Early pandemic in-hospital outcomes and mortality risk factors in COVID-19 solid organ transplant patients.

Background: Solid organ transplant (SOT) recipients with COVID-19 have a higher risk of mortality than those without COVID-19. However, it is unclear how SOT patient outcomes compare to the general population without SOT who contract COVID-19. Methods: We used the National Inpatient Sample from January to December 2020 to investigate inpatient outcomes seen in SOT recipients after contracting COVID-19 compared to nontransplant patients. We identified our study sample using ICD-10 CM and excluded those <18 years of age and those with dual organ transplants. Inpatient outcomes were compared in SOT and non-SOT COVID cohorts, and we further evaluated predictors of mortality in the SOT with COVID population. Results: Out of the 1,416,445 COVID-19 admissions included in the study, 8315 (0.59%) were single SOT recipients. Our analysis that adjusted for multiple baseline characteristics and comorbidities demonstrated that COVID-19 in SOT patients was associated with higher rates of acute kidney injury (adjusted odds ratio [aOR] 2.34, 95% confidence interval [CI] 1.81-3.02, P < 0.01), lower rates of acute respiratory distress syndrome (aOR 0.68, 95% CI 0.54-0.85, P < 0.01), and similar rates of cardiac arrest, pulmonary embolism, circulatory shock, cerebrovascular events, and in-hospital mortality. Age >65 was associated with mortality in SOT patients. Conclusion: In this nationally representative sample, SOT patients presenting with COVID-19 experienced similar rates of mortality compared to those without SOT. SOT patients were more likely to develop acute kidney injury. Further research is needed to understand the complex relationship between transplant patient outcomes and COVID-19.

Discrete-state models identify pathway specific B cell states across diseases and infections at single-cell resolution.

Oxygen (O2) regulated pathways modulate B cell activation, migration and proliferation during infection, vaccination, and other diseases. Modeling these pathways in health and disease is critical to understand B cell states and ways to mediate them. To characterize B cells by their activation of O2 regulated pathways we develop pathway specific discrete state models using previously published single-cell RNA-sequencing (scRNA-seq) datasets from isolated B cells. Specifically, Single Cell Boolean Omics Network Invariant-Time Analysis (scBONITA) was used to infer logic gates for known pathway topologies. The simplest inferred set of logic gates that maximized the number of "OR" interactions between genes was used to simulate B cell networks involved in oxygen sensing until they reached steady network states (attractors). By focusing on the attractors that best represented sequenced cells, we identified genes critical in determining pathway specific cellular states that corresponded to diseased and healthy B cell phenotypes. Specifically, we investigate the transendothelial migration, regulation of actin cytoskeleton, HIF1A, and Citrate Cycle pathways. Our analysis revealed attractors that resembled the state of B cell exhaustion in HIV+ patients as well as attractors that promoted anerobic metabolism, angiogenesis, and tumorigenesis in breast cancer patients, which were eliminated after neoadjuvant chemotherapy (NACT). Finally, we investigated the attractors to which the Azimuth-annotated B cells mapped and found that attractors resembling B cells from HIV+ patients encompassed a significantly larger number of atypical memory B cells than HIV- attractors. Meanwhile, attractors resembling B cells from breast cancer patients post NACT encompassed a reduced number of atypical memory B cells compared to pre-NACT attractors.

Paradoxical improvement of cognitive control in older adults under dual-task walking conditions is associated with more flexible reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study.

Combining walking with a demanding cognitive task is traditionally expected to elicit decrements in gait and/or cognitive task performance. However, it was recently shown that, in a cohort of young adults, most participants improved performance when walking was added to performance of a Go/NoGo response inhibition task. The present study aims to extend these previous findings to an older adult cohort, to investigate whether this improvement when dual-tasking is observed in healthy older adults. Mobile Brain/Body Imaging (MoBI) was used to record electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and behavioral responses in the Go/NoGo task, during sitting or walking on a treadmill, in 34 young adults and 37 older adults. Increased response accuracy during walking, independent of age, was found to correlate with slower responses to stimuli (r = 0.44) and with walking-related EEG amplitude modulations over frontocentral regions (r = 0.47) during the sensory gating (N1) and conflict monitoring (N2) stages of inhibition, and over left-lateralized prefrontal regions (r = 0.47) during the stage of inhibitory control implementation (P3). These neural activity changes are related to the cognitive component of inhibition, and they were interpreted as signatures of behavioral improvement during walking. On the other hand, aging, independent of response accuracy during walking, was found to correlate with slower treadmill walking speeds (r = -0.68) and attenuation in walking-related EEG amplitude modulations over left-dominant frontal (r = -0.44) and parietooccipital regions (r = 0.48) during the N2 stage, and over centroparietal regions (r = 0.48) during the P3 stage. These neural activity changes are related to the motor component of inhibition, and they were interpreted as signatures of aging. Older adults whose response accuracy 'paradoxically' improved during walking manifested neural signatures of both behavioral improvement and aging, suggesting that their flexibility in reallocating neural resources while walking might be maintained for the cognitive but not for the motor inhibitory component. These distinct neural signatures of aging and behavior can potentially be used to identify 'super-agers', or individuals at risk for cognitive decline due to aging or neurodegenerative disease.

Surgical and Device Interventions in the Treatment of Chronic Thromboembolic Disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by unresolved clot burden in large pulmonary arteries, obstructive disease in smaller arteries, and increased downstream clot burden. This occurs in the setting of abnormal fibrinolysis or hematological disorders. Up to 50% of patients in some studies are unaware of a self-history of a deep venous thrombosis or pulmonary embolism. Ultimately, they present with symptoms of pulmonary hypertension (PH), which can result in right heart failure (RHF). Pulmonary endarterectomy (PEA) is curative, though many patients have prohibitive surgical risk or surgically inaccessible disease, warranting other interventions such as balloon pulmonary angioplasty (BPA) and medical therapy. Rarely, other treatment options may be implemented. We focus this review on PEA and BPA, with an overview of the history of CTEPD and the evolution of these procedures. We will briefly discuss other treatment modalities.

Rapidly progressive pulmonary hypertension and right ventricular failure in a heart and kidney transplant recipient.

A 54-year-old man status post heart and kidney transplant presented with dyspnea. Imaging was consistent with lymphangitic carcinomatosis (LC), in the setting of biopsy proven adenocarcinoma. He developed pulmonary hypertension (PH) and died of right ventricular failure (RVF) 3 weeks later. Acute PH with radiographic features of LC in a high-risk patient warrants expedited malignancy investigation.

Vericiguat in Heart Failure with a Reduced Ejection Fraction: Patient Selection and Special Considerations.

With improvement in the understanding of the pathophysiological mechanisms of heart failure with reduced ejection fraction (HFrEF), several drug classes have been developed targeting the renin-angiotensin-aldosterone system, the beta adrenergic system, and to a certain extent the nitric oxide pathway. Recently, the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors has resulted in a reduction in heart failure hospitalizations and cardiovascular death. As a result, SGLT-2 inhibitors are now the fourth drug class recommended as part of guideline-directed medical therapy (GDMT) for HFrEF. Soluble guanylate cyclase (sGC) stimulators, such as vericiguat, are a novel therapy targeting the cyclic guanosine monophosphate (cGMP) pathway with downstream effects including smooth muscle cell relaxation and a reduction in hypertrophy, inflammation, and fibrosis. The recently published VICTORIA trial has demonstrated a reduction in heart failure hospitalizations or cardiovascular death with vericiguat. Patients with a baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) values <8000 pg/mL may identify a sub-group most likely to benefit with addition of vericiguat. The cumulative benefit of quadruple therapy with the addition of sGC stimulators remains unknown. We review the mechanism of action for sGC stimulators, clinical trial data, and their real-world application to HFrEF patients with consideration of quintuple therapy.

Transition from parenteral prostacyclins to selexipag: safety and feasibility in selected patients.

There are limited data regarding the feasibility of transitioning from intravenous prostacyclins to selexipag in pulmonary arterial hypertension patients. We present a case series of successful transitions from intravenous prostacyclins to selexipag in the majority of carefully selected five stable pulmonary arterial hypertension patients using a standardized protocol in the outpatient setting.

Inhalation of marijuana affects Drosophila heart function.

We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for studying human diseases. Adult flies were exposed to marijuana for variable time periods and the effects on cardiac function were studied. Short treatment protocol incremented heart-rate variability. Contractility was augmented only under prolonged exposure to cannabis and it was associated with incremented calcium transient within cardiomyocytes. Neither the activity of the major proteins responsible for calcium handling nor the calcium load of the sarcoplasmic reticulum were affected by the cannabis treatment. The observed changes manifested in the cardiomyocytes even in the absence of the canonical cannabinoid receptors described in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster. By providing a simple and affordable platform prior to mammalian models, this characterization of cardiac function under marijuana exposure opens new paths for conducting genetic screenings using vaporized compounds.This article has an associated First Person interview with the first author of the paper.