Arturo Briva

Spectral phasor analysis of LAURDAN fluorescence in live A549 lung cells to study the hydration and time evolution of intracellular lamellar body-like structures

Using LAURDAN spectral imaging and spectral phasor analysis we concurrently studied the growth and hydration state of subcellular organelles (lamellar body-like, LB-like) from live A549 lung cancer cells at different post-confluence days. Our results reveal a time dependent two-step process governing the size and hydration of these intracellular LB-like structures. Specifically, a first step (days 1 to 7) is characterized by an increase in their size, followed by a second one (days 7 to 14) where the organelles display a decrease in their global hydration properties. Interestingly, our results also show that their hydration properties significantly differ from those observed in well-characterized artificial lamellar model membranes, challenging the notion that a pure lamellar membrane organization is present in these organelles at intracellular conditions. Finally, these LB-like structures show a significant increase in their hydration state upon secretion, suggesting a relevant role of entropy during this process.

Adenosine triphosphate–dependent calcium signaling during ventilator-induced lung injury is amplified by hypercapnia

ABSTRACT Adenosine triphosphate (ATP) is released by alveolar epithelial cells during ventilator-induced lung injury (VILI) and regulates fluid transport across epithelia. High CO2 levels are observed in patients with “permissive hypercapnia,” which inhibits alveolar fluid reabsorption (AFR) in alveolar epithelial cells. The authors set out to determine whether VILI affects AFR and whether the purinergic pathway is modulated in cells exposed to hypercapnia. Control group was compared against VILI (tidal volume [Vt] = 35 mL/kg, zero positive end-expiratory pressure [PEEP]) and protective ventilation (Vt = 6 mL/kg, PEEP = 10 cm H2O) groups. Lung mechanics, histology, and AFR were evaluated. Alveolar epithelial cells (AECs) were loaded with Fura 2-AM to measure intracellular calcium in the presence ATP (10 μM) at 5% or 10% CO2 as compared with baseline. High tidal volume ventilation impairs lung mechanics and AFR. Hypercapnia (HC) increases intracellular calcium levels in response to ATP stimulation. HC + ATP is the most detrimental combination decreasing AFR. Purinergic signaling in AECs is modulated by high CO2 levels via increased cytosolic calcium. The authors reason that this modulation may play a role in the impairment of alveolar epithelial functions induced by hypercapnia.

Fatal acute pancreatitis complicated by pancreatic pseudocysts in a patient with systemic lupus erythematosus

Pancreatitis is a relatively rare but severe manifestation in systemic lupus erythematosus (SLE) patients. We report a case of a 39-year-old woman with previous SLE diagnose treated with prednisone and mycophenolate mofetil who developed an acute pancreatitis complicated by pancreatic pseudocysts within the context of a severe lupus flare. Elevated serum amylase and computerized tomography confirmed the diagnosis and mechanical obstruction or toxic-metabolic etiologies were ruled out. In the present case, we opted for the clinical surveillance of pancreatic pseudocyst and not perform invasive medical procedures to drainage. A steroid therapy was started in order to achieve SLE and pancreatitis remission, however, it was unable to avoid the development of multiorgan failure and patient died a few days after diagnosis was made.

Organizational Issues, Structure, and Processes of Care in 257 Icus in Latin America: A Study From the Latin America Intensive Care Network

Objective: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs. Design: Web-based survey submitted to ICU directors. Settings: ICUs located in nine Latin-American countries. Subjects: Individual ICUs. Interventions: None. Measurements and Main Results: Two hundred fifty-seven of 498 (52%) of submitted surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5% Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine percent of participating hospitals had less than 500 beds; most were public (59%) and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient ratio of 1 ≥ 2.1. The 24/7 presence of other specialists was deficient. Protocols in use averaged 9 ± 3. Brazil (vs the rest) had larger hospitals and ICUs and more quality, surveillance, and prevention committees, but fewer 24/7 intensivists and poorer nurse-to-patient ratio. Although standard monitoring, laboratory, and imaging practices were almost universal, more complex measurements and treatments and portable equipment were scarce after standard working hours, and in public hospitals. Mortality was 17.8%, without differences between countries. Conclusions: This multinational study shows major concerns in the delivery of critical care across Latin America, particularly in human resources. Technology was suboptimal, especially in public hospitals. A 24/7 availability of supporting specialists and of key procedures was inadequate. Mortality was high in comparison to high-income countries.

[Permissive and non-permissive hypercapnia: mechanisms of action and consequences of high carbon dioxide levels].

Acute lung injury is a disease with high mortality, which affects a large numbers of patients whose treatment continues to be debated. It has recently been postulated that hypercapnia can attenuate the inflammatory response during lung injury, which would assign it a specific role within lung protection strategies during mechanical ventilation. In this paper, we review current evidence on the role that high levels of CO2 in the blood play in lung injury. We conclude that, although there are reports that show benefits, the most recent evidence suggests that hypercapnia can be harmful and can contribute to worsening lung damage.

Picking Up the Pieces: Towards a Better Future for Critical Care Medicine in Three South American Countries

The demand for intensivists is increasing around the world, not only to meet the needs of a growing aging population, but also to fill positions in the intensive care unit now occupied by other specialists, since there is compelling evidence that the presence of critical care practitioners improves patient outcomes. Notwithstanding this, the shortage of intensivists is a problem recognized throughout the world. In this article, we discuss these issues in Argentina, Brazil, and Uruguay, three upper-middle income Latin American countries where critical care has been a medical specialty for decades and intensive care unit coverage traditionally has followed the 24/7 model. The lack of intensivists is multifactorial: the specialty is not taught to medical students; there is a general perception of a negative lifestyle compared with the practice of other medical specialties, due mainly to the constant 24-hour shift work; and there is general dissatisfaction with incomes, which has forced many intensivists into multijob schemes. The expected-and feared-consequences are the 40 to 70% vacant posts in residencies of critical care. Despite these drawbacks, scientific societies and colleges are intensely committed, pointing out these problems to the press, calling the health authorities for action, and permanently generating educational activities. Surprisingly, 83% of surveyed intensivists would choose critical care medicine again, evidencing the strong vocational component in its practice, which seems to predominate over negative aspects.