Association of obesity on the outcome of critically ill patients affected by COVID-19.

OBJECTIVE: To evaluate the impact of obesity on ICU mortality. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adults patients admitted with COVID-19 and respiratory failure. INTERVENTIONS: None. PRIMARY VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. Body mass index (BMI) impact on ICU mortality was studied as (1) a continuous variable, (2) a categorical variable obesity/non-obesity, and (3) as categories defined a priori: underweight, normal, overweight, obesity and Class III obesity. The impact of obesity on mortality was assessed by multiple logistic regression and Smooth Restricted cubic (SRC) splines for Cox hazard regression. RESULTS: 5,206 patients were included, 20 patients (0.4%) as underweight, 887(17.0%) as normal, 2390(46%) as overweight, 1672(32.1) as obese and 237(4.5%) as class III obesity. The obesity group patients (n = 1909) were younger (61 vs. 65 years, p < 0.001) and with lower severity scores APACHE II (13 [9-17] vs. 13[10-17, p < 0.01) than non-obese. Overall ICU mortality was 28.5% and not different for obese (28.9%) or non-obese (28.3%, p = 0.65). Only Class III obesity (OR = 2.19, 95%CI 1.44-3.34) was associated with ICU mortality in the multivariate and SRC analysis. CONCLUSIONS: COVID-19 patients with a BMI > 40 are at high risk of poor outcomes in the ICU. An effective vaccination schedule and prolonged social distancing should be recommended.

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.

PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.

Pulmonary Aspergillosis: Spectrum of Disease.

Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.

Antibiotic Timing and Outcomes in Sepsis.

BACKGROUND: We evaluated the effect of time spent in the emergency department (ED) and process of care on mortality and length of hospital stay in patients with sepsis or septic shock. METHODS: An observational cohort study was conducted on 117 patients who came through the University of Louisville Hospital ED and subsequently were directly admitted to the intensive care unit (ICU). Variables of interest were time in the ED from triage to physical transport to the ICU, from triage to antibiotic(s) ordered, and from triage to antibiotic(s) administered. Expected mortality was calculated according to the University Health System Consortium Database. Primary and secondary outcomes were in-hospital death and hospital length of stay in days, respectively. RESULTS: We found no significant association between time in the ED and mortality between survivors and nonsurvivors (5.5 versus 5.7 hours, P = 0.804). After adjusting for expected mortality, a 22% increase in mortality risk was found for each hour delay from triage to antibiotic(s) ordered; a 15% increase in mortality risk was observed for each hour from triage to antibiotic(s) given. Both time from triage to antibiotic(s) ordered (hazard ratio [HR] = 0.8, P = 0.044) and time from triage to antibiotic(s) delivery (HR = 0.79, P = 0.0092) were independently associated with an increased hospital stay (HR = 0.79, P = 0.0092). CONCLUSION: Though no significant association between mortality and ED time was demonstrated, we observed a significant increase in mortality in septic patients with both delays in antibiotic(s) order and administration. Delay in care also resulted in increased hospital stays both overall and in the ICU.

Alcohol y síndrome de distrés respiratorio agudo: ¿casualidad o causalidad? / Alcohol and acute respiratory distress syndrome: casuality or causality?

Esta revisión se ocupa de la asociación entre alcoholismo y lesión pulmonar aguda/SDRA y pretende explicar su fisiopatología, señalando posibles implicaciones terapéuticas. El alcohol se considera un importante factor de riesgo en el desarrollo de neumonía desde hace más de un siglo, pero hasta fecha reciente no se creía que tuviera efectos relevantes sobre la función y estructura pulmonares. Sin embargo, estudios epidemiológicos y de experimentación animal han revelado que el alcoholismo aumenta en 2 a 4 veces el riesgo de síndrome de distrés respiratorio agudo (SDRA) en pacientes con sepsis o politraumatismo, y puede desempeñar en más del 50% de casos un papel en la patogenia de este síndrome. Aunque el alcoholismo por sí solo no causa lesión pulmonar aguda, predispone a la disfunción pulmonar en respuesta al estrés inflamatorio presente en situaciones clínicas reconocidas como causa de SDRA, facilitando su desarrollo y empeorando su evolución. Recientes investigaciones realizadas tanto en modelos animales alimentados con etanol, como en humanos con antecedentes de alcoholismo, constatan esta conexión previamente no reconocida entre alcohol y lesión pulmonar aguda y han puesto al descubierto numerosas alteraciones que hoy se conocen como el «pulmón del alcohólico» (AU)

Alcohol has been considered an important risk factor for the development of pneumonia since the last century. Nevertheless, it was not thought that it had relevant effects on lung structure and functions until recently. Recent studies have shown that the risk for acute respiratory distress syndrome (ARDS) is 2-4 times higher among alcoholic patients with sepsis or trauma, and that alcoholism can play a roll in more than 50% of cases in the pathogenesis of this syndrome. Although alcoholism per se does not cause acute lung injury it predisposes to pulmonary dysfunction after inflammatory stress, that is present in clinical situations that cause ARDS leading to its development and complicating its outcome. Recent investigations in animals and humans with alcohol abuse have uncovered several alterations currently known as the “alcoholic lung”. This revision discusses the association between alcohol abuse and lung injury/ARDS and tries to explain the physiopathology along with possible treatments (AU)

[Alcohol and acute respiratory distress syndrome: casuality or causality?]. / Alcohol y síndrome de distrés respiratorio agudo:¿casualidad o causalidad?

Alcohol has been considered an important risk factor for the development of pneumonia since the last century. Nevertheless, it was not thought that it had relevant effects on lung structure and functions until recently. Recent studies have shown that the risk for acute respiratory distress syndrome (ARDS) is 2-4 times higher among alcoholic patients with sepsis or trauma, and that alcoholism can play a roll in more than 50% of cases in the pathogenesis of this syndrome. Although alcoholism per se does not cause acute lung injury it predisposes to pulmonary dysfunction after inflammatory stress, that is present in clinical situations that cause ARDS leading to its development and complicating its outcome. Recent investigations in animals and humans with alcohol abuse have uncovered several alterations currently known as the "alcoholic lung". This revision discusses the association between alcohol abuse and lung injury/ARDS and tries to explain the physiopathology along with possible treatments.

Discrepancy between clinical criteria for diagnosing acute respiratory distress syndrome secondary to community acquired pneumonia with autopsy findings of diffuse alveolar damage.

Diffuse alveolar damage (DAD) is the underlying pathological finding in most cases of acute respiratory distress syndrome (ARDS). The objective of this study was to compare clinical criteria for ARDS secondary to community acquired pneumonia with autopsy findings of DAD and to determine the discrepancy rate between the two. We compared prospectively obtained clinical diagnosis of ARDS secondary to community acquired pneumonia with autopsy findings of DAD and pneumonia. Forty nine patients dead with a clinical diagnosis of ARDS secondary to pneumonia who underwent autopsy between 1986 and 2004 in our ICU were included with systematic histopathological analysis of all lung lobes. The discrepancy rate between the premortem clinical diagnosis of ARDS secondary to pneumonia and DAD at autopsy was determined. Seven patients were found to have neither infection nor DAD at autopsy. Six patients showed pathologic signs of DAD without evidence of infection. Out of 38 patients meeting clinical criteria for ARDS secondary to pneumonia and proven pneumonia at autopsy, 25 met criteria for DAD at autopsy. Therefore, 18 out of 49 patients who were clinically diagnosed with ARDS did not actually show pathological signs of DAD, resulting in a discrepancy rate of 37%. Despite an acceptable correspondence between clinical criteria for ARDS secondary to pneumonia and autopsy findings of DAD a significant number of patients had neither signs of DAD nor infection.

Airway nociceptors activated by pro-inflammatory cytokines.

The present studies evaluate whether the vagus nerves link the lungs' immune and neural systems by transmitting information through pulmonary nociceptors. Single unit activities from pulmonary nociceptors [C fiber receptors (CFRs) and high threshold Adelta fiber receptors (HTARs)] were recorded from the cervical vagus nerve in anesthetized, open-chest, and mechanically ventilated rabbits. Interleukin1beta was then injected into the nociceptor field (IL-1beta, 10 microg/ml, 20 microl). Both CFRs and HTARs were stimulated by the local injection; their activities increased from 0.2+/-0.1 to 1.8+/-0.5 imp/s (n=10; p<0.01), and from 0.2+/-0.1 to 1.1+/-0.1 imp/s, respectively (n=6; p<0.01). These increases were greatly attenuated by simultaneous administration of IL-1beta with IL-1 ra, a natural IL-1 receptor antagonist. The nociceptors were not stimulated by local injection of normal saline. Our data demonstrate that nociceptors can be activated by pro-inflammatory cytokines and support the hypothesis that airway nociceptors transmit immune signals from the lung to the brain.