosuppressive or otherwise capable of triggering a pandemic. We briefly relay an existing argument that the benefits of ePPP research do not outweigh its risks and then consider why proponents of these arguments continue to confidently endorse them. We argue that these endorsements may well be the product of common cognitive biases-in which case they would provide no challenge to the argument against ePPP research.

A prospective, single-center, randomized phase 2 trial of etoposide in severe COVID-19.

The systemic inflammatory response seen in patients with severe COVID-19 shares many similarities with the changes observed in hemophagocytic lymphohistiocytosis (HLH); a disease characterized by excessive immune activation. Many patients with severe COVID qualify for a diagnosis of HLH. Etoposide, an inhibitor of topoisomerase II is used to control inflammation in HLH.

Philosophy instruction changes views on moral controversies by decreasing reliance on intuition.

What changes people's judgments on moral issues, such as the ethics of abortion or eating meat? On some views, moral judgments result from deliberation, such that reasons and reasoning should be primary drivers of moral change. On other views, moral judgments reflect intuition, with reasons offered as post-hoc rationalizations. We test predictions of these accounts by investigating whether exposure to a moral philosophy course (vs.

Primary intracranial extraosseous Ewing's sarcoma of the skull base in an elderly adult: illustrative case.

Background: Primary extraosseous intracranial Ewing's sarcoma, also known as a peripheral primitive neuroectodermal tumor or "small round blue cell tumor," is an extremely rare entity with limited representation in the literature beyond the pediatric population.

Observations: A 67-year-old male suffering occipital headache, nausea, and gait disturbance was found to have a large, avidly contrast-enhancing cerebellopontine angle mass extending into the cervical spinal canal with associated mass effect on medulla, cerebellum, fourth ventricle, and cervical spinal cord. This mass was not present on the imaging from 8 years prior.

Underrepresentation of Black participants and adverse events in clinical trials of lenalidomide for myeloma.

Adverse events affecting Black patients, including skin hyperpigmentation, may be overlooked using existing clinical trial data on lenalidomide. The objective of this systematic review is to characterize the representation of Black participants and rate of skin hyperpigmentation in clinical trials. In this systematic review and pooled analysis of 21 clinical trials comprising 4539 participants, the proportion of Black participants in trials (6.

New Uses for Thromboelastography and Other Forms of Viscoelastic Monitoring in the Emergency Department: A Narrative Review.

Patients frequently visit the emergency department with conditions that place them at risk of worse outcomes when accompanied by coagulopathy. Routine tests of coagulation-prothrombin time, partial thromboplastin time, platelets, and fibrinogen-have shortcomings that limit their use in providing emergency care. One alternative is to investigate coagulation disturbance with viscoelastic monitoring (VEM), a coagulation test that measures the timing and strength of blood clot development in real time.

SARS-CoV-2 Infection-Associated Hemophagocytic Lymphohistiocytosis.

Objectives: A subset of coronavirus disease 2019 (COVID-19) patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis (HLH) have not been reported. We studied the reticuloendothelial organs of 4 consecutive patients who died of COVID-19 and correlated with clinical and laboratory parameters to detect HLH.

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics.

Objective: Transcranial magnetic stimulation (TMS) can cause seizures in healthy individuals and patients. However, the rate at which this occurs is unknown. We estimated the risk of seizure and other adverse events with TMS.

De novo NAD biosynthetic impairment in acute kidney injury in humans.

Nicotinamide adenine dinucleotide (NAD) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD and mediates resistance to acute kidney injury (AKI).

Anaplastic large cell lymphoma localized to the left breast years after radiotherapy for breast cancer.

Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma that can involve the skin primarily or secondarily. Our case describes an unusual presentation of eruptive tumors localized to the leftbreast region several years following breast cancer surgery and radiation for carcinoma of the breast. This report highlights the challenges in reachingthe diagnosis of an aggressive systemic lymphoma presenting on the skin.

Identification and characterization of a potent and biologically-active PDE4/7 inhibitor via fission yeast-based assays.

We previously constructed a collection of fission yeast strains that express various mammalian cyclic nucleotide phosphodiesterases (PDEs) and developed a cell-based high throughput screen (HTS) for small molecule PDE inhibitors. Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells.

Responses to romidepsin in patients with cutaneous T-cell lymphoma and prior treatment with systemic chemotherapy.

Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy.

Clinical Efficacy of Romidepsin in Tumor Stage and Folliculotropic Mycosis Fungoides.

Background: Tumor stage and folliculotropic mycosis fungoides are uncommon subtypes of cutaneous T-cell lymphoma (CTCL) with an aggressive disease course. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with CTCL who have received ≥ 1 previous systemic therapy. In the present study, we examined the efficacy and safety of romidepsin in patients from the pivotal, single-arm, open-label, phase II study of relapsed or refractory CTCL with cutaneous tumors and/or folliculotropic disease involvement.

Anti-inflammatory effects of novel barbituric acid derivatives in T lymphocytes.

We have used a high throughput small molecule screen, using a fission yeast-based assay, to identify novel phosphodiesterase 7 (PDE7) inhibitors. One of the most effective hit compounds was BC12, a barbituric acid-based molecule that exhibits unusually potent immunosuppressive and immunomodulatory actions on T lymphocyte function, including inhibition of T cell proliferation and IL-2 cytokine production. BC12 treatment confers a >95% inhibition of IL-2 secretion in phytohaemagglutinin (PHA) plus phorbol-12-myristate-13-acetate (PMA) stimulated Jurkat T cells.

Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial.

Background: Thiamine is a vitamin that is essential for adequate aerobic metabolism. The objective of this study was to determine if thiamine administration prior to coronary artery bypass grafting would decrease post-operative lactate levels as a measure of increased aerobic metabolism.

Methods: We performed a randomized, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass grafting.

Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways.