Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness.

INTRODUCTION: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients. METHODS: This was a single-center, prospective observational study enrolling SARS-CoV-2-positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-factor Xa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using χ2 tests. Multivariable logistic regression was used to determine the association between AT activity and mortality. RESULTS: In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP). CONCLUSION: Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies.

Association Between Early Tracheostomy and Delirium in Older Adults in the United States.

OBJECTIVES: Early tracheostomy (fewer than eight days after intubation) is associated with shorter length of stay in the intensive care unit and shorter duration of mechanical ventilation. Studies assessing the association between early tracheostomy and incidence of delirium, however, are lacking. This investigation sought to fill this gap. DESIGN: Retrospective cross-sectional study. SETTING: Multi-institutional acute care facilities in the United States. PARTICIPANTS: Data were derived from the National Inpatient Sample data from 2010 to 2014. Included patients were 65 or older and underwent both intubation and tracheostomy during the hospitalization. The authors excluded patients who underwent multiple intubations or tracheostomy procedures. INTERVENTIONS: Early tracheostomy versus non-early tracheostomy. RESULTS: In total, 23,310 patients were included, of whom 24.8% underwent early tracheostomy. From multivariate logistic regression, early tracheostomy was associated with lower odds of having a delirium diagnosis (odds ratio [OR] 0.77, p < 0.00001) across all admission classifications. Upon subgroup analysis, early tracheostomy was associated significantly with lower odds of having delirium for patients admitted with medical (OR 0.74, p < 0.00001) and nonsurgical injury admissions (OR 0.74, p = 0.00116). CONCLUSIONS: Early tracheostomy was associated significantly with lower odds of delirium among all patients studied. This association held true across medical and nonsurgical subgroups.

Determinants of pre-transplantation pectoralis muscle area (PMA) and post-transplantation change in PMA in lung transplant recipients.

BACKGROUND: This study aimed to determine predictors of pectoralis muscle area (PMA) and assess change in PMA following lung transplantation and its relationship to outcomes. METHODS: A retrospective review of 88 lung transplant recipients at a single center was performed. PMA was determined on a single axial slice from chest computerized tomography. Pectoralis muscle index (PMI) was calculated from the PMA divided by the height squared. RESULTS: PMI decreased post-transplantation (8.1±2.8 cm2 /m2 pre-transplantation, 7.5±2.9 cm2 /m2 at 6 months, and 7.6±2.7 cm2 /m2 at 12 months, P<.05). Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) were predictors of pre-transplant PMI (ß=-2.3, P=.001 for COPD; ß=2.1, P<.001 for ILD) and percent change in PMI at 12 months post-transplantation relative to baseline (ß=19.2, P=.04 for COPD; ß=-20.1, P=.01 for ILD). Patients in the highest quartile for PMI change at 12 months had fewer ventilator days compared with patients in the other quartiles (P=.03). CONCLUSIONS: Underlying diagnosis was a significant predictor of both pre-transplantation PMI and change in PMI post-transplantation. Further studies of PMI are needed to determine its clinical utility in predicting outcomes following lung transplantation.

Indications for lung transplant referral and listing.

Lung transplantation is a valuable therapeutic option for many patients with severe lung disease who have exhausted other medical or surgical therapies. However, since lungs are not a manufacturable organ like artificial heart valves or left ventricular assist devices, and since they are a limited resource compared to number of patients requiring the organs, the Department of Health and Human Services set the Final Rule of organ allocation in 1998. This led to development and implementation of Lung Allocation Score (LAS) in 2005. The score broadly divides lung diseases into 4 diagnostic criteria with a coefficient factor given to each category. The score is based on the prognostic factors of each patient to determine the risk of mortality without a transplant combined with the probability of patient survival post-transplant. Most of the guidelines for "Indications for referral and listing in lung transplant" is based on consensus opinion as there is limited amount of robust data and trials about this topic. The International Society for Heart and Lung Transplant (ISHLT) has published three editions for candidate selection and listing. In this article, we have attempted to highlight the guidelines and incorporated other disease specific prognostic factors that are not captured in the LAS. Ultimately, there are other factors like geographic location, height, blood group, preformed antibodies, transplant center experience, past wait times and transplant rate, availability of organs, etc., which also play a role especially when considering listing a patient for lung transplant. We also highlighted a representative disease in each category and most criteria for that disease will apply to other diseases in that category. Finally, this article does not delve into the history and reasoning behind each guideline but is meant to provide a general overview of indications and contraindications applicable in the field of adult lung transplantation.

Budesonide/formoterol combination in COPD: a US perspective.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease of the lung caused primarily by exposure to cigarette smoke. Clinically, it presents with progressive cough, sputum production, dyspnea, reduced exercise capacity, and diminished quality of life. Physiologically, it is characterized by the presence of partially reversible expiratory airflow limitation and hyperinflation. Pathologically, COPD is a multicomponent disease characterized by bronchial submucosal mucous gland hypertrophy, bronchiolar mucosal hyperplasia, increased luminal inflammatory mucus, airway wall inflammation and scarring, and alveolar wall damage and destruction. Management of COPD involves both pharmacological and nonpharmacological approaches. Bronchodilators and inhaled corticosteroids are recommended medications for management of COPD especially in more severe disease. Combination therapies containing these medications are now available for the chronic management of stable COPD. The US Food and Drug Administration, recently, approved the combination of budesonide/formoterol (160/4.5 µg; Symbicort™, AstraZeneca, Sweden) delivered via a pressurized meter dose inhaler for maintenance management of stable COPD. The combination also is delivered via dry powder inhaler (Symbicort™ and Turbuhaler™, AstraZeneca, Sweden) but is not approved for use in the United States. In this review, we evaluate available data of the efficacy and safety of this combination in patients with COPD.