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Lycorane is a pentacyclic core presented in alkaloids isolated from the Amaryllidaceae family of herbaceous flowering plants. Members of this class of natural products have shown to display important biological properties including analgesic, antiviral, and antiproliferative activities. This review presents the known synthetic routes toward α-, ß-, γ-, and δ-lycoranes. α-(19 routes), ß-(10 routes), γ-(38 routes), and δ-(6 routes).
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Introduction: Status asthmaticus (SA) and near-fatal asthma (NFA) are life-threatening conditions that continue to present a management challenge for physicians. Extracorporeal Membrane Oxygenation (ECMO) has been employed as a last resort in treating these patients. Case presentation: We described six patients who were admitted to the ICU for NFA and received ECMO treatment at a high-complexity institution in Cali, Colombia, between 2015 and 2019. All patients are registered in the ELSO registry. Baseline patient characteristics, arterial blood gases (ABG), ventilatory parameters, and complications were collected as specified in the ELSO registry form. Efficacy was analyzed in terms of the improvement in respiratory acidosis, the number of ventilator-free days (VFD), and a reduction in mechanical power (MP). MP, which refers to the energy associated with the mechanical forces involved in breathing and the functioning of the respiratory system, was calculated using a mathematical formula. Safety was evaluated based on the incidence of complications. After 12 hours of ECMO, we achieved a correction of respiratory acidosis, a significant decrease in all ventilatory parameters, and a reduction in MP ranging from 52.8% to 89%. There was one mortality. Among the five surviving patients, all except one, who required a tracheostomy, had a high VFD score, with a mode of 26 days, demonstrating a reduction in ventilation time. Conclusion: Further randomized controlled trials are needed to fully understand the efficacy and safety profiles of ECMO in SA/NFA. MP is being widely used to achieve safer ventilation, and although more data is required, it appears to be a promising option for evaluating the risk of developing VILI and the success of the therapy.
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Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation. IMPORTANCE: A previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.
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Infecciones Bacterianas , Pericitos , Animales , Ratones , Ovinos , Pericitos/metabolismo , Células Endoteliales , Conexina 43/metabolismo , Conexina 43/farmacología , Inflamación , Infecciones Bacterianas/metabolismoRESUMEN
Background: The present article describes three cases of patients in cardiogenic shock (CS) with previous cardiac surgery that made them initially inoperable. Perioperative support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) improved haemodynamic status and results in these high-risk patients. Case summary: Case 1 is a 57-year-old male morbidly obese with previous aortic valve replacement (AVR) who presented with chest pain and developed cardiac arrest. Cardiopulmonary resuscitation and femoral VA-ECMO were initiated. Three days later, a redo AVR was performed. Veno-arterial extracorporeal membrane oxygenation was maintained for 12 days, followed by 7 days of veno-venous ECMO for complete recovery. Case 2 features a 39-year-old male with two previous mitral valve replacements (MVRs). The first is due to papillary muscle rupture, and the second is due to endocarditis of the mitral prosthesis. He presented with CS and pulmonary oedema. Emergency surgery was performed and the patient was then placed in VA-ECMO. Weaning off was achieved 3 days after surgery. Case 3 is a 21-year-old female with a previous MVR due to rheumatic disease. She presented with CS, severe mitral prosthesis stenosis, and a pulmonary embolism. Femoral VA-ECMO was initiated, and one day later, she underwent a redo MVR operation. Extracorporeal membrane oxygenation was discontinued 4 days later. Discussion: Dysfunctional prosthetic valves leading to CS may benefit from a redo cardiac operation supported by a perioperative VA-ECMO to optimize haemodynamic status. Despite the results from risk prediction scores, this approach has the potential to reduce operative mortality in initial inoperable patients and allow a definitive redo cardiac surgery.
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AIM: To determine the incidence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in children and young people who play federated football. METHODS: Prospective study, from October 2020 to January 2021, in players aged 4 to 19 years from federated football clubs in Galicia, Spain (N = 23,845). Outbreaks and cases of SARS-CoV-2 infection were recorded. The cumulative incidence was compared with the incidence registered in Galicia in the same age range. RESULTS: The cumulative incidence was 29.8 cases per 10,000 licenses in 4 months, lower than the incidence registered in the general population for all ages and both sexes (283.7 per 10,000 inhabitants; rate ratio = 9.5). It was higher in January (40.7 per 10,000), coinciding with the population peak. More cases were registered in futsal (42.9 vs 27.5 per 10,000) and competitions with periodic screenings (127.4 vs 9.1 per 10,000). There were 2 outbreaks in 2389 teams (0.08%). CONCLUSION: The results support the safety of football practice in children and young people with prevention protocols.
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COVID-19 , Fútbol Americano , Adolescente , Niño , Femenino , Humanos , Incidencia , Masculino , Estudios Prospectivos , SARS-CoV-2RESUMEN
RATIONALE: Polydimethylsiloxane, commonly referred as silicone, is an inert liquid compound used in esthetic procedures due to its durability and thermal stability, yet the application of non-pure silicone generates risks. One of the complications is systemic embolism syndrome which is presents with fever, hypoxemia, and progression to respiratory failure, diffuse alveolar damage and alveolar hemorrhage, as well as neurological alterations in one-third of the cases. Management is strictly supportive. We present the case of acute pneumonitis with alveolar hemorrhage after silicone injection. PATIENT CONCERNS: 25-year-old transsexual man, who consulted 48âhours after liquid silicone injection in the buttocks and trochanteric area, with progressive dyspnea and chest tightness, with rapid progression to respiratory failure. DIAGNOSIS: Clinical diagnosis of silicone embolism was made. Chest x-ray and CT angiography showed diffuse alveolar infiltrates and pleural effusion without evidence of acute venous thromboembolism. Bronchoscopy plus bronchoalveolar lavage showed hemorrhagic fluid, 60% macrophages with hemosiderin in cytology and negative cultures. INTERVENTION: Sedation, relaxation, pronation, and protective ventilation were implemented until hemodynamic stabilization; as well as IV steroids and antibiotics. OUTCOMES: Clinical progress was slow towards improvement with resolution of radiological or physical abnormalities. Despite severity, the patient improved satisfactorily without late sequelae. LESSONS: Silicone injection can trigger phenomena similar to that seen in fat embolism causing inflammation and immune response activation that lead to alveolar hemorrhage, diffuse alveolar damage, and acute respiratory distress syndrome. We reported pulmonary complications related to the illegal use of injected silicone for esthetic procedures.
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Embolia/inducido químicamente , Neumonía/inducido químicamente , Síndrome de Dificultad Respiratoria/etiología , Procedimientos de Reasignación de Sexo/efectos adversos , Siliconas/efectos adversos , Adulto , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Neumonía/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Personas TransgéneroRESUMEN
INTRODUCTION: Accidental foreign body aspiration can cause severe damage to the airway and threaten the patient's life. This situation requires multidisciplinary and systematic approach from the medical and surgical team, in order to achieve complete resolution maintaining airway permeability. PRESENTATION OF CASE: This is a 49 y/o man who presented with a severe asthma attack, in whom an unsuspected foreign body in the inferior airway was diagnosed, which was possibly the result of aspiration during the initial emergency care, causing worsening of the already critical condition. DISCUSSION: We described the clinical course, radiologic and endoscopic findings, and outcome of the patient, highlighting the importance of considering the possibility of a foreign body in the airway, when there is no improvement in refractory status asthmaticus. This is particularly important in a university hospital. Moreover, the implementation of checklists when invasive procedures are performed can avoid loss of material, preventing iatrogenic aspiration events. CONCLUSION: Foreign body aspirations may remain undetected due to lack of suspicion, especially in adults, in whom they can cause chronic symptoms, or worsen chronic respiratory conditions turning them into more complex diseases. This cause must be considered in the differential diagnosis of refractory status asthmaticus.
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Lung transplantation is a life-saving alternative for patients with end-stage lung disease. The procedure itself has a high risk of bleeding. Jehovah's Witness patients refuse to accept blood products due to religious beliefs. A 48-year-old Jehovah's Witness woman presented with an 8-year history of cough, dyspnea along with progressive worsening of her functional class and quality of life. A diagnosis of autoimmune interstitial lung disease was made, for which cyclophosphamide was administered without improvement of symptoms, and the patient was accepted as a transplant candidate. Transplantation was performed without complications, nor blood products requirement, intraoperative cell salvage was performed, and pharmacological agents were used preoperatively for bleeding prevention. The patient only developed anemia after administration of immunosuppressor therapy, which was treated with erythropoietin in the outpatient setting.
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BACKGROUND: Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS. METHODS: Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after. RESULTS: Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001). CONCLUSION: Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.
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INTRODUCTION: High-flow nasal cannula oxygen therapy (HFNC) has been shown to be a useful therapy in the treatment of patients with Acute Respiratory Distress Syndrome (ARDS), but its efficacy is still unknown in patients with COVID-19. Our objective is to describe its utility as therapy for the treatment of ARDS caused by SARS-CoV-2. METHODS: A retrospective, observational study was performed at a single centre, evaluating patients with ARDS secondary to COVID-19 treated with HFNC. The main outcome was the intubation rate at day 30, which defined failure of therapy. We also analysed the role of the ROX index to predict the need for intubation. RESULTS: In the study period, 196 patients with bilateral pneumonia were admitted to our pulmonology unit, 40 of whom were treated with HFNC due to the presence of ARDS. The intubation rate at day 30 was 52.5%, and overall mortality was 22.5%. After initiating HFNC, the SpO2/FiO2 ratio was significantly better in the group that did not require intubation (113.4±6.6 vs 93.7±6.7, p=0.020), as was the ROX index (5.0±1.6 vs 4.0±1.0, p=0.018). A ROX index less than 4.94 measured 2 to 6 h after the start of therapy was associated with increased risk of intubation (HR 4.03 [95% CI 1.18 - 13.7]; p=0.026). CONCLUSION: High-flow therapy is a useful treatment in ARDS in order to avoid intubation or as a bridge therapy, and no increased mortality was observed secondary to the delay in intubation. After initiating HFNC, a ROX index below 4.94 predicts the need for intubation.
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The recent outbreaks of Chikungunya (CHIK-V) virus in endemic areas of dengue (DEN-V) could increase the risk of co-infection. CHIK infection has been considered not severe and with very unusual mortality, however DEN is associated with severe manifestations and increased mortality. Little is known about coinfection. It is possible that co-infection could generate severe cases. We present a case report of co-infection DEN-V -3 and CHIK-V in an elderly patient who developed acute renal failure, dengue shock syndrome (DSS), progresses to multiple organ failure and died. With the recent emergence of CHIK-V in Colombia, the possibility of co-infection with DEN-V should be suspected, especially in severe cases.
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Fiebre Chikungunya/epidemiología , Coinfección/epidemiología , Dengue/epidemiología , Anciano , Fiebre Chikungunya/sangre , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Coinfección/virología , Colombia/epidemiología , Dengue/sangre , Dengue/virología , Virus del Dengue/aislamiento & purificación , Humanos , Masculino , Insuficiencia Multiorgánica/virología , Carga ViralRESUMEN
The recent outbreaks of Chikungunya (CHIK-V) virus in endemic areas of dengue (DEN-V) could increase the risk of co-infection. CHIK infection has been considered not severe and with very unusual mortality, however DEN is associated with severe manifestations and increased mortality. Little is known about coinfection. It is possible that co-infection could generate severe cases. We present a case report of co-infection DEN-V -3 and CHIK-V in an elderly patient who developed acute renal failure, dengue shock syndrome (DSS), progresses to multiple organ failure and died. With the recent emergence of CHIK-V in Colombia, the possibility of co-infection with DEN-V should be suspected, especially in severe cases.
La aparición reciente del virus Chikungunya (CHIK-V) en áreas endémicas de dengue (DEN-V) podría aumentar el riesgo de co-infección. Generalmente, se considera que la infección por CHIK-V es de menor gravedad y mortalidad que DEN-V. Poco se conoce sobre la co-infección de DEN-V y CHIK-V, sin embargo, se ha planteado que la co-infección podría ser de mayor gravedad. Se presenta un caso clínico de co-infección por DENV-3 y CHIK-V en un adulto mayor quien desarrolló falla renal aguda, síndrome de choque del dengue, progresión a disfunción orgánica múltiple y muerte. Con la reciente emergencia de CHIK-V en Colombia, es necesario estar atentos ante la posibilidad de co-infección con DEN-V, en especial en casos graves.