Myocardial Injury in Severe COVID-19 Compared With Non-COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Knowledge gaps remain in the epidemiology and clinical implications of myocardial injury in coronavirus disease 2019 (COVID-19). We aimed to determine the prevalence and outcomes of myocardial injury in severe COVID-19 compared with acute respiratory distress syndrome (ARDS) unrelated to COVID-19. METHODS: We included intubated patients with COVID-19 from 5 hospitals between March 15 and June 11, 2020, with troponin levels assessed. We compared them with patients from a cohort study of myocardial injury in ARDS and performed survival analysis with primary outcome of in-hospital death associated with myocardial injury. In addition, we performed linear regression to identify clinical factors associated with myocardial injury in COVID-19. RESULTS: Of 243 intubated patients with COVID-19, 51% had troponin levels above the upper limit of normal. Chronic kidney disease, lactate, ferritin, and fibrinogen were associated with myocardial injury. Mortality was 22.7% among patients with COVID-19 with troponin under the upper limit of normal and 61.5% for those with troponin levels >10 times the upper limit of normal (P<0.001). The association of myocardial injury with mortality was not statistically significant after adjusting for age, sex, and multisystem organ dysfunction. Compared with patients with ARDS without COVID-19, patients with COVID-19 were older and had higher creatinine levels and less favorable vital signs. After adjustment, COVID-19-related ARDS was associated with lower odds of myocardial injury compared with non-COVID-19-related ARDS (odds ratio, 0.55 [95% CI, 0.36-0.84]; P=0.005). CONCLUSIONS: Myocardial injury in severe COVID-19 is a function of baseline comorbidities, advanced age, and multisystem organ dysfunction, similar to traditional ARDS. The adverse prognosis of myocardial injury in COVID-19 relates largely to multisystem organ involvement and critical illness.

The Effectiveness of High-Flow Nasal Cannula in Coronavirus Disease 2019 Pneumonia: A Retrospective Cohort Study.

OBJECTIVES: High-flow nasal cannula is widely used in acute hypoxemic respiratory failure due to coronavirus disease 2019, yet data regarding its effectiveness is lacking. More evidence is needed to guide patient selection, timing of high-flow nasal cannula initiation, and resource allocation. We aimed to assess time to discharge and time to death in severe coronavirus disease 2019 in patients treated with high-flow nasal cannula compared with matched controls. We also evaluated the ability of the respiratory rate-oxygenation ratio to predict progression to invasive mechanical ventilation. DESIGN: Time-dependent propensity score matching was used to create pairs of individuals who were then analyzed in a Cox proportional-hazards regression model to estimate high-flow nasal cannula's effect on time to discharge and time to death. A secondary analysis excluded high-flow nasal cannula patients intubated within 6 hours of admission. A Cox proportional-hazards regression model was used to assess risk of invasive mechanical ventilation among high-flow nasal cannula patients stratified by respiratory rate-oxygenation. SETTING: The five hospitals of the Johns Hopkins Health System. PATIENTS: All patients who were admitted with a laboratory-confirmed diagnosis of coronavirus disease 2019 were eligible for inclusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-flow nasal cannula was associated with longer median time to discharge: 10.6 days (interquartile range, 7.1-15.8 d) versus 7.8 days (interquartile range, 4.9-12.1 d). Respiratory rate-oxygenation index performed poorly in predicting ventilation or death. In the primary analysis, there was no significant association between high-flow nasal cannula and hazard of death (adjusted hazard ratio, 0.79; 95% CI, 0.57-1.09). Excluding patients intubated within 6 hours of admission, high-flow nasal cannula was associated with reduced hazard of death (adjusted hazard ratio, 0.67; 95% CI, 0.45-0.99). CONCLUSIONS: Among unselected patients with severe coronavirus disease 2019 pneumonia, high-flow nasal cannula was not associated with a statistically significant reduction in hazard of death. However, in patients not mechanically ventilated within 6 hours of admission, high-flow nasal cannula was associated with a significantly reduced hazard of death.

Decoding Altered Consciousness: An Artery of Percheron Stroke.

The artery of Percheron (AOP) is a unique variant of the thalamic and midbrain perforating arteries. It originates from the P1 branch of the posterior cerebral artery (PCA) and supplies the bilateral paramedian thalami (BPT) along with variable contributions to the rostral midbrain. Four infarction patterns have been identified as a result of an AOP stroke, each associated with varying prognostic outcomes. We present an 89-year-old female with an AOP infarction and discuss the associated symptoms, implicated anatomy, and prognosis.

Outcomes Among Mechanically Ventilated Patients With Severe Pneumonia and Acute Hypoxemic Respiratory Failure From SARS-CoV-2 and Other Etiologies.

Importance: Early observations suggested that COVID-19 pneumonia had a higher mortality rate than other causes of pneumonia. Objective: To compare outcomes between mechanically ventilated patients with pneumonia due to COVID-19 (March 2020 to June 2021) and other etiologies (July 2016 to December 2019). Design, Setting, and Participants: This retrospective cohort study was conducted at the Johns Hopkins Healthcare System among adult patients (aged ≥18 years) with pneumonia who required mechanical ventilation in the first 2 weeks of hospitalization. Clinical, laboratory, and mechanical ventilation data were extracted from admission to hospital discharge or death. Exposures: Pneumonia due to COVID-19. Main Outcomes and Measures: The primary outcome was 90-day in-hospital mortality. Secondary outcomes were time to liberation from mechanical ventilation, hospital length of stay, static respiratory system compliance, and ventilatory ratio. Unadjusted and multivariable-adjusted logistic regression, proportional hazards regression, and doubly robust regression were used in propensity score-matched sets to compare clinical outcomes. Results: Overall, 719 patients (mean [SD] age, 61.8 [15.3] years; 442 [61.5%] were male; 460 [64.0%] belonged to a minoritized racial group and 253 [35.2%] were White) with severe COVID-19 pneumonia and 1127 patients (mean [SD] age, 60.9 [15.8] years; 586 [52.0%] were male; 459 [40.7%] belonged to a minoritized racial group and 655 [58.1%] were White) with severe non-COVID-19 pneumonia. In unadjusted analyses, patients with COVID-19 pneumonia had higher 90-day mortality (odds ratio, 1.21, 95% CI 1.04-1.41), longer time on mechanical ventilation (subdistribution hazard ratio 0.72, 95% CI 0.63-0.81), and lower compliance (32.0 vs 28.4 mL/kg PBW/cm H2O; P < .001) when compared with those with non-COVID-19 pneumonia. In propensity score-matched analyses, patients with COVID-19 pneumonia were equally likely to die within 90 days as those with non-COVID-19 pneumonia (odds ratio, 1.04; 95% CI, 0.81 to 1.35; P = .85), had similar respiratory system compliance (mean difference, 1.82 mL/cm H2O; 95% CI, -1.53 to 5.17 mL/cm H2O; P = .28) and ventilatory ratio (mean difference, -0.05; 95% CI, -0.22 to 0.11; P = .52), but had lower rates of liberation from mechanical ventilation (subdistribution hazard ratio, 0.81; 95% CI, 0.65 to 1.00) when compared with those with non-COVID-19 pneumonia. Patients with COVID-19 pneumonia had somewhat lower rates of being discharged from the hospital alive at 90 days (subdistribution hazard ratio, 0.83; 95% CI, 0.68 to 1.01) than those with non-COVID-19 pneumonia; however, this was not statistically significant. Conclusions and Relevance: In this study, mechanically ventilated patients with severe COVID-19 pneumonia had similar mortality rates as patients with other causes of severe pneumonia but longer times to liberation from mechanical ventilation. Mechanical ventilation use in COVID-19 pneumonia should follow the same evidence-based guidelines as for any pneumonia.

Palliative care in lung transplantation.

The role of palliative care in lung transplantation has grown exponentially in the past two decades. From assisting with evaluating and optimizing candidates for transplant, to playing a crucial role in patients requiring extracorporeal cardiopulmonary life support (ECLS) as a bridge to lung transplant, perioperatively, or even during their first year post-transplant, palliative care has been shown to be an effective if underutilized tool in the armamentarium used to care for lung transplant patients. For patients being considered for primary transplantation and for lung transplant recipients, palliative care can decrease symptom burden and help to lessen the psychological distress experienced by patients and family members. For older patients listed for transplant, palliative care can help address cognitive impairment, depression, and frailty. Patients listed for lung re-transplant also benefit from palliative care involvement to address frequent symptom exacerbations, hospitalizations, and higher morbidity and mortality. Even for organ donors and their families, palliative care can facilitate communication and provide support to the family. While palliative care use in lung transplantation may be gradually increasing, further work is necessary to optimally integrate palliative care into lung transplantation. Barriers to lung transplant patients receiving palliative care are multifactorial and include physician, patient, and institutional factors. The potential role of palliative care in every aspect of lung transplantation has made a knowledge of palliative care principles crucial for the lung transplant practitioner. In this review, we will clearly delineate the potential benefit of palliative care for the perioperative lung transplant patient and make an argument for its increased use in this patient population.

Comparing Prone Positioning Use in COVID-19 Versus Historic Acute Respiratory Distress Syndrome.

Use of prone positioning in patients with acute respiratory distress syndrome (ARDS) from COVID-19 may be greater than in patients treated for ARDS before the pandemic. However, the magnitude of this increase, sources of practice variation, and the extent to which use adheres to guidelines is unknown. OBJECTIVES: To compare prone positioning practices in patients with COVID-19 ARDS versus ARDS treated before the pandemic. DESIGN SETTING AND PARTICIPANTS: We conducted a multicenter retrospective cohort study of mechanically ventilated patients with early moderate-to-severe ARDS from COVID-19 (2020-2021) or ARDS from non-COVID-19 pneumonia (2018-2019) across 19 ICUs at five hospitals in Maryland. MAIN OUTCOMES AND MEASURES: The primary outcome was initiation of prolonged prone positioning (≥ 16 hr) within 48 hours of meeting oxygenation criteria. Comparisons were made between cohorts and within subgroups including academic versus community hospitals, and medical versus nonmedical ICUs. Other outcomes of interest included time to proning initiation, duration of prone sessions and temporal trends in proning frequency. RESULTS: Proning was initiated within 48 hours in 227 of 389 patients (58.4%) with COVID-19 and 11 of 123 patients (8.9%) with historic ARDS (49.4% absolute increase [95% CI for % increase, 41.7-57.1%]). Comparing COVID-19 to historic ARDS, increases in proning were similar in academic and community settings but were larger in medical versus nonmedical ICUs. Proning was initiated earlier in COVID-19 versus historic ARDS (median hours (hr) from oxygenation criteria, 12.9 vs 30.6; p = 0.002) and proning sessions were longer (median hr, 43.0 vs 28.0; p = 0.01). Proning frequency increased rapidly at the beginning of the pandemic and was sustained. CONCLUSIONS AND RELEVANCE: We observed greater overall use of prone positioning, along with shorter time to initiation and longer proning sessions in ARDS from COVID-19 versus historic ARDS. This rapid practice change can serve as a model for implementing evidence-based practices in critical care.

The effect of the cystic fibrosis care center on outcomes after lung transplantation for cystic fibrosis.

BACKGROUND: The purpose of this study was to evaluate outcomes in people with cystic fibrosis (CF) who underwent lung transplant (LT) at a transplant center with an accredited Cystic Fibrosis Care Center (CFCC) in the United States. METHODS: We reviewed the Scientific Registry of Transplant Recipients for all adult patients with CF who received a first-time LT from 2005 to 2018. The primary outcome was graft failure. Unadjusted Kaplan-Meier analysis and adjusted multilevel Cox proportional hazards models were used to evaluate outcomes in CF patients undergoing lung transplantation at a CFCC. RESULTS: 2,573 patients with CF underwent a first time LT during the study period. Of the 68 lung transplantation centers, 50 were CFCCs (73.5%). After adjustment for potential confounders, patients who underwent lung transplantation at a hospital with an accredited CFCC had a 33% reduction in risk of death or re-transplantation compared to those transplanted at a hospital without an accredited CFCC (HR: 0.67, 95% CI: 0.56-0.82, p < 0.001). CONCLUSIONS: People with CF who undergo LT at a transplant center with a CFCC have improved graft survival and decreased need for re-transplantation compared to those who undergo LT at a non-CFCC, independent of volume.

Top Ten Tips Palliative Care Clinicians Should Know About Solid Organ Transplantation.

Solid organ transplantation (SOT) is a life-saving procedure for people with end-stage organ failure. However, patients experience significant symptom burden, complex decision making, morbidity, and mortality during both pre- and post-transplant periods. Palliative care (PC) is well suited and historically underdelivered for the transplant population. This article, written by a team of transplant specialists (surgeons, cardiologists, nephrologists, hepatologists, and pulmonologists), PC clinicians, and an ethics specialist, shares 10 high-yield tips for PC clinicians to consider when caring for SOT patients.

The role of palliative care in lung transplantation.

Lung transplantation confers meaningful benefit for patients by extending life and improving quality of life. Palliative care is a medical specialty that likewise aims to improve the quality of life of patients enduring serious illness and their caregivers. Yet, while transplant candidates and recipients face serious illness they rarely receive palliative care, even at end of life. While limited palliative care utilization is likely multifactorial, one key reason is a limited understanding of the specialty of palliative care and evidence for palliative interventions. In this review, we address this key barrier by discussing in depth what the specialty of palliative care is and provides to patients and their caregivers. We then discuss the growing evidence for palliative care interventions to improve quality of life and reduce symptom burdens in patients with malignancy including those undergoing bone marrow transplantation and patients with chronic organ failure. We then consider what palliative care needs exist across pre and post transplantation based on studies of palliative care needs of patients with end stage lung disease, studies of quality of life after lung transplantation, and limited studies of palliative care utilization pre and post lung transplantation. Finally, we consider different models of palliative care and discuss how palliative care might optimally be incorporated in lung transplantation using a longitudinal, integrated approach to palliative care.

Donor-specific antibody characteristics, including persistence and complement-binding capacity, increase risk for chronic lung allograft dysfunction.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the major complication limiting long-term survival in lung transplant recipients (LTRs), with those developing donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) previously found to have increased risk for CLAD. However, as DSA responses vary in timing of development, specificity, breadth, persistence, and complement-binding capacity, we hypothesized that these characteristics would impact CLAD and survival outcomes. METHODS: We retrospectively analyzed DSA characteristics and outcomes in a single-center cohort of 582 LTRs who had serum samples collected prospectively from 2010 to 2016. Luminex-based single antigen bead assays were performed to assess DSA. RESULTS: DSAs were detected in 247 LTRs (42%), of which 124 (21.3%) were de novo DSAs and 53 (9.1%) were complement-binding (C1q+). CLAD developed in 208 LTRs (35.7%) during the follow-up period, with 67.8% determined as bronchiolitis obliterans syndrome phenotype and 32.2% as restrictive allograft syndrome phenotype. We found a shorter time to CLAD in LTRs with persistent DSAs (p = 0.04) and HLA-DQ-specific DSAs (p = 0.03). LTRs who developed C1q+ DSAs had significantly shorter time to CLAD (p < 0.001), with 100% of C1q+ DSAs being persistent and no differences between CLAD phenotypes. CLAD-free survival was significantly reduced in LTRs who developed C1q+ DSAs (p = 0.001), HLA-DQ-specific DSAs (p = 0.03), and multiple DSAs (p = 0.02). CONCLUSIONS: Together, our findings demonstrate that DSA characteristics of persistence, HLA-DQ specificity, and C1q+ DSAs are associated with shorter time to CLAD. Additionally, C1q+, HLA-DQ-specific, and multiple DSAs are associated with decreased CLAD-free survival. These characteristics may improve DSA risk stratification for deleterious outcomes in LTRs.

Lung Transplant Pulmonologists' Views of Specialty Palliative Care for Lung Transplant Recipients.

Background: Lung transplant recipients with serious illness may benefit from but rarely receive specialty palliative care (SPC) services. Transplant pulmonologists' views of SPC may be key to understanding SPC utilization but have not been well characterized. Objectives: (1) To understand how transplant pulmonologists view SPC and decide to refer transplant recipients and (2) to identify unique aspects of lung transplantation that may influence referral decisions. Design: We conducted semistructured interviews with transplant pulmonologists at nine geographically diverse high-volume North American transplant centers with SPC services. A multidisciplinary team analyzed interview transcripts using constant comparative methods to inductively develop and refine a coding framework related to SPC views and referral decisions. Results: We interviewed 38 transplant pulmonologists; most (36/38) had referred lung transplant recipients to SPC. Participants described SPC as a medical specialty that aims to improve quality of life and distinguished SPC from hospice care, which was considered end-of-life care. Participants who viewed transplant as a temporary solution (n = 17/38, 45%) described earlier utilization of SPC alongside disease-directed therapies, whereas those who viewed transplant as survival-focused (n = 21/38, 55%) described utilization of SPC after disease-directed therapies were exhausted. Concerns about one-year survival metrics and use of addicting medications for symptom palliation were barriers to referral. Conclusions: Transplant pulmonologists' SPC referral practices may be related to their views of lung transplantation. Optimizing use of SPC in lung transplantation will require improving communication between transplant pulmonology and SPC to ensure a collaborative effort toward patient-centered goals while addressing unique barriers to SPC referral.

Characteristics, Trends, and Predictors of Specialty Palliative Care Utilization after Lung Transplantation.

Background: Lung transplant recipients who experience serious illness could benefit from specialty palliative care (SPC), but evidence suggests that referral has been rare. Objective: Examine the characteristics of post-transplant SPC encounters, utilization trends, and patient characteristics associated with SPC at a center with established SPC services. Design: Retrospective cohort study of SPC utilization by 597 lung transplant recipients transplanted between 2010 and 2015. We collected data on pretransplant demographics and post-transplant SPC encounters, including timing, location, and referral reasons. Cumulative incidence of SPC and patient characteristics associated with SPC were examined by competing risks methods. Utilization in the first two post-transplant years was compared between subcohorts defined by year of transplantation. Results: SPC cumulative incidence was 27% and 43% at one and five years. More than 60% of encounters occurred in the first post-transplant year including 34% during the index transplant hospitalization. Over 90% of encounters occurred in the inpatient setting. The majority of consults were for symptom management. From 2010 to 2015 inpatient utilization in the first two post-transplant years increased from 23% to 42%, and outpatient utilization increased from 2% to 16%. Accounting for increasing utilization, pretransplant SPC and double-lung transplantation were associated with greater incidence of post-transplant SPC. Conclusions: Lung transplant recipients may have palliative care needs early after transplantation. Increasing utilization suggests greater awareness of or changing attitudes about the utility of SPC for lung transplant recipients. Understanding transplant recipients' palliative care needs and transplant physicians' views of SPC is critical to improving the provision of SPC in lung transplantation.

Adolescent exposure to nicotine impairs adult serial pattern learning in rats.

In the present study investigating the effects of adolescent nicotine exposure on adult serial pattern learning, adolescent rats received daily i.p. injections of either 1.0 mg/kg nicotine or saline for 5 days per week for 5 weeks beginning on postnatal day 25 (P25), then were allowed 35 days drug free. Rats then began training on P95 as adults on a 24-element serial pattern composed of eight 3-element chunks. Adolescent exposure to 1.0 mg/kg nicotine produced persistent retardation of learning for the first element of each 3-element chunk of the pattern, that is, for chunk boundary elements, and transient retardation of learning for elements 2 and 3 of each chunk of the pattern, that is, for the within-chunk elements. Deficits at chunk boundaries were interpreted as deficits of phrasing cue discrimination learning whereas deficits for learning responses for elements within-chunks (elements 2 and 3 of chunks) were interpreted as deficits of rule learning. These results indicate that the effects of adolescent nicotine exposure on adult learning and cognitive capacity deserve further scrutiny.

Adolescent reward system perseveration due to nicotine: studies with methylphenidate.

Previous data suggests adolescent nicotine exposure permanently disrupts reward systems. Behavioral pharmacological methods were used to assess the effects of adolescent nicotine exposure on methylphenidate (MPD) sensitivity and reward from adolescence to adulthood. For experiment one, testing was performed on adult mice exposed to nicotine (0.3 and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (PND 25-57). After a 28-day drug-free, time-off period, the locomotor effects (30 min, 30 cm traveled) of MPD (5, 10, 20, and 40 mg/kg, IP) were measured. Thereafter, mice underwent condition-place-preference testing (CPP). MPD (20 mg/kg) was paired with the subject's non-preferred side and saline with the preferred side. Conditioning sessions were conducted for 8 days with a drug-free post-test on the day following the final conditioning session. A second experiment was conducted to determine if adolescent mice respond differently to MPD compared to adult mice. The study compared adolescent mice (PND 25-46) to adult mice (PND 77-98) using identical MPD testing procedures as in experiment one. Adult subjects exposed to nicotine during adolescence behaved remarkably similar to adolescent subjects receiving only MPD. Both nicotine exposed subjects and naïve adolescents exhibited increased response to MPD's motor activating effects and a decreased response to MPD's rewarding effects. Taken together it appears that adolescent nicotine exposure retards the development of reward systems, thus, maintaining an adolescent state indefinitely, which could result in increased vulnerability to substance abuse problems throughout adulthood.

A targeted educational intervention to reduce ventilator-associated complications.

The optimal approach for the prevention of ventilator-associated complications (VACs) is currently unknown. A retrospective pre-post intervention analysis was conducted to assess a multifaceted educational intervention targeting the most common causes for VACs and VAC risk factors. Results indicated that the addition of this intervention to existing infection control and treatment protocols did not demonstrate a decrease in VAC occurrence or duration of mechanical ventilation.

Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus.

Traumatic CNS injury activates and mobilizes resident parenchymal microglia (MG), which rapidly accumulate near injured neurons where they transform into phagocytes. The mechanisms underlying this rapid 'homing' in situ are unknown. Using time-lapse confocal imaging in acutely excised neonatal hippocampal slices, we show that rapid accumulation of MG near somata of injured pyramidal neurons in the stratum pyramidale (SP) results from directed migration from tissue regions immediately adjacent to (<200 microm from) the SP. Time-lapse sequences also reveal a 'spreading activation wave' wherein MG situated progressively farther from the SP begin to migrate later and exhibit less directional migration toward the SP. Because purines have been implicated in MG activation and chemotaxis, we tested whether ATP/ADP released from injured pyramidal neurons might account for these patterns of MG behavior. Indeed, application of apyrase, which degrades extracellular ATP/ADP, inhibits MG motility and homing to injured neurons in the SP. Moreover, bath application of exogenous ATP/ADP disrupts MG homing by inducing directional migration toward the slice exterior and away from injured neurons. These results indicate that extracellular ATP/ADP is both necessary and sufficient to induce directional migration and rapid homing of neonatal MG to injured neurons in situ. Rapid, ATP/ADP-dependent MG homing may promote clearance of dead and dying cells and help limit secondary damage during the critical first few hours after neuronal injury.