Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. OBJECTIVE: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. DESIGN: A prospective cohort study was carried out. SETTING: Intensive Care Unit of a tertiary hospital. PATIENTS: The first 22 consecutive COVID-19 deaths. MEASUREMENTS: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. RESULTS: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. LIMITATION: Limited sample size. CONCLUSIONS: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Histopathological features in fatal COVID-19 acute respiratory distress syndrome.

Background: COVID-19 acute respiratory distress syndrome (ARDS) shares the common histological hallmarks with other forms of ARDS. However, the chronology of the histological lesions has not been well established. Objective: To describe the chronological histopathological alterations in the lungs of patients with COVID-19 related ARDS. Design: A prospective cohort study was carried out. Setting: Intensive Care Unit of a tertiary hospital. Patients: The first 22 consecutive COVID-19 deaths. Measurements: Lung biopsies and histopathological analyses were performed in deceased patients with COVID-19 related ARDS. Clinical data and patient course were evaluated. Results: The median patient age was 66 [63-74] years; 73% were males. The median duration of mechanical ventilation was 17 [8-24] days. COVID-19 induced pulmonary injury was characterized by an exudative phase in the first week of the disease, followed by a proliferative/organizing phase in the second and third weeks, and finally an end-stage fibrosis phase after the third week. Viral RNA and proteins were detected in pneumocytes and macrophages in a very early stage of the disease, and were no longer detected after the second week. Limitation: Limited sample size. Conclusions: The chronological evolution of COVID-19 lung histopathological lesions seems to be similar to that seen in other forms of ARDS. In particular, lung lesions consistent with potentially corticosteroid-sensitive lesions are seen.

Antecedentes: El síndrome de dificultad respiratoria aguda (SDRA) asociado a la COVID-19 comparte características histológicas con otros tipos de SDRA. Sin embargo, no se ha establecido adecuadamente la cronología de las lesiones histológicas. Objetivo: Describir las alteraciones histopatológicas cronológicas en los pulmones de los pacientes con síndrome de dificultad respiratoria aguda asociado a COVID-19. Diseño: Estudio prospectivo de cohortes. Ámbito: Unidad de cuidados intensivos de un hospital terciario. Pacientes: Las primeras 22 muertes consecutivas por COVID-19. Intervenciones: Se llevaron a cabo biopsias pulmonares y análisis histopatológicos en pacientes fallecidos por SDRA asociado a COVID-19. Se evaluaron los datos clínicos y la evolución médica. Resultados: La mediana de edad de los pacientes fue de 66 (63-74) años y el 73% eran varones. La mediana de la duración de la ventilación mecánica fue de 17 (8-24) días. La lesión pulmonar inducida por COVID-19 se caracterizó por una fase exudativa durante la primera semana de la enfermedad, seguida de una fase proliferativa/organizativa en la segunda y tercera semana y, por último, una fase de fibrosis en fase terminal tras la tercera semana de evolución. Se detectaron proteínas y ARN vírico en neumocitos y macrófagos en una fase muy temprana de la enfermedad, pero estos ya no se volvieron a detectar a partir de la segunda semana. Limitación: Tamaño limitado de la muestra. Conclusión: La evolución cronológica de las lesiones histopatológicas pulmonares asociadas a la COVID-19 parece ser similar a la de otras formas de SDRA. En particular, se observan daños pulmonares coherentes con las lesiones potencialmente sensibles a los corticosteroides.

[Extracorporeal life support in thoracic surgery: What are the indications and the pertinence?] / Support extracorporel en chirurgie thoracique : quelles indications et quels intérêts ?

INTRODUCTION: In thoracic surgery, extracorporeal life support (ECLS) technologies are used in cases of severe and refractory respiratory failure or as intraoperative cardiorespiratory support. The objectives of this review are to describe the rationale of ECLS techniques, to review the pulmonary diseases potentially treated by ECLS, and finally to demonstrate the efficacy of ECLS, using recently published data from the literature, in order to practice evidence based medicine. STATE OF THE ART: ECLS technologies should only be undertaken in expert centers. ECLS allows a protective ventilatory strategy in severe ARDS. In the field of lung transplantation, ECLS may be used successfully as a bridge to transplantation, as intraoperative cardiorespiratory support or as a bridge to recovery in cases of severe primary graft dysfunction. In general thoracic surgery, ECLS technology seems to be safe and efficient as intraoperative respiratory support for tracheobronchial surgery or for severe respiratory insufficiency, without significant increase in perioperative risk. PERSPECTIVE: The indications for ECLS are going to increase. Future improvements both in scientific knowledge and bioengineering will improve the prognosis of patients treated with ECLS for respiratory failure. Multicenter randomized controlled trials will refine the indications for ECLS and improve the global care strategies for these patients. CONCLUSION: ECLS is an efficient therapeutic strategy that will improve the prognosis of patients suffering from, or exposed to, the risks of severe respiratory failure.

Outbreak of psittacosis in a group of women exposed to Chlamydia psittaci-infected chickens.

Eight cases of psittacosis due to Chlamydia psittaci were identified in May 2013 among 15 individuals involved in chicken gutting activities on a mixed poultry farm in France. All cases were women between 42 and 67 years-old. Cases were diagnosed by serology and PCR of respiratory samples. Appropriate treatment was immediately administered to the eight hospitalised individuals after exposure to birds had been discovered. In the chicken flocks, mainly C. gallinacea was detected, a new member of the family Chlamydiaceae, whereas the ducks were found to harbour predominantly C. psittaci, the classical agent of psittacosis. In addition, C. psittaci was found in the same flock as the chickens that the patients had slaughtered. Both human and C. psittaci-positive avian samples carried the same ompA genotype E/B of C. psittaci, which is widespread among French duck flocks. Repeated grassland rotations between duck and chicken flocks on the farm may explain the presence of C. psittaci in the chickens. Inspection by the veterinary service led to temporary closure of the farm. All birds had to be euthanised on site as no slaughterhouses accepted processing them. Farm buildings and grasslands were cleaned and/or disinfected before the introduction of new poultry birds.

Resistive Index or color-Doppler semi-quantitative evaluation of renal perfusion by inexperienced physicians: results of a pilot study.

BACKGROUND: Doppler-based renal resistive index (RI) calculation may help in the early detection of acute kidney injury (AKI). Its feasibility and reproducibility by inexperienced operators remain unknown. The main objective of this study was to compare performances of junior and senior operators in assessing renal perfusion using both the semiquantitative color-Doppler scale and RI calculation. METHODS: Prospective cohort study performed in 3 ICUs. Inexperienced juniors physicians attended a half-day course on renal perfusion assessment using RI calculation and color-Doppler (from 0, absence of renal perfusion; to 3, renal vessels identifiable in the entire field of view). Junior and senior operators used both methods in 69 mechanically ventilated patients, in blind fashion. RESULTS: Failure to obtain RI occurred for a junior operator in a single patient. RI and color-Doppler semi-quantitative values obtained by operators were correlated (r²=0.64 and r²=0.61, respectively). Systematic bias across operators as assessed using Bland-Altman plots was negligible (-0.001 and -0.29, respectively), although precision was limited (95% confidence intervals, +0.105 to -0.107 and +0.98 to -1.04, respectively). RI calculation and semi-quantitative assessment performed well for diagnosing persistent AKI (area under the receiver-operating characteristic curve, 0.84 [95% confidence interval, 0.73-0.97] and 0.87 [0.77-0.97], respectively). CONCLUSION: A brief course on renal Doppler allowed inexperienced operators to assess effectively renal perfusion with a good reliability when compared to senior operators. In addition, our results suggest the good diagnostic performance of both Doppler-based RI and semi-quantitative renal perfusion assessment in predicting short-term renal dysfunction reversibility.

Separation of heart sounds and heart murmurs by Hilbert transform envelogram.

Heart sounds and murmurs provide crucial diagnosis information for several heart diseases such as natural or prosthetic valve dysfunction and heart failure. Many pathological conditions of the cardiovascular system cause murmurs and aberrations in heart sounds. Phonocardiography provides the clinician with a complementary tool to record the heart sounds heard during auscultation. The advancement of intra-cardiac phonocardiography, combined with modern digital processing techniques, has strongly renewed researchers' interest in studying heart sounds and murmurs. This paper presents an algorithm for the detection of heart sounds (the first and second sounds, S1 and S2) and heart murmurs. The segmentation algorithm is based on the detection of the envelope of the phonocardiogram signal by the Hilbert transform technique, which is used to extract a smooth envelogram which enable one to apply the tests necessary for temporal localization of heart sounds and heart murmurs.

Analysis of the pathological severity degree of aortic stenosis (AS) and mitral stenosis (MS) using the discrete wavelet transform (DWT).

The heart is the principal organ that circulates blood. In normal conditions it produces four sounds for each cardiac cycle. However, most often only two sounds appear essential: S1 and S2. Two other sounds: S3 and S4, with lower amplitude than S1 or S2, appear occasionally in the cardiac cycle by the effect of disease or age. The presence of abnormal sounds in one cardiac cycle provide valuable information on various diseases. The aortic stenosis (AS), as being a valvular pathology, is characterized by a systolic murmur due to a narrowing of the aortic valve. The mitral stenosis (MS) is characterized by a diastolic murmur due to a reduction in the mitral valve. Early screening of these diseases is necessary; it's done by a simple technique known as: phonocardiography. Analysis of phonocardiograms signals using signal processing techniques can provide for clinicians useful information considered as a platform for significant decisions in their medical diagnosis. In this work two types of diseases were studied: aortic stenosis (AS) and mitral stenosis (MS). Each one presents six different cases. The application of the discrete wavelet transform (DWT) to analyse pathological severity of the (AS and MS was presented. Then, the calculation of various parameters was performed for each patient. This study examines the possibility of using the DWT in the analysis of pathological severity of AS and MS.

Microparticles and infectious diseases.

Membrane shedding with microvesicle (MV) release after membrane budding due to cell stimulation is a highly conserved intercellular interplay. MV can be released by micro-organisms or by host cells in the course of infectious diseases. Host MVs are divided according to cell compartment origin in microparticles (MPs) from plasma membrane and exosomes from intracellular membranes. MPs are cell fragments resulting from plasma membrane reorganization characterized by phosphatidylserine (PhtdSer) content and parental cell antigens on membrane. The role of MPs in physiology and pathophysiology is not yet well elucidated; they are a pool of bioactive molecules able to transmit a pro-inflammatory message to neighboring or target cells. The first acknowledged function of MP was the dissemination of a procoagulant potential via PhtdSer and it is now obvious than MPs bear tissue factor (TF). Such MPs have been implicated in the coagulation disorders observed during sepsis and septic shock. MPs have been implicated in the regulation of vascular tone and cardiac dysfunction in experimental sepsis. Beside a non-specific role, pathogens such as Neisseria meningitidis and Ebola Virus can specifically activate blood coagulation after TF-bearing MPs release in the bloodstream with disseminated intravascular coagulopathy and Purpura fulminans. The role of MPs in host-pathogen interactions is also fundamental in Chagas disease, where MPs could allow immune evasion by inhibiting C3 convertase. During cerebral malaria, MPs play a complex role facilitating the activation of brain endothelium that contributes to amplify vascular obstruction by parasitized erythrocytes. Phagocytosis of HIV induced MPs expressing PhtdSer by monocytes/macrophages results in cellular infection and non-inflammatory response via up-regulation of TGF-ß.

Analysis of phonocardiogram signals using wavelet transform.

Phonocardiograms (PCG) are recordings of the acoustic waves produced by the mechanical action of the heart. They generally consist of two kinds of acoustic vibrations: heart sounds and heart murmurs. Heart murmurs are often the first signs of pathological changes of the heart valves, and are usually found during auscultation in primary health care. Heart auscultation has been recognized for a long time as an important tool for the diagnosis of heart disease, although its accuracy is still insufficient to diagnose some heart diseases. It does not enable the analyst to obtain both qualitative and quantitative characteristics of the PCG signals. The efficiency of diagnosis can be improved considerably by using modern digital signal processing techniques. Therefore, these last can provide useful and valuable information on these signals. The aim of this study is to analyse PCG signals using wavelet transform. This analysis is based on an algorithm for the detection of heart sounds (the first and second sounds, S1 and S2) and heart murmurs using the PCG signal as the only source. The segmentation algorithm, which separates the components of the heart signal, is based on denoising by wavelet transform (DWT). This algorithm makes it possible to isolate individual sounds (S1 or S2) and murmurs. Thus, the analysis of various PCGs signals using wavelet transform can provide a wide range of statistical parameters related to the phonocardiogram signal.

Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside.

PURPOSE: To delineate some of the characteristics of septic vascular hypotension, to assess the most commonly cited and reported underlying mechanisms of vascular hyporesponsiveness to vasoconstrictors in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. METHODS: Source data were obtained from a PubMed search of the medical literature with the following MeSH terms: Muscle, smooth, vascular/physiopathology; hypotension/etiology; shock/physiopathology; vasodilation/physiology; shock/therapy; vasoconstrictor agents. RESULTS: Nitric oxide (NO) and peroxynitrite are crucial components implicated in vasoplegia and vascular hyporeactivity. Vascular ATP-sensitive and calcium-activated potassium channels are activated during shock and participate in hypotension. In addition, shock state is characterized by inappropriately low plasma glucocorticoid and vasopressin concentrations, a dysfunction and desensitization of alpha-receptors, and an inactivation of catecholamines by oxidation. Numerous other mechanisms have been individualized in animal models, the great majority of which involve NO: MEK1/2-ERK1/2 pathway, H(2)S, hyperglycemia, and cytoskeleton dysregulation associated with decreased actin expression. CONCLUSIONS: Many therapeutic approaches have proven their efficiency in animal models, especially therapies directed against one particular compound, but have otherwise failed when used in human shock. Nevertheless, high doses of catecholamines, vasopressin and terlipressin, hydrocortisone, activated protein C, and non-specific shock treatment have demonstrated a partial efficiency in reversing sepsis-induced hypotension.

Origin and biological significance of shed-membrane microparticles.

Microparticles (MPs) are small vesicles released from the membrane surface during eukaryotic cell activation or apoptosis. They originate from various cell types, displaying the typical surface cell proteins and cytoplasmic components of their cell origin. Their procoagulant properties are linked to phosphatidylserine exposed at their surface. Numerous reports have shown that MPs are able to mediate long-range signaling, acting on different targets from those of their own cellular origin. MPs-mediated binding to other cells occurs by integration into the membrane, by adhesion to the cell surface or by ligand-receptor interaction. Elevated levels of circulating MPs have been detected in cardiovascular and immune-mediated diseases. Despite extensive studies of the procoagulant and pro-inflammatory properties of MPs, little is known about their effect on vascular function. MPs accumulate in atherosclerotic plaques and injured vascular wall. Circulating MPs from patients with myocardial infarction induce endothelial dysfunction by impairing the endothelial nitric oxide (NO) pathway, without causing changes in endothelial NO-synthase (eNOS) expression. However, MPs from T-cells may induce endothelial dysfunction, altering gene expression of eNOS and caveolin-1. Moreover, MPs may promote the expression of pro-inflammatory proteins implicated in vascular contractility alterations. This review describes the origin of MPs and their biological role in physiological conditions and in various pathological states, with special reference to the possible linkage between their pro-inflammatory and procoagulant properties and vascular dysfunction.

Fatal allergic vasculitis associated with celecoxib.

We report on the occurrence of a rare and as yet unforseeable adverse reaction to treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective, non-steroidal, anti-inflammatory drug. A previously healthy adult suffered fatal acute multiple organ failure presumably after diffuse allergic vasculitis with diffuse necrotic purpura. Although no conclusive proof is available, such a reaction could have been triggered by at least one of two mechanisms: an allergic reaction linked to the chemical structure of celecoxib; or an interaction of the drug with synthesis of endothelial eiconasoids leading to an imbalance between vasoactive end products, resulting in widespread rise to local thrombosis.