Effect of the UNOS policy change on rates of rejection, infection and hospital readmission following heart transplantation.

BACKGROUND: The 2018 adult heart allocation policy sought to improve waitlist risk stratification, reduce waitlist mortality and increase organ access. This system prioritized patients at greatest risk for waitlist mortality, especially individuals requiring temporary mechanical circulatory support (tMCS). Post-transplant complications are significantly higher in patients on tMCS before transplantation, and early post-transplant complications impact long-term mortality. We sought to determine if policy change affected early post-transplant complication rates of rejection, infection and hospitalization. METHODS: We included all adult, heart-only, single-organ heart transplant recipients from the UNOS registry with pre-policy (PRE) individuals transplanted between 11/1/2016 to 10/31/2017 and post-policy (POST) between 11/1/2018 to 10/31/2019. We used a multivariable logistic regression analysis to assess the effect of policy change on post-transplant rejection, infection, and hospitalization. Two COVID-19 eras (2019-2020, 2020-2021) were included in our analysis. RESULTS: The majority of baseline characteristics were comparable between PRE and POST era recipients. The odds of treated rejection (p=0.8), hospitalization (p=0.69), and hospitalization due to rejection (p=0.76) and infection (p=0.66) were similar between PRE and POST eras; there was a trend towards reduced odds of rejection (p=0.08). In both COVID eras, there was a clear reduction in rejection and treated rejection with no effect on hospitalization for rejection or infection. Odds of all-cause hospitalization was increased in both COVID eras. CONCLUSION: The UNOS policy change improves access to heart transplantation for higher acuity patients without increasing early post-transplant rates of treated rejection or hospitalization for rejection or infection, factors which portend risk for long-term post-transplant mortality.

Variation in survival in patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation: A multi-institutional analysis of 594 consecutive patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation at 49 hospitals within 21 states.

OBJECTIVES: We reviewed 594 consecutive patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation at 49 hospitals within 21 states and examined patient characteristics, treatments, and variation in outcomes over the course of the pandemic. METHODS: A multi-institutional database was used to assess all patients with Coronavirus Disease 2019 supported with and separated from extracorporeal membrane oxygenation between March 2020 and December 2021, inclusive. Descriptive analysis was stratified by 4 time categories: group A = March 2020 to June 2020, group B = July 2020 to December 2020, group C = January 2021 to June 2021, group D = July 2021 to December 2021. A Bayesian mixed-effects logistic regression was used to assess continuous trends in survival where time was operationalized as the number of days between each patient's cannulation and that of the first patient in March 2020, controlling for multiple variables and risk factors. RESULTS: At hospital discharge, of 594 patients, 221 survived (37.2%) and 373 died. Throughout the study, median age [interquartile range] declined (group A = 51.0 [41.0-60.0] years, group D = 39.0 [32.0-48.0] years, P < .001); median days between Coronavirus Disease 2019 diagnosis and intubation increased (group A = 4.0 [1.0-8.5], group D = 9.0 [5.0-14.5], P < .001); and use of medications (glucocorticoids, interleukin-6 blockers, antivirals, antimalarials) and convalescent plasma fluctuated significantly (all P < .05). Estimated odds of survival varied over the study period with a decline between April 1, 2020, and November 21, 2020 (odds ratio, 0.39, 95% credible interval, 0.18-0.87, probability of reduction in survival = 95.7%), improvement between November 21, 2020, and May 17, 2021 (odds ratio, 1.85, 95% credible interval, 0.86-4.09, probability of improvement = 93.4%), and decline between May 17, 2021, and December 1, 2021 (odds ratio, 0.49, 95% credible interval, 0.19-1.44, probability of decrease = 92.1%). CONCLUSIONS: Survival for patients with Coronavirus Disease 2019 supported with extracorporeal membrane oxygenation has fluctuated during the stages of the pandemic. Minimizing variability by adherence to best practices may refine the optimal use of extracorporeal membrane oxygenation in a pandemic response.

Clinical Course of Two Patients with COVID-19 Respiratory Failure After Administration of the Anticancer Small Molecule, RRx-001.

Two critically ill COVID-19 infected patients, who had exhausted all available treatment options, were treated with the small-molecule RRx-001 with subsequent improvement. RRx-001, a first-in-class small molecule with anti-inflammatory, vascular normalizing and macrophage-repolarizing properties, has been safely administered 300+ patients in clinical trials. This is the first report of RRx-001 treatment of COVID-19.

Affectivity, subjectivity, and vulnerability: on the new forces of mass hysteria

Affect theory raises greater awareness of non-representational forces in social life that can shape different levels of subjectivity in ways that may not be immediately known to the subjects. In outbreaks of mass hysteria when subjects are suddenly exposed to bizarre and extreme behaviors, the question of affect becomes a key to understanding how their subjectivity is impacted by situations that seemingly slip immediate control. Hysterical subjectivity occurs not from unconscious forces but from affective contagions spreading throughout network assemblages. These are flows of fear and conflict that with non-conscious influences constitute the new forces of mass encounters. In these encounters, micro-flows of imitation are automatized by various assemblages of intention and action to produce repeatable contagions of affects and behaviors. The occurrence of the COVID-19 pandemic demonstrates the power of these flows as facilitating a global affectivity of mass hysteria. It is an affectivity in which imitation takes on a central role as technology of the social for the behavioral control of mass populations. Ubiquitous mask-wearing in the pandemic is not only seen as a prophylactic against viral infection but also intended as a mandated form of mimicry for propagating the new politics of virality. These are politics that empower fear as an agent of cascading contagions paralyzing social, cultural, and economic life around the world.

Citizen science reveals unexpected solute patterns in semiarid river networks.

Human modification of water and nutrient flows has resulted in widespread degradation of aquatic ecosystems. The resulting global water crisis causes millions of deaths and trillions of USD in economic damages annually. Semiarid regions have been disproportionately affected because of high relative water demand and pollution. Many proven water management strategies are not fully implemented, partially because of a lack of public engagement with freshwater ecosystems. In this context, we organized a large citizen science initiative to quantify nutrient status and cultivate connection in the semiarid watershed of Utah Lake (USA). Working with community members, we collected samples from ~200 locations throughout the 7,640 km2 watershed on a single day in the spring, summer, and fall of 2018. We calculated ecohydrological metrics for nutrients, major ions, and carbon. For most solutes, concentration and leverage (influence on flux) were highest in lowland reaches draining directly to the lake, coincident with urban and agricultural sources. Solute sources were relatively persistent through time for most parameters despite substantial hydrological variation. Carbon, nitrogen, and phosphorus species showed critical source area behavior, with 10-17% of the sites accounting for most of the flux. Unlike temperate watersheds, where spatial variability often decreases with watershed size, longitudinal variability showed an hourglass shape: high variability among headwaters, low variability in mid-order reaches, and high variability in tailwaters. This unexpected pattern was attributable to the distribution of human activity and hydrological complexity associated with return flows, losing river reaches, and diversions in the tailwaters. We conclude that participatory science has great potential to reveal ecohydrological patterns and rehabilitate individual and community relationships with local ecosystems. In this way, such projects represent an opportunity to both understand and improve water quality in diverse socioecological contexts.

Acute disseminated encephalomyelitis with bilateral optic neuritis following ChAdOx1 COVID-19 vaccination.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory demyelinating disease of the central nervous system. We report a case of ADEM presenting with bilateral optic neuritis temporally associated with the ChAdOx1 vaccine against SARS-COVID19 virus. CASE PRESENTATION: A 36-year-old female presented with bilateral optic neuritis following her first dose of the ChAdOx1 vaccine. Initial MRI Brain showed evidence of demyelination within the subcortical white matter, with no radiological involvement of the optic nerves. Visual evoked potentials were consistent with bilateral optic neuritis which was confirmed radiologically on follow up MRI. She was treated with intravenous steroids with improvement both in symptoms and radiological appearance. A pseudo-relapse occurred which was treated with a further course of intravenous steroids followed by an oral taper. The clinical, radiological and serological results were most consistent with diagnosis of ADEM. CONCLUSIONS: ADEM is an exceedingly rare complication of ChAdOx1 vaccine despite millions of doses. While it is imperative clinicians remain aware of neurological complications of vaccines, the importance of vaccination to control a pandemic should not be undermined.

Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by respiratory distress, multiorgan dysfunction, and, in some cases, death. The pathological mechanisms underlying COVID-19 respiratory distress and the interplay with aggravating risk factors have not been fully defined. Lung autopsy samples from 18 patients with fatal COVID-19, with symptom onset-to-death times ranging from 3 to 47 days, and antemortem plasma samples from 6 of these cases were evaluated using deep sequencing of SARS-CoV-2 RNA, multiplex plasma protein measurements, and pulmonary gene expression and imaging analyses. Prominent histopathological features in this case series included progressive diffuse alveolar damage with excessive thrombosis and late-onset pulmonary tissue and vascular remodeling. Acute damage at the alveolar-capillary barrier was characterized by the loss of surfactant protein expression with injury to alveolar epithelial cells, endothelial cells, respiratory epithelial basal cells, and defective tissue repair processes. Other key findings included impaired clot fibrinolysis with increased concentrations of plasma and lung plasminogen activator inhibitor-1 and modulation of cellular senescence markers, including p21 and sirtuin-1, in both lung epithelial and endothelial cells. Together, these findings further define the molecular pathological features underlying the pulmonary response to SARS-CoV-2 infection and provide important insights into signaling pathways that may be amenable to therapeutic intervention.

Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study.

BACKGROUND: Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. OBJECTIVE: The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. METHODS: This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. RESULTS: There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. CONCLUSION AND RELEVANCE: Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.