Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials.

Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials.

Life-sustaining treatment decisions in the ICU for patients with ESLD: a prospective investigation.

We conducted a prospective study in the ICU of life-sustaining treatment and comfort care decisions over time in patients with end-stage liver disease (ESLD) from the perspectives of patients, family members, and healthcare professionals. Six patients with ESLD, 19 family members, and 122 professionals participated. The overarching theme describing the decision-making process was "on the train." Four sub-themes positioned patients and family members as passengers with limited control, unable to fully understand the decision-making process. Findings suggest that including patients and family members in non-immediate life-saving decisions and verifying early on their understanding may help to improve the decision-making process.

Co-presentation of pulmonary arteriovenous malformation (PAVM) and multifocal benign metastasizing leiomyoma (BML) of lungs: Diagnostic dilemma and successful endovascular treatment.

A 50-year-old female with a 20-year history of multifocal pulmonary benign metastasizing leiomyoma (BML), and asthma presented with subacute worsening of chronic dyspnea. A contrast-enhanced computerized tomography of the chest showed a single 1.4 × 1.5-cm contrast-enhancing mass in the right lower lobe among numerous non-enhancing bilateral pulmonary BML lesions. Pulmonary angiogram was not performed at that time due to clinical improvement. Four years later, the patient presented with refractory subacute worsening of her chronic dyspnea and was referred for embolization of the pulmonary arteriovenous malformation (PAVM). Two feeder arteries to the PAVM were embolized; each with a 6-mm Amplatzer-IV vascular plug and a 4-mm Nester coil. Follow-up angiograms demonstrated no flow through the PAVM. The patient's dyspnea resolved and she remained asymptomatic at one-year follow-up.

Randomized clinical trial of activated protein C for the treatment of acute lung injury.

RATIONALE: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. OBJECTIVES: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. METHODS: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days. MEASUREMENTS AND MAIN RESULTS: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups. CONCLUSIONS: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity.

Extravascular lung water in sepsis-associated acute respiratory distress syndrome: indexing with predicted body weight improves correlation with severity of illness and survival.

OBJECTIVES: To determine whether extravascular lung water predicts survival in patients with early acute respiratory distress syndrome, to determine the relationship between extravascular lung water and other markers of lung injury, and to examine if indexing extravascular lung water with predicted body weight (EVLWp) strengthens its discriminative power. DESIGN: Extravascular lung water and other markers of lung injury were measured prospectively in 19 patients with sepsis-induced acute respiratory distress syndrome for 3 days. SETTING: The intensive care units of an academic tertiary referral hospital. MEASUREMENTS AND MAIN RESULTS: Lung injury score, Sequential Organ Failure Assessment score, dead space-tidal volume fraction (Vd/Vt), and EVLWp were all significantly higher on day 1 in nonsurvivors compared with survivors (lung injury score, 2.8 +/- 0.34 vs. 1.9 +/- 0.50; p = .004) (Sequential Organ Failure Assessment score, 13 +/- 3.4 vs. 7.7 +/- 0.8; p = .006) (Vd/Vt, 0.68 +/- 0.07 vs. 0.58 +/- 0.07; p = .009) (EVLWp, 20.6 +/- 4.6 vs. 11.6 +/- 1.9 mL/kg; p = .002). EVLWp correlated with Sequential Organ Failure Assessment score, lung injury score, Vd/Vt, and PaO2/FIO2. The receiver operator characteristic curve analysis indicated that EVLWp, Vd/Vt, and extravascular lung water (p = .0005, .009, and .013, respectively) but not PaO2/FIO2 (p = .311) discriminate between survivors and nonsurvivors. Three-day average EVLWp >16 mL/kg predicted in-hospital mortality with 100% specificity and 86% sensitivity. CONCLUSIONS: Increased extravascular lung water is a feature of early acute respiratory distress syndrome and predicts survival. Indexing extravascular lung water to predicted body weight, instead of actual body weight, improves the predictive value of extravascular lung water for survival and correlation with markers of disease severity.

Extraction of dental crowns from the airway: a multidisciplinary approach.

We describe two cases of airway foreign bodies (FB) consisting of a dental crown. The shape and composition of dental crowns complicate their extraction from the tracheobronchial tree, sometimes necessitating thoracotomy. We describe the use of a multidisciplinary approach involving rigid and flexible bronchoscopy in concert with the use of wire snares under fluoroscopic guidance for extraction of these challenging FB. These cases illustrate that this multidisciplinary approach can allow successful extraction of the difficult FB from much of the tracheobronchial tree and the avoidance of thoracotomy.

Management of asthma exacerbations.

The 1997 Expert Panel Report 2 from the National Asthma Education and Prevention Program* details principles and goals for managing asthma exacerbations, based on scientific literature and the opinion of the panel. The panel's recommendations are summarized here, along with approaches to the evaluation and management of patients with asthma exacerbations. Methods to assess and classify the severity of asthma exacerbations are discussed, and treatment objectives for mild, moderate, and severe exacerbations are presented, along with a discussion of postinfectious acute airway hyperresponsiveness. A review of pharmacologic agents used in the treatment of asthma exacerbations is also included. Key points in the management of asthma exacerbations include the notion that early treatment is the best strategy for management. Important elements of early treatment include recognition of early signs of worsening asthma, a written action plan to guide patient self-management, appropriate intensification of therapy, and prompt communication between patient and provider about deterioration in asthma control. Other key points include the use of inhaled beta 2-adrenergic agonists to provide prompt relief of airflow obstruction, the early use of systemic corticosteroids for patients with moderate to severe exacerbations or for patients who fail to respond promptly and completely to an inhaled beta 2-adrenergic agonist, and monitoring response to therapy with serial measurements of lung function.

Prevalence of left heart contrast in healthy, young, asymptomatic humans at rest breathing room air.

Our purpose was to report the prevalence of healthy, young, asymptomatic humans who demonstrate left heart contrast at rest, breathing room air. We evaluated 176 subjects (18-41 years old) using transthoracic saline contrast echocardiography. Left heart contrast appearing ≤3 cardiac cycles, consistent with a patent foramen ovale (PFO), was detected in 67 (38%) subjects. Left heart contrast appearing >3 cardiac cycles, consistent with the transpulmonary passage of contrast, was detected in 49 (28%) subjects. Of these 49 subjects, 31 were re-evaluated after breathing 100% O2 for 10-15min and 6 (19%) continued to demonstrate the transpulmonary passage of contrast. Additionally, 18 of these 49 subjects were re-evaluated in the upright position and 1 (5%) continued to demonstrate the transpulmonary passage of contrast. These data suggest that ~30% of healthy, young, asymptomatic subjects demonstrate the transpulmonary passage of contrast at rest which is reduced by breathing 100% O2 and assuming an upright body position.

Communication by nurses in the intensive care unit: qualitative analysis of domains of patient-centered care.

BACKGROUND: High-quality communication is a key determinant and facilitator of patient-centered care. Nurses engage in most of the communication with patients and patients' families in the intensive care unit. OBJECTIVE: To perform a qualitative analysis of nurses' communications. METHODS: Ethnographic observations of 315 hours of interactions and 53 semistructured interviews with 33 nurses were conducted in a 26-bed cardiac-medical intensive care unit in an academic hospital and a 26-bed general intensive care unit in a Veterans Affairs hospital in Portland, Oregon. Communication interactions were categorized into 5 domains of patient-centered care. Interviews were analyzed to identify major themes in nurses' roles and preferences for communicating with patients and patients' families within the domains. RESULTS: Most communication occurred in the domains of biopsychosocial information exchange, patient as person, and clinician as person. Nurses endorsed the importance of the domains of shared power and responsibility and therapeutic alliance but had relatively few communication interactions in these areas. Communication behaviors were strongly influenced by the nurses' roles as translators of information between physicians and patients and the patients' families and what the nurses were and were not willing to communicate to patients and patients' families. CONCLUSIONS: Critical care, including communication, is a collaborative effort. Understanding how nurses engage in patient-centered communication in the intensive care unit can guide future interventions to improve patient-centered care.