Extubation Failure in Critically Ill COVID-19 Patients: Risk Factors and Impact on In-Hospital Mortality.

PURPOSE: We sought to identify clinical factors that predict extubation failure (reintubation) and its prognostic implications in critically ill COVID-19 patients. MATERIALS AND METHODS: Retrospective, multi-center cohort study of hospitalized COVID-19 patients. Multivariate competing risk models were employed to explore the rate of reintubation and its determining factors. RESULTS: Two hundred eighty-one extubated patients were included (mean age, 61.0 years [±13.9]; 54.8% male). Reintubation occurred in 93 (33.1%). In multivariate analysis accounting for death, reintubation risk increased with age (hazard ratio [HR] 1.04 per 1-year increase, 95% confidence interval [CI] 1.02 -1.06), vasopressors (HR 1.84, 95% CI 1.04-3.60), renal replacement (HR 2.01, 95% CI 1.22-3.29), maximum PEEP (HR 1.07 per 1-unit increase, 95% CI 1.02 -1.12), paralytics (HR 1.48, 95% CI 1.08-2.25) and requiring more than nasal cannula immediately post-extubation (HR 2.19, 95% CI 1.37-3.50). Reintubation was associated with higher mortality (36.6% vs 2.1%; P < 0.0001) and risk of inpatient death after adjusting for multiple factors (HR 23.2, 95% CI 6.45-83.33). Prone ventilation, corticosteroids, anticoagulation, remdesivir and tocilizumab did not impact the risk of reintubation or death. CONCLUSIONS: Up to 1 in 3 critically ill COVID-19 patients required reintubation. Older age, paralytics, high PEEP, need for greater respiratory support following extubation and non-pulmonary organ failure predicted reintubation. Extubation failure strongly predicted adverse outcomes.

Gradient changes in bioprosthetic valve thrombosis: duration of anticoagulation and strategies to improve detection.

OBJECTIVE: Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. METHODS: Patients treated with warfarin for BPVT (1999-2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation-BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size-BPVT diagnosis) and time-to-recovery (BPVT diagnosis-complete resolution) were recorded. RESULTS: 77 patients were identified; 32 (42%) aortic (23 surgical-12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). CONCLUSION: Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.

Safety of apixaban compared to warfarin in hemodialysis patients: Do antiplatelets make a difference?

BACKGROUND: Data on the safety of apixaban compared to warfarin in hemodialysis (HD) patients are accumulating, but the impact of concomitant antiplatelet use is unknown. OBJECTIVES: Compare hemorrhagic risk and impact of antiplatelets in HD patients receiving oral anticoagulants (OAC). METHODS: Retrospective, multi-center study of HD patients started on OAC inpatient over 5 years. RESULTS: 707 patients were included: 563 received warfarin, and 144 received apixaban. 197 had bleeding, most in the warfarin group (173 [30.1%] vs 24 [16.7%] in the apixaban group), P-value < .01). However, with concomitant antiplatelet use, frequencies were similar (31.4% vs 25.0%; P-value = .292). Cumulative incidence using bleeding as event of interest and death as competing risk showed higher rates of bleeding with warfarin. In a multivariate model, apixaban was associated with a lower hemorrhagic risk (hazard ratio [HR] 0.55 [95% confidence interval {CI} 0.35-0.86}). Apixaban showed lower hemorrhagic risk alone (HR 0.24, 95% CI 0.10-0.55) and similar risk when administered with antiplatelets (HR 0.93, 95% CI 0.55-1.56). CONCLUSIONS: Apixaban is associated with less bleeding in HD patients compared to warfarin, but concomitant antiplatelet use may negate the safety advantage. Prospective trials are warranted to determine the impact of antiplatelets on apixaban safety.

Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis.

BACKGROUND: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. OBJECTIVES: We evaluated the impact on survival of different AC doses in COVID-19 patients. METHODS: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. RESULTS: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. CONCLUSIONS: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.

Therapeutic Anticoagulation Delays Death in COVID-19 Patients: Cross-Sectional Analysis of a Prospective Cohort.

A hypercoagulable state has been described in coronavirus disease 2019 (COVID-19) patients. Others have reported a survival advantage with prophylactic anticoagulation (pAC) and therapeutic anticoagulation (tAC), but these retrospective analyses have important limitations such as confounding by indication. We studied the impact of tAC and pAC compared with no anticoagulation (AC) on time to death in COVID-19. We performed a cross-sectional analysis of 127 deceased COVID-19 patients and compared time to death in those who received tAC ( n = 67), pAC ( n = 47), and no AC ( n = 13). Median time to death was longer with higher doses of AC (11 days for tAC, 8 days for pAC, and 4 days for no AC, p < 0.001). In multivariate analysis, AC was associated with longer time to death, both at prophylactic (hazard ratio [HR] = 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.001) and therapeutic doses (HR = 0.15; 95% CI: 0.07 to 0.32; p < 0.001) compared with no AC. Bleeding rates were similar among tAC and remaining patients (19 vs. 18%; p = 0.877). In deceased COVID-19 patients, AC was associated with a delay in death in a dose-dependent manner. Randomized trials are required to prospectively investigate the benefit and safety of higher doses of AC in this population.

Unusual behaviour of an unusual tumour: calcitriol-induced hypercalcaemia in metastatic oesophageal neuroendocrine carcinoma.

Hypercalcaemia in malignancy is most commonly caused by paraneoplastic secretion of parathyroid hormone-related protein or osteolytic metastases. Very rarely (<1% of cases), the mechanism behind increased serum calcium is increased production of calcitriol (1,25-dihydroxyvitamin D) and even rarer is the occurrence of this phenomenon in solid malignancies, with few such instances reported in the literature. We present a case of a neuroendocrine malignancy originating in the oesophagus associated with calcitriol-induced hypercalcaemia, a phenomenon that has not been previously described. We review the pathophysiology of calcitriol-induced hypercalcaemia and previously reported cases of solid tumours with this presentation.

Long-Term Outcomes of Anticoagulation for Bioprosthetic Valve Thrombosis.

BACKGROUND: Early in the prevention and treatment of bioprosthetic valve thrombosis (BPVT), anticoagulation is effective, but the long-term outcome after BPVT is unknown. OBJECTIVES: The goal of this study was to assess the long-term outcomes of patients with BPVT treated with anticoagulation. METHODS: This analysis was a matched cohort study of patients treated with warfarin for suspected BPVT at the Mayo Clinic between 1999 and 2017. RESULTS: A total of 83 patients treated with warfarin for suspected BPVT (age 57 ± 18 years; 45 men [54%]) were matched to 166 control subjects; matching was performed according to age, sex, year of implantation, and prosthesis type and position. Echocardiography normalized in 62 patients (75%) within 3 months (interquartile range [IQR]: 1.5 to 6 months) of anticoagulation; 21 patients (25%) did not respond to warfarin. Median follow-up after diagnosis was 34 months (IQR: 17 to 54 months). There was no difference in the primary composite endpoint between the patients with BPVT and the matched control subjects (log-rank test, p = 0.79), but the former did have a significantly higher rate of major bleeding (12% vs. 2%; p < 0.0001). BPVT recurred (re-BPVT) in 14 (23%) responders after a median of 23 months (IQR: 11 to 39 months); all but one re-BPVT patient responded to anticoagulant therapy. Patients with BPVT had a higher probability of valve re-replacement (68% vs. 24% at 10 years' post-BPVT; log-rank test, p < 0.001). CONCLUSIONS: BPVT was associated with re-BPVT and early prosthetic degeneration in a significant number of patients. Indefinite warfarin anticoagulation should be considered after a confirmed BPVT episode, but this strategy must be balanced against an increased risk of bleeding.

Prognostic Importance and Predictors of Survival in Isolated Tricuspid Regurgitation: A Growing Problem.

OBJECTIVE: To define mortality associated with isolated tricuspid regurgitation (TR) and identify risk factors associated with decreased survival. PATIENTS AND METHODS: We conducted a retrospective cohort study of residents of southeastern Minnesota with moderate-severe or more severe isolated TR diagnosed between January 1, 2005, and April 15, 2015. Isolated TR was defined as TR in the absence of left-sided heart disease or pulmonary hypertension. Patients with an ejection fraction of less than 50%, right ventricular systolic pressure greater than 45 mm Hg, moderate or more severe left-sided valve disease, congenital cardiac anomalies, previous valve operation, tricuspid stenosis, flail leaflet, carcinoid, and rheumatic disease were excluded. Five-year survival was compared with age- and sex-matched Minnesota census bureau data. Multivariate regression was used to identify variables associated with mortality. RESULTS: Over a 10-year period, 289 patients with isolated TR were identified. The mean ± SD age was 79.2±10.6 years, 70.6% (204) were women, atrial fibrillation was present in 74.0% (214), and 24.6% (71) had an intracardiac device. By 5 years after diagnosis, 51.5% had been hospitalized for heart failure. Observed 5-year mortality was 47.8% compared with 36.3% in the census data (P=.005). After adjusting for age and other comorbidities, multivariate regression identified a dilated inferior vena cava (≥2.1 cm) without respiratory variation on echocardiography (hazard ratio, 1.93; 95% CI, 1.13-3.31; P=.02) and creatinine level greater than 1.6 mg/dL (hazard ratio, 1.8; 95% CI, 1.16-2.8; P=.009) as associated with increased mortality. CONCLUSION: Patients with isolated TR are frequently hospitalized for heart failure and experience excess mortality. Elevated right atrial pressure and renal dysfunction are associated with mortality. This poor outcome may have implications for timing of intervention.

Myocardial Stiffness by Intrinsic Cardiac Elastography in Patients with Amyloidosis: Comparison with Chamber Stiffness and Global Longitudinal Strain.

BACKGROUND: The aim of this study was to test the hypothesis that intrinsic cardiac elastography can detect diastolic tissue abnormalities produced by cardiac amyloid infiltration and that measurements may have incremental value beyond traditional echocardiographic measures. The specific aims were (1) to evaluate the relationship between left ventricular myocardial stiffness (by elastography) and measures of diastolic chamber stiffness and systolic strain in patients with amyloidosis and (2) to compare their prognostic potential. METHODS: We prospectively studied 67 patients with amyloidosis (cardiac amyloidosis, n = 48; noncardiac amyloidosis, n = 19) and 40 normal subjects. Patients underwent comprehensive echocardiography including measurement of left ventricular global longitudinal strain (GLS) by speckle-tracking. Intrinsic velocity propagation of myocardial stretch (iVP), a direct measure of myocardial elasticity, was quantified using intrinsic cardiac elastography. Chamber stiffness was evaluated from the end-diastolic pressure-volume relationships (P = αVß). The major end point at follow-up was the composite of death, cardiac hospitalization, worsening heart failure, and stroke. RESULTS: The iVP of myocardial stretch was highest in patients with cardiac amyloidosis compared with those with noncardiac amyloidosis and normal subjects (3.2 ± 1.0, 1.8 ± 0.4, and 1.6 ± 0.2 m/sec, respectively; P < .0001) and correlated with chamber stiffness, function, and structure (ß coefficient, operating chamber stiffness, GLS, wall thickness; P ≤ .001 for all). At follow-up (median, 2.6 years), measures of left ventricular and myocardial stiffness, GLS, diastolic dysfunction grade, and N-terminal pro-brain natriuretic peptide were associated with excess events. At multivariate analysis, iVP of myocardial stretch remained an independent predictor of adverse events, incremental to GLS and N-terminal pro-brain natriuretic peptide. CONCLUSIONS: Measurements by cardiac elastography correlate with functional and structural derangements produced by cardiac amyloid infiltration but provide unique information that is incremental to conventional echocardiography.

Reference Values for Mid-Ascending Aorta Diameters by Transthoracic Echocardiography in Adults.

We sought to characterize mid-ascending aorta diameter reference values by age, sex, and body surface area (BSA) in a large echocardiography laboratory practice-based cohort. All subjects with transthoracic echocardiograms with mid-ascending aorta diameter measure from January 2004 to December 2009 were identified, and medical records were reviewed for medical history and anthropometric data. Those with aortic valve disease or replacement, congenital heart disease, any connective tissue or inflammatory disease that may affect the aorta, or known aortic aneurysm (>55 mm) were excluded. Mid-ascending aorta diameter was measured in a standardized manner using "leading edge to leading edge" technique at end-diastole. Of 27,839 eligible subjects, 16,620 did not have history of hypertension and were included in the analysis (56.3% female; mean age 52.0 ± 15.8 years), mean mid-ascending aorta diameter 31.7 ± 4.1 mm. Females had smaller diameter than males (30.5 ± 3.7 mm vs 33.3 ± 4.0 mm; p <0.001). Subjects with history of hypertension (n = 11,219; not included in the analysis) had larger mid-ascending aorta diameter compared with normotensive subjects (33.9 ± 3.8 mm vs 31.7 ± 4.1 mm; p < 0.001). Age had the greatest correlation with aortic size (r = 0.55), followed by sex (r = 0.35) and BSA (r = 0.35). Nomograms for predicted mid-ascending aorta diameter were generated at the 95th percentile using quantile regression for subjects without hypertension stratified by age, sex, and BSA. In conclusion, mid-ascending aorta diameter is predominantly associated with sex, age, and BSA. The nomograms established by this study may serve as useful reference values for echocardiographic screening and surveillance.

Psychological effects of poetry workshops with people with early stage dementia: an exploratory study.

OBJECTIVE: The aim of this study was to test the effectiveness of writing poetry on psychological functioning in people with early stage dementia. METHOD: A series of poetry writing workshops was conducted with four women, at the end of which a one-on-one short structured interview was conducted. RESULTS: All of the women said that they benefited from the workshops, but their experiences differed greatly. Themes included competence and self-efficacy, personal growth, wanting to contribute and poetry writing as a way of coping with the progression of the condition. CONCLUSION: Creative activities such as writing poetry hold promise for enhancing the quality of life of people with dementia.