Validation of Math Model Using Porous Media for Determining Alveolar CO 2 in Ventilated Patients.

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO 2 ), area under the CO2 curve, and Pa CO2 of 0.918, 0.954, and 0.995. Determination coefficients ( R2 ) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal / Pneumocystis jirovecii pneumonia associated with diffuse alveolar hemorrhage in a renal transplant patient. Case report

La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.

Determination of the minimum alveolar concentration of sevoflurane in Holstein steers.

OBJECTIVE: To determine the minimum alveolar concentration (MAC) of sevoflurane in Holstein steers using electric stimulation. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 15 Holstein steers aged 7.3 ± 1.2 months and weighing 121 ± 25 kg. METHODS: Animals were anesthetized with sevoflurane at 8% in oxygen at 5 L minute-1 via facemask and were intubated with an orotracheal tube of a compatible size. After 15 minutes of stabilization of the initial expired concentration of sevoflurane (Fe'Sevo) at 2.6%, electrical stimulation on the thoracic limb was initiated with a sequence of 2 × 10 ms followed by 2 × 3 second electrical currents of 50 V and 50 Hz, 5 seconds apart. Following each stimulus with a negative response, the Fe'Sevo was decreased by 0.2% and a 15 minute interval was awaited before the next stimulus. The procedure was repeated until the first Fe'Sevo value with a positive motor response was obtained. The Fe'Sevo was then increased by 0.1%, followed by a new stimulus, until a negative response was obtained. The value of MAC was calculated as the arithmetic mean between the lowest Fe'Sevo associated with a negative motor response and the highest Fe'Sevo associated with a positive response. RESULTS: The mean MAC for the 15 steers was 2.0 ± 0.3%, which corresponds to 2.1 ± 0.3% at sea level. CONCLUSIONS: Based on the proposed methodology, the MAC of sevoflurane for healthy Holstein steers is 2.1 ± 0.3% at sea level. CLINICAL RELEVANCE: This Fe'Sevo value can be used to guide depth of anesthesia in steers weighing approximately 120 kg in clinical practice.

Ecografía pulmonar en la evaluación del paciente crítico / Lung ultrasound in the evaluation of critically ill patients

Introducción: La ecografía es una técnica de imagen no invasiva que permite explorar diferentes órganos de manera inmediata, constituye un instrumento de alto valor diagnóstico al alcance del profesional de la salud, y es utilizada en todas las especialidades médicas. En los últimos años, la evolución tecnológica ha permitido que los aparatos de ecografía sean más pequeños, portátiles, y con una alta resolución, tal es el caso de la ecografía clínica o ecografía a pie de cama. La ecografía del paciente crítico ha cambiado la práctica médica; específicamente la ecografía pulmonar se debe realizar en todos los pacientes con enfermedad pulmonar aguda. Objetivo: Aportar el conocimiento teórico necesario para promover el uso de la ecografía pulmonar en la evaluación del paciente crítico, y contribuir, mediante su aplicación, a la disminución del riesgo de exposición a las radiografías. Métodos: Se efectuó una revisión de la literatura médica actualizada sobre el papel de la ecografía pulmonar en la evaluación del paciente crítico, en el período de julio a diciembre de 2021. Se utilizaron los siguientes motores de búsqueda: SciELO, Medigraphic y Google Académico. Conclusiones: En el contexto actual, la ecografía pulmonar ha adquirido un papel protagónico, pues su uso facilita una evaluación frecuente y no invasiva del paciente crítico con afección pleuropulmonar. Su aplicación garantiza la disminución del riesgo de exposición a las radiografías.

Introduction: ultrasound is a non-invasive imaging technique that allows us to explore different organs immediately; it constitutes an instrument of high diagnostic value within the reach of health professionals and used in all medical specialties. In recent years, technological evolution has allowed ultrasound devices to be smaller, portable and with high resolution, such is the case of clinical ultrasound or bedside ultrasound. Bedside ultrasound in critically ill patients has changed medical practice; specifically, lung ultrasound should be performed in all patients with acute lung disease. Objective: to provide the necessary theoretical knowledge in order to promote the use of lung ultrasound in the evaluation of critically ill patients, as well as to contribute, through its application, to reduce the risk of exposure to radiographs. Methods: a review of the updated medical literature on the role of lung ultrasound in the evaluation of the critically ill patients was performed from July to December 2021. SciELO, Medigraphic and Google Scholar were the search engines used. Conclusions: lung ultrasound has acquired a leading role in the current context, since its use facilitates a non-invasive and common evaluation of the criticall ill patients with pleuropulmonary disease. Its application guarantees the reduction of the risk of exposure to X-rays.

Determination of the minimum alveolar concentration (MAC) of isoflurane and sevoflurane in Callithrix penicillatac

Background: The minimum alveolar concentration (MAC) is a measure of quantitative anesthetic potency and has become the standard index for the evaluation and comparison of volatile anesthetics, in addition to guiding dose administration. Black-tufted marmosets (Callithrix penicillata) are primates present in the clinical and surgical routine of veterinary hospitals, as well as experimental models, especially in neuroscience. Few studies have evaluated the potency of the main volatile anesthetics in this species. This study aimed to determine the MAC of isoflurane and sevoflurane in C. penicillata using the up-and-down method and to evaluate the effects of these drugs on the quality of anesthetic induction, maintenance, and recovery. Materials, Methods & Results: Twenty-four animals of undetermined age were used. All marmosets were healthy according to hematological and physical evaluation. The animals were randomly divided into 2 groups: ISOMAC and SEVOMAC. Each animal was induced to general anesthesia in an anesthetic box with oxygen (5 L/min) and sevoflurane at 7% in the SEVOMAC group or isoflurane at 5% in the ISOMAC. Upon reaching lateral decubitus, orotracheal intubation was performed. General anesthesia was maintained with isoflurane or sevoflurane diluted in oxygen (0.8 L/min) using a non-rebreathing delivery system under spontaneous ventilation. As defined in the pilot study, the first animal from ISOMAC started the maintenance of anesthesia with 2.6% isoflurane, while the first animal in SEVOMAC received 4% sevoflurane. After finishing the instrumentation to assess heart rate, respiratory rate, systolic blood pressure, pulse oximeter oxygen saturation, end-tidal carbon dioxide concentration, and rectal temperature, a 15-min wait to reach anesthetic equilibrium was allowed, and then an electrical noxious stimulation (50 mA and 50 Hz) was performed on the lateral aspect of the thigh (a faradic current of 3 consecutive single stimuli, followed by 2 continuous stimuli). The animals' responses to the electrical stimulus were observed. The presence of a positive response (gross movement of the limbs, head, or vocalization) or a negative response (absence of gross movements) determined the increase or reduction, respectively, of the inhalation anesthetic concentration by 10% in the subsequent marmoset. The quality of anesthetic induction and recovery from anesthesia was evaluated using a scale that measured the intensity of agitation, coughing, nausea, and vomiting. Physiological variables were recorded before (M0) and after (M1) applying the nociceptive stimulus. Isoflurane and sevoflurane MAC values in C. penicillata were 2.29 ± 0.10% and 3.93 ± 0.61 % respectively. Physiological parameters, quality of anesthetic induction and recovery did not differ significantly between groups. However, isoflurane caused irritation of the airway and ocular mucous membranes, more coughing episodes, and tearing at induction. There was no difference between groups for time to extubation and recovery time to regain sternal position. Discussion: Previous studies in primates found lower MAC values for both anesthetics, except for Lemur catta. Those findings may be explained by the use of different nociceptive stimuli and the MAC determination method employed, although no differences in MAC values have been described between bracketing or up-and-down methods in human primates and dogs. It is unlikely that the stimulus and technique alone are the determining factors for the high concentration of isoflurane and sevoflurane observed in the present study since MAC was high with both halogenates, indicating that dose extrapolation from other species can lead to the wrong anesthetic dosage.

Malignant alveolar neoplasm in a 10-month-old French bulldog

Background: Malignant tumors are the main cause of death or euthanasia in animals. The oral cavity ranking fourth in number of occurrences. Epidemiological studies with dogs suggest that canine cancer kills 40-50% of individuals aged over 10 years. In view of the interest of academics and professionals in the healthcare of dogs and cats, this paper reports the case of a 10-month-old bitch, which, despite being a young animal, was affected alveolar rhabdomyosarcoma of abrupt evolution. Case: A 10-month-old French Bulldog bitch, weighing 10 kg, was referred to a veterinary hospital in the city of Rio de Janeiro for care. It had a history of mouth bleeding, after chewing a solid mineral material, edema in the region of the right maxilla, and protusion of the gland of the third eyelid. As the clinical examination also revealed a fracture of the maxillary canine, anti-inflammatory and antibiotics were prescribed, to be administered by the owner once a day for 7 days. During the next clinical examination, carried out one week later, an edema was found in the right region of the mouth, which proved difficult to examine. As the patient had already eaten, an appointment was made for the following day for an intervention in the operating room, where the animal could be anesthetized for better observation of the effected region. Blood was collected for hemogram, urea, creatinine, alkaline phosphatase, ALT, and GGT, and an 8 h food fasting and a 4 h water fasting were recommended. On that date, once the dog had been taken to the operating room, was administered the pre anesthesia, in addition to anesthetic induction and manutention. Upon examining the oral cavity, several loose molars were found on the right side, in addition to a tumoral aspect of the gum; thus, it was decided to collect a small sample of the tumoral mass for histopathology. The surgical specimen was placed in a formalin solution and sent to the laboratory for histopathological processing and diagnosis. One week later, the tumor mass was larger and the edema in the right region of the mouth was much larger than on the day of the procedure. Thus, a computerized tomography was requested to further investigate the alterations that had occurred in such a short time. Due to the results of the histopathology and the CT, an immunohistochemical test was suggested which determined the cell profile and morphology and confirmed the diagnosis of alveolar rhabdomyosarcoma according to clinical suspicion. The animal remained in the veterinary hospital for a further 48 h, during which the clinical condition worsened, with the animal suffering heavy bleeding. As the patient was no longer capable of oral intake of food or water, the decision was made with the consent of the owners to induce a painless death to alleviate the suffering of the animal. However, the owners did not authorize a necropsy. Discussion: Veterinary physicians should be conscious of the treatment of serious illnesses that will not result in a benefit for the patient. They should know when to stop the treatment to not cause further pain and suffering to the animals and their owners. Many of the interventions which aim to treat severe malignant neoplasia will not promote an improvement in quality of life or significantly extend the patient's survival, and do not justify the suffering they entail. A painless death remains the best alternative in such cases.

Síndrome pulmón-riñón en pacientes con hallazgos incidentales de agentes infecciosos / Pulmonary-renal syndrome in patients with incidental findings of infectious agents

El síndrome pulmón-riñón (SPR) o síndrome reno-pulmonar es la combinación de glomerulonefritis aguda rápidamente progresiva (GNARP) y hemorragia alveolar difusa (HAD) de causa autoinmune. El SPR fue inicialmente descrito por Goodpasture en el contexto del síndrome anti-membrana basal glomerular (MBG). Actualmente, las vasculitis asociadas a ANCA (VAA) explican el 60% (rango 56­77.5%) de casos, el síndrome de Goodpasture el 15% (12.5­17.5%), y un 10% de casos se deben a otras causas. El SPR presenta un gran espectro clínico, desde la capilaritis pulmonar fulminante con HAD y falla respiratoria aguda, hasta formas más sutiles de enfermedad sólo detectables mediante lavado bronquio-alveolar (LBA). El objetivo de este estudio es presentar la primera serie peruana de SPR asociada a agentes infecciosos. Reportamos 3 casos, dos correspondieron a lupus eritematoso sistémico y uno a vasculitis asociada a poliangeítis microscópica. El primer caso se asoció a sobreinfección por C. tropicalis; el segundo caso a A. fumigatus y C. albicans; y el tercero a infestación por A. lumbricoides. Todos los casos se presentaron en mujeres, requirieron soporte ventilatorio invasivo y hemodiálisis, y dos resultaron letales. Concluimos que, el SPR es una condición clínica grave comúnmente asociada a sobreinfecciones o infestaciones, y que conlleva una elevada morbilidad y mortalidad. Puesto que no existen características clínicas específicas, resulta crucial tener un alto índice de sospecha. Las investigaciones pertinentes­pruebas inmunológicas, imagenológicas, y biopsia cutánea, renal y/o pulmonar­para precisar la etiología deben realizarse sin demora ya que el tratamiento precoz puede cambiar el pronóstico de estos pacientes(AU)

Pulmonary-renal syndrome (PRS) or reno-pulmonary syndrome is the combination of acute rapidly progressive glomerulonephritis (RPGNARP) and autoimmune diffuse alveolar hemorrhage (DAH). RPS was initially described by Goodpasture in the context of anti-glomerular basement membrane (GBM) syndrome. Currently, ANCA-associated vasculitides (AAV) explain 60% (range 56­77.5%) of cases, Goodpasture syndrome 15% (12.5­17.5%), and 10% of cases are due to other causes. PRS presents a wide clinical spectrum, from fulminant pulmonary capillaritis with ADH and acute respiratory failure, to subtler forms of disease that can only be detected by bronchoalveolar lavage (BAL). The objective of this study is to present the first Peruvian series of SPR associated with infectious agents. We report 3 cases, two corresponded to systemic lupus erythematosus and one to vasculitis associated with microscopic polyangiitis. The first case was associated with superinfection by C. tropicalis; the second case to A. fumigatus and C. albicans; and the third to infestation by A. lumbricoides. All cases occurred in women, required invasive ventilatory support and haemodialysis, and two were fatal. We conclude that SPR is a serious clinical condition commonly associated with superinfections or infestations, and that it carries high morbidity and mortality. Since there are no specific clinical features, a high index of suspicion is crucial. Relevant investigations­immunological tests, imaging tests, and skin, kidney, and/or lung biopsies­to specify the etiology should be carried out without delay, since early treatment can change the prognosis of these patients(AU)

Fisiopatología de la enfermedad COVID-19 / Pathophysiology of COVID-19 / Fisiopatologia da doença COVID-19

La enfermedad por coronavirus es una infección respiratoria causada por el virus SARS-CoV 2, el cual genera una cascada de eventos sistémicos, afectando diferentes órganos y tejidos. El entendimiento de la fisiopatología del COVID-19 es indispensable no solo al momento de brindar tratamiento a los pacientes, sino que también para comprender las causas de las complicaciones que presentan un número importante de pacientes recuperados. El objetivo de este trabajo es presentar una revisión actualizada de los efectos de la infección en diferentes órganos y sistemas principales que sea de utilidad como material de referencia para profesionales y estudiantes de la salud. Para ello se realizó una búsqueda bibliográfica en los portales PubMED, Scielo, Google Scholar, Cochrane y Springer Link, así como en las bases de repositorios científicos pre-publicación bioRxiv ("bioarchives") y medRxiv ("med-archives") y sobre un total de cerca de 200 mil artículos, se seleccionaron 100 artículos para esta revisión en base a su relevancia o sugerencias de parte de profesionales especializados.

Coronavirus disease is a respiratory infection caused by the SARS-CoV-2 virus, which causes a cascade of systemic events, affecting various organs and tissues. Understanding the pathophysiology of COVID-19 is essential to treat patients and understand the causes of the complications in a significant number of recovered patients. This article presents a review of the effects of infection on various organs and systems that will be useful as reference material for healthcare professionals and medical students. To this end, a literature search was conducted in PubMED, Scielo, Google Scholar, Cochrane, and Springer Link portals, as well as in the pre-publication scientific repositories bioRxiv ("bioarchives") and medRxiv ("med-archives") databases. From about 200,000 papers, 100 articles were selected for this review based on their relevance or suggestions from experts in the field.

A doença coronavírus é uma infecção respiratória causada pelo vírus SARS-CoV-2, que gera uma cascata de eventos sistêmicos, afetando diferentes órgãos e tecidos. Compreender a fisiopatologia da COVID-19 é essencial não apenas no tratamento de pacientes, mas também para compreender as causas das complicações que um número significativo de pacientes recuperados apresenta. O objetivo deste trabalho é apresentar uma revisão atualizada dos efeitos da infecção em diferentes órgãos e principais sistemas que seja útil como material de referência para profissionais de saúde e estudantes. Para isso, foi realizada uma pesquisa bibliográfica nos portais PubMED, Scielo, Google Scholar, Cochrane e Springer Link, bem como nos repositórios científicos de pré-publicação bioRxiv ("bioarquivos") e medRxiv ("arquivos med"). Num total de cerca de 200 mil artigos, 100 artigos foram selecionados para esta revisão por sua relevância ou sugestões de profissionais especializados.

Hemorragia alveolar pulmonar como presentación poco frecuente de infección por Leptospira spp: una enfermedad ocupacional del personal militar en zonas tropicales / Pulmonary alveolar hemorrhage as an unusual presentation of Leptospira spp: an occupational-disease of military personnel in tropical zones

Resumen La leptospirosis es una de las zoonosis endémicas más importantes en el mundo con un aumento de la incidencia en los últimos años. En el personal militar podría ser catalogada como una enfermedad ocupacional dado sus actividades específicas en áreas rurales. Su presentación clínica es variable siendo en la mayoría de los casos una enfermedad febril autolimitada. De acuerdo con diversos factores dependientes del patógeno y del hospedero pueden presentarse manifestaciones severas de la enfermedad dentro de la cual destaca el compromiso pulmonar con una alta tasa de mortalidad. Existe evidencia del uso de esteroide sistémico como parte del tratamiento de esta complicación. Presentamos el caso de un paciente joven, militar, que debuta con síndrome de hemorragia alveolar difusa secundario a leptospirosis y presenta una excelente respuesta al tratamiento con altas dosis de metilprednisolona, con una discusión del proceso diagnóstico y aspectos fisiopatológicos de esta condición.

Leptospirosis is one of the most important endemic zoonoses in the world with an increase in incidence in recent years. In military personnel it could be classified as an occupational disease given their specific activities in rural areas. Its clinical presentation is variable being in most cases a self-limited febrile disease. According to various factors dependent on the pathogen and the host, severe manifestations of the disease may occur within which the pulmonary involvement with a high mortality rate stands out. There is evidence of systemic steroid use as part of the treatment of this complication. We present a case of a young, military patient who debuts with diffuse alveolar hemorrhage syndrome secondary to leptospirosis and presents an excellent response to treatment with high doses of methylprednisolone, with a discussion of the diagnostic process and pathophysiological aspects of this condition.

Airway and Alveoli Organoids as Valuable Research Tools in COVID-19.

The coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, affects tissues from different body systems but mostly the respiratory system, and the damage evoked in the lungs may occasionally result in severe respiratory complications and eventually lead to death. Studies of human respiratory infections have been limited by the scarcity of functional models that mimic in vivo physiology and pathophysiology. In the last decades, organoid models have emerged as potential research tools due to the possibility of reproducing in vivo tissue in culture. Despite being studied for over one year, there is still no effective treatment against COVID-19, and investigations using pulmonary tissue and possible therapeutics are still very limited. Thus, human lung organoids can provide robust support to simulate SARS-CoV-2 infection and replication and aid in a better understanding of their effects in human tissue. The present review describes methodological aspects of different protocols to develop airway and alveoli organoids, which have a promising perspective to further investigate COVID-19.

Loss of MT1-MMP in Alveolar Epithelial Cells Exacerbates Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal age-related lung disease whose pathogenesis involves an aberrant response of alveolar epithelial cells (AEC). Activated epithelial cells secrete mediators that participate in the activation of fibroblasts and the excessive deposition of extracellular matrix proteins. Previous studies indicate that matrix metalloproteinase 14 (MMP14) is increased in the lung epithelium in patients with IPF, however, the role of this membrane-type matrix metalloproteinase has not been elucidated. In this study, the role of Mmp14 was explored in experimental lung fibrosis induced with bleomycin in a conditional mouse model of lung epithelial MMP14-specific genetic deletion. Our results show that epithelial Mmp14 deficiency in mice increases the severity and extension of fibrotic injury and affects the resolution of the lesions. Gain-and loss-of-function experiments with human epithelial cell line A549 demonstrated that cells with a deficiency of MMP14 exhibited increased senescence-associated markers. Moreover, conditioned medium from these cells increased fibroblast expression of fibrotic molecules. These findings suggest a new anti-fibrotic mechanism of MMP14 associated with anti-senescent activity, and consequently, its absence results in impaired lung repair. Increased MMP14 in IPF may represent an anti-fibrotic mechanism that is overwhelmed by the strong profibrotic microenvironment that characterizes this disease.

Tracking the time course of pathological patterns of lung injury in severe COVID-19.

BACKGROUND: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. METHODS: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. RESULTS: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. CONCLUSION: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.

Transbronchial biopsies' histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure.

We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient's deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies.

Anatomopathological Aspects and Clinical Correlation of COVID-19: A Systematic Review.

OBJECTIVE: The objective of this systematic review was to analyze the main morphofunctional changes in the involvement of multiple organs in patients infected with SARS-CoV-2, correlating anatomopathological findings with the clinical picture. METHODS: The present study selected articles through electronic search of indexed journals in the PubMed and SciVerse Scopus databases, from December 2019 to May 2020, using the keywords "autopsy," "pathogenicity," and "COVID-19." Two hundred nine articles were identified, and the full texts of 18 articles were reviewed, 5 of them being selected for this review. RESULTS: The ACE2 receptor plays a role in introducing viral material into the cell, having high expression in type II alveoli. Histopathological analyzes of the lungs of patients with COVID-19 show that SARS-CoV-2 produces, in this organ, in addition to an inflammatory process, a diffuse alveolar damage (DAD), which can cause acute respiratory distress syndrome (ARDS). Macroscopically, the lungs become heavier, firmer, and redder. The clinical features of these patients are variable; the most common are respiratory symptoms associated with fever, myalgia, or fatigue. CONCLUSION: The observations points to the consensus that the lungs are the main targets of COVID-19, with morphological and functional changes of interest, including important sequels, and presenting diffuse alveolar damage as a substrate for an unfavorable outcome with ARDS. Changes in micro and macroscopic levels corroborate to the clinical progression of the disease and that these alterations are not specific, which ratify, in addition to the anatomopathological examination, a need to use the association of clinical and epidemiological data for diagnostic confirmation.

Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers.

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.

The architecture of alveolar capillaries in the lungs of bactrian camels (Camelus bactrianus) / Arquitectura de los capilares alveolares de pulmones de camellos bactrianos (Camelus bactrianus)

SUMMARY: The Bactrian camel, which is native to China and Mongolia, is large in size and is an even-toed ungulate species. The double humps on the Bactrian camel back differentiate it from the dromedary camel, which has a single hump. This species has adapted to unsuitable conditions (lack of food and water) in the Gobi Desert and is advanced in unique anatomical and physiological characteristics during a prolonged evolution period. Several studies have been conducted on the anatomical features of the Bactrian camel, but none have given attention to the alveolar capillaries of the Bactrian camel lung. Therefore, the current study aims to explore the architecture of the alveolar capillary in the Bactrian camel lung and further explain the mechanism of blood flow in its lung. The current study extracted and examined the architecture of the alveolar capillary in the lung of the Bactrian camel (Camelus bactrianus) and further explained the mechanism of blood flow by performing lung casting and replica scanning electron microscopy methods. The reports showed that the resources of the alveolar-capillary originated from the capillaries of the subpleural space or interlobular septulum, sometimes originating from the precapillary arterioles or directly from the terminal arterioles. The alveolar capillaries anastomosed and formed a single layer of dense, basket-like network surrounding the alveolus. The mash diameter of the alveolar-capillary network was larger than that of the capillary, and the appearance of the mash was oval and elliptical. Many of the collapsed alveolar-capillary networks were found in the alveolar microvascular architecture in the lung of the Bactrian camel. The study found that, due to many collapsed alveoli in the Bactrian camel lung, the disproportional pressure between the pulmonary alveoli induced less imbalance of blood flow in the alveolar capillary, which affected the gas exchange efficiency. Therefore, the function of the anastomosing capillary branch was likely to regulate the blood flow between the alveolar-capillary network.

RESUMEN: El camello bactriano, es originario de China y Mongolia, es de gran tamaño y es una especie de ungulado de dedos pares. Las dobles jorobas del lomo del camello bactriano lo diferencian del dromedario, que tiene una sola joroba. Esta especie se ha adaptado a condiciones inadecuadas (falta de alimento y agua) en el desierto de Gobi y ha avanzado en características anatómicas y fisiológicas únicas durante un período de evolución prolongado. Se han realizado varios estudios sobre las características anatómicas del camello bactriano, pero ninguno ha prestado atención a los capilares alveolares del pulmón de este animal. Por lo tanto, el presente estudio tuvo como objetivo principal explorar la arquitectura del capilar alveolar en el pulmón del camello bactriano y explicar el mecanismo del flujo sanguíneo. A partir de nuestro trabajo se examinó la arquitectura del capilar alveolar en el pulmón del camello bactriano (Camelus bactrianus) mediante la realización de métodos de microscopía electrónica de barrido y escaneo pulmonar. Los informes mostraron que los recursos del alvéolo-capilar se originaban en los capilares del espacio subpleural o del tabique interlobulillar y a veces se originaban en las arteriolas precapilares o directamente en las arteriolas terminales. Los capilares alveolares se anastomosaban y formaban una densa red de capa única en forma de cesta que rodeaba el alvéolo. El diámetro del macerado de la red alveolar-capilar era mayor que el del capilar y el aspecto del macerado era ovalado y elíptico. Muchas de las redes alvéolo-capilares colapsadas se encontraron en la arquitectura microvascular alveolar en el pulmón del camello bactriano. El estudio encontró que, muchos alvéolos colapsados en el pulmón del camello bactriano, la presión desproporcionada entre los alvéolos pulmonares inducía un menor desequilibrio del flujo sanguíneo en el capilar alveolar, lo que afectaba la eficiencia del intercambio de gases. Por lo tanto, la función de la rama capilar anastomosante probablemente regularía el flujo sanguíneo entre la red alveolar-capilar.

SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells.

SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in acute lung inflammatory edema; the renin-angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.

Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis.

It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (n = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia (n = 10) or Control specimens (n = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117+ cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.