Fibrotic-Like Pulmonary Radiographic Patterns Are Not Associated With Adverse Outcomes in COVID-19 Chronic Critical Illness.

OBJECTIVES: Pulmonary fibrosis is a feared complication of COVID-19. To characterize the risks and outcomes associated with fibrotic-like radiographic abnormalities in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and chronic critical illness. DESIGN: Single-center prospective cohort study. SETTING: We examined chest CT scans performed between ICU discharge and 30 days after hospital discharge using established methods to quantify nonfibrotic and fibrotic-like patterns. PATIENTS: Adults hospitalized with COVID-19-related ARDS and chronic critical illness (> 21 d of mechanical ventilation, tracheostomy, and survival to ICU discharge) between March 2020 and May 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested associations of fibrotic-like patterns with clinical characteristics and biomarkers, and with time to mechanical ventilator liberation and 6-month survival, controlling for demographics, comorbidities, and COVID-19 therapies. A total of 141 of 616 adults (23%) with COVID-19-related ARDS developed chronic critical illness, and 64 of 141 (46%) had a chest CT a median (interquartile range) 66 days (42-82 d) after intubation. Fifty-five percent had fibrotic-like patterns characterized by reticulations and/or traction bronchiectasis. In adjusted analyses, interleukin-6 level on the day of intubation was associated with fibrotic-like patterns (odds ratio, 4.40 per quartile change; 95% CI, 1.90-10.1 per quartile change). Other inflammatory biomarkers, Sequential Organ Failure Assessment score, age, tidal volume, driving pressure, and ventilator days were not. Fibrotic-like patterns were not associated with longer time to mechanical ventilator liberation or worse 6-month survival. CONCLUSIONS: Approximately half of adults with COVID-19-associated chronic critical illness have fibrotic-like patterns that are associated with higher interleukin-6 levels at intubation. Fibrotic-like patterns are not associated with longer time to liberation from mechanical ventilation or worse 6-month survival.

Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19.

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.

Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study.

BACKGROUND: Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. METHODS: This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation. FINDINGS: Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51-72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9-28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1-6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09-1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08-2·86]), chronic pulmonary disease (aHR 2·94 [1·48-5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02-1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01-1·19] per decile increase) were independently associated with in-hospital mortality. INTERPRETATION: Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality. FUNDING: National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.

Moral distress and burnout in caring for older adults during medical school training.

BACKGROUND: Moral distress is a reason for burnout in healthcare professionals, but the clinical settings in which moral distress is most often experienced by medical students, and whether moral distress is associated with burnout and career choices in medical students is unknown. We assessed moral distress in medical students while caring for older patients, and examined associations with burnout and interest in geriatrics. METHODS: A cross-sectional survey study of second-, third-, and fourth-year medical students at an American medical school. The survey described 12 potentially morally distressing clinical scenarios involving older adult patients. Students reported if they encountered each scenario, and whether they experienced moral distress, graded on a 1-10 scale. We conducted a principal axis factor analysis to assess the dimensionality of the survey scenarios. A composite moral distress score was calculated as the sum of moral distress scores across all 12 scenarios. Burnout was assessed using the Maslach Abbreviated Burnout Inventory, and interest in geriatrics was rated on a 7-point Likert scale. RESULTS: Two-hundred and nine students responded (47%), of whom 90% (188/209) reported moral distress in response to ≥1 scenario with a median (IQR) score of 6 (4-7). Factor analysis suggested a unidimensional factor structure of the 12 survey questions that reliably measured individual distress (Cronbach alpha = 0.78). Those in the highest tertile of composite moral distress scores were more likely to be burnt out (51%) than those in the middle tertile of scores (34%), or lowest tertile of scores (31%) (p = 0.02). There was a trend towards greater interest in geriatrics among those in the higher tertiles of composite moral distress scores (16% lowest tertile, 20% middle tertile, 25% highest tertile, p-for-tend = 0.21). Respondents suggested that moral distress might be mitigated with didactic sessions in inpatient geriatric care, and debriefing sessions with peers and faculty on the inpatient clerkships on medicine, neurology, and surgery, where students most often reported experiencing moral distress. CONCLUSIONS: Moral distress is highly prevalent among medical students while caring for older patients, and associated with burnout. Incorporating geriatrics education and debriefing sessions into inpatient clerkships could alleviate medical student moral distress and burnout.

Systemic thrombolysis in a patient with massive pulmonary embolism and recent glioblastoma multiforme resection.

While trials of systemic thrombolysis for submassive and massive pulmonary embolism (PE) report intracranial haemorrhage (ICH) rates of 2%-3%, the risk of ICH in patients with recent brain surgery or intracranial neoplasm is unknown since these patients were excluded from these trials. We report a case of massive PE treated with systemic thrombolysis in a patient with recent neurosurgery for an intracranial neoplasm. We discuss the risks and benefits of systemic thrombolysis for massive PE in the context of previous case reports, prior cohort studies and trials, and current guidelines. There may be times when the immediate risk of death from massive PE outweighs the risk of ICH from systemic thrombolysis, even when guideline-listed major contraindications exist. This case provides an example of how the haemodynamic benefit of systemic thrombolysis outweighed the impact of ICH in a patient who had undergone recent neurosurgical resection of a glioblastoma multiforme tumour.

Frailty and maximal exercise capacity in adult lung transplant candidates.

BACKGROUND: Frail lung transplant candidates are more likely to be delisted or die without receiving a transplant. Further knowledge of what frailty represents in this population will assist in developing interventions to prevent frailty from developing. We set out to determine whether frail lung transplant candidates have reduced exercise capacity independent of disease severity and diagnosis. METHODS: Sixty-eight adult lung transplant candidates underwent cardiopulmonary exercise testing (CPET) and a frailty assessment (Fried's Frailty Phenotype (FFP)). Primary outcomes were peak workload and peak aerobic capacity (V˙O2). We used linear regression to adjust for age, gender, diagnosis, and lung allocation score (LAS). RESULTS: The mean ± SD age was 57 ± 11 years, 51% were women, 57% had interstitial lung disease, 32% had chronic obstructive pulmonary disease, 11% had cystic fibrosis, and the mean LAS was 40.2 (range 19.2-94.5). In adjusted models, peak workload decreased by 10 W (95% CI 4.7 to 14.6) and peak V˙O2 decreased by 1.8 mL/kg/min (95% CI 0.6 to 2.9) per 1 unit increment in FFP score. After adjustment, exercise tolerance was 38 W lower (95% CI 18.4 to 58.1) and peak V˙O2 was 8.5 mL/kg/min lower (95% CI 3.3 to 13.7) among frail participants compared to non-frail participants. Frailty accounted for 16% of the variance (R2) of watts and 19% of the variance of V˙O2 in adjusted models. CONCLUSION: Frailty contributes to reduced exercise capacity among lung transplant candidates independent of disease severity.

The Frailty Phenotype and Palliative Care Needs of Older Survivors of Critical Illness.

OBJECTIVES: To assess symptoms in older intensive care unit (ICU) survivors and determine whether post-ICU frailty identifies those with the greatest palliative care needs. DESIGN: A prospective cohort study. SETTING: Urban tertiary care hospital and community hospital. PARTICIPANTS: Medical ICU survivors of mechanical ventilation aged 65 and older (N = 125). MEASUREMENTS: Baseline measurements of the Edmonton Symptom Assessment Scale (ESAS), categorized as mild (0-3), moderate (4-6), and severe (7-10), and the frailty phenotype were made during the week before hospital discharge. Functional recovery was defined as a return to a Katz activity of daily living dependency count less than or equal to the prehospitalization dependency count within 3 months. In the last 29 participants recruited, we made additional assessments of fatigue and ESAS both at baseline and 1 month after discharge. RESULTS: Fatigue was the most-prevalent moderate to severe symptom (74%), followed by dyspnea (53%), drowsiness (50%), poor appetite (47%), pain (45%), depression (42%), anxiety (36%), and nausea (17%). At 1-month follow-up, there were no significant differences in the proportions of participants with moderate to severe symptoms. Each increase in baseline ESAS fatigue severity category was associated with 55% lower odds of functional recovery (odds ratio = 0.45, 95% confidence interval = 0.24-0.84), independent of age, sex, comorbidities, and critical illness severity. Frail participants had a higher median baseline total ESAS symptom distress score (34, interquartile range (IQR) 23-44) than nonfrail participants (13, IQR 9-22) (P < .001). CONCLUSION: Older ICU survivors have a high burden of palliative care needs that persist 1 month after discharge. Fatigue is the most-prevalent symptom and may interfere with recovery. Post-ICU frailty may be a useful trigger for palliative care consultation and a treatment target.

High burden of palliative needs among older intensive care unit survivors transferred to post-acute care facilities. a single-center study.

RATIONALE: Adults with chronic critical illness (tracheostomy after ≥ 10 d of mechanical ventilation) have a high burden of palliative needs, but little is known about the actual use and potential need of palliative care services for the larger population of older intensive care unit (ICU) survivors discharged to post-acute care facilities. OBJECTIVES: To determine whether older ICU survivors discharged to post-acute care facilities have potentially unmet palliative care needs. METHODS: We examined electronic records from a 1-year cohort of 228 consecutive adults ≥ 65 years of age who had their first medical-ICU admission in 2009 at a single tertiary-care medical center and survived to discharge to a post-acute care facility (excluding hospice). Use of palliative care services was defined as having received a palliative care consultation. Potential palliative care needs were defined as patient characteristics suggestive of physical or psychological symptom distress or anticipated poor prognosis. We examined the prevalence of potential palliative needs and 6-month mortality. MEASUREMENTS AND MAIN RESULTS: The median age was 78 years (interquartile range, 71-84 yr), and 54% received mechanical ventilation for a median of 7 days (interquartile range, 3-16 d). Six subjects (2.6%) received a palliative care consultation during the hospitalization. However, 88% had at least one potential palliative care need; 22% had chronic wounds, 37% were discharged on supplemental oxygen, 17% received chaplaincy services, 23% preferred to not be resuscitated, and 8% were designated "comfort care." The 6-month mortality was 40%. CONCLUSIONS: Older ICU survivors from a single center who required postacute facility care had a high burden of palliative care needs and a high 6-month mortality. The in-hospital postcritical acute care period should be targeted for palliative care assessment and intervention.

A prognostic model for 6-month mortality in elderly survivors of critical illness.

BACKGROUND: Although 1.4 million elderly Americans survive hospitalization involving intensive care annually, many are at risk for early mortality following discharge. No models that predict the likelihood of death after discharge exist explicitly for this population. Therefore, we derived and externally validated a 6-month postdischarge mortality prediction model for elderly ICU survivors. METHODS: We derived the model from medical record and claims data for 1,526 consecutive patients aged ≥ 65 years who had their first medical ICU admission in 2006 to 2009 at a tertiary-care hospital and survived to discharge (excluding those patients discharged to hospice). We then validated the model in 1,010 patients from a different tertiary-care hospital. RESULTS: Six-month mortality was 27.3% and 30.2% in the derivation and validation cohorts, respectively. Independent predictors of mortality (in descending order of contribution to the model's predictive power) were a do-not-resuscitate order, older age, burden of comorbidity, admission from or discharge to a skilled-care facility, hospital length of stay, principal diagnoses of sepsis and hematologic malignancy, and male sex. For the derivation and external validation cohorts, the area under the receiver operating characteristic curve was 0.80 (SE, 0.01) and 0.71 (SE, 0.02), respectively, with good calibration for both (P = 0.31 and 0.43). CONCLUSIONS: Clinical variables available at hospital discharge can help predict 6-month mortality for elderly ICU survivors. Variables that capture elements of frailty, disability, the burden of comorbidity, and patient preferences regarding resuscitation during the hospitalization contribute most to this model's predictive power. The model could aid providers in counseling elderly ICU survivors at high risk of death and their families.