Negative-pressure pulmonary edema after mammoplasty: a case report.

Negative-pressure pulmonary edema (NPPE) is a rare but life-threatening postoperative complication that occurs due to the acute obstruction of the upper airway. In our case report, we present a 25-year-old female patient who underwent elective mammoplasty under general anesthesia and developed NPPE 4 hours after extubation. The patient had a preoperative mallampati score of 3. After routine anesthesia induction, the patient was intubated with an endotracheal tube with a guide wire. Aspiration wasn't observed during extubation. The patient was followed in the post-anesthesia care unit (PACU) for 30 minutes with a saturation of 95% and was subsequently transferred to the service. Four hours after the operation, the patient was re-examined due to dyspnea and shortness of breath. Due to oxygen saturation of 88% and pO2of 56mmHg despite mask ventilation, the patient was admitted to the intensive care unit (ICU). A computed tomography (CT) scan revealed extensive diffuse ground-glass opacities and consolidations in both lungs. She did not respond to mask ventilation and was given non-invasive ventilation with continuous positive airway pressure (CPAP). Forced diuresis was induced with furosemide. Tachypnea resolved within 2 hours after CPAP was initiated, the patient did not require oxygen support and COVID-19 polymerase chain reaction (PCR) testing was negative. Subsequently, the patient was discharged to the clinical ward on postoperative day 1. When considering NPPE, early diagnosis and respiratory support are associated with reduced mortality and rapid recovery. Patients who develop laryngospasm during extubation must be closely monitored, and in the case of pulmonary edema, NPPE should be considered in the differential diagnosis.

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate to severe ARDS in a randomized, placebo-controlled, double-blind trial: preliminary evaluation of safety and feasibility in light of the COVID-19 pandemic.

BACKGROUND: In May 2018, the first patient was enrolled in the phase-IIb clinical trial "Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Edema in Patients with Moderate to Severe ARDS." With the onset of the COVID-19 pandemic in early 2020, the continuation and successful execution of this clinical study was in danger. Therefore, before the Data Safety Monitoring Board (DSMB) allowed proceeding with the study and enrollment of further COVID-19 ARDS patients into it, additional assessment on possible study bias was considered mandatory. METHODS: We conducted an ad hoc interim analysis of 16 patients (5 COVID-19- ARDS patients and 11 with ARDS from different causes) from the phase-IIB clinical trial. We assessed possible differences in clinical characteristics of the ARDS patients and the impact of the pandemic on study execution. RESULTS: COVID-19 patients seemed to be less sick at baseline, which also showed in higher survival rates over the 28-day observation period. Trial specific outcomes regarding pulmonary edema and ventilation parameters did not differ between the groups, nor did more general indicators of (pulmonary) sepsis like oxygenation ratio and required noradrenaline doses. CONCLUSION: The DSMB and the investigators did not find any evidence that patients suffering from ARDS due to SARS-CoV-2 may be at higher (or generally altered) risk when included in the trial, nor were there indications that those patients might influence the integrity of the study data altogether. For this reason, a continuation of the phase IIB clinical study activities can be justified. Researchers continuing clinical trials during the pandemic should always be aware that the exceptional circumstances may alter study results and therefore adaptations of the study design might be necessary.

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS-a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients. METHODS: This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days. DISCUSSION: The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion. TRIAL REGISTRATION: This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47 .

Development of an Image-Based HCS-Compatible Method for Endothelial Barrier Function Assessment.

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS.

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

A Rare Case of Partial Aortic Mechanical Valve Thrombosis With Intact Mitral Mechanical Valve Presenting With ST-Elevation Myocardial Infarction Patients.

The incidence of mechanical valve thrombosis (MVT) is around 0.4 per 100 patient-years. Mitral valve thrombosis has a higher incidence than aortic valve thrombosis with a nearly 5-fold increase. Various factors contribute to MVT. The most common cause of valve thrombosis is poor adherence/disruption of anticoagulation therapy. Low cardiac output is known to increase the risk of prosthetic valve thrombosis. Other factors such as diabetes, hypertension, and other patient comorbidities might also play a role. Decreased flow promotes hypercoagulability. Lower pressure in the left atrium (and higher velocities in the left ventricle) can partially contribute to the higher incidence of mitral MVT versus aortic MVT. The presenting symptoms usually depend on the severity of the valve thrombosis; nonobstructive valve thrombosis patients have progressive dyspnea, signs of heart failure, and systemic embolization with strokes being the most common complication. In this article, we present a case of a middle-aged woman with a history of mitral and aortic mechanical prosthesis who presented with an ST-segment elevation myocardial infarction and pulmonary edema due to mechanical aortic valve prosthesis thrombosis. She had an isolated mechanical aortic valve prosthesis thrombosis with intact mitral valve, which, to the best of our knowledge, has not yet been described. We performed a literature review by searching PubMed and Embase using the keywords "mechanical valve," "thrombosis," "aortic," and "mitral," our search did not show similar cases.

Characterization of pulmonary impairment associated with COVID-19 in patients requiring mechanical ventilation. / Caracterização do comprometimento pulmonar associado à COVID-19 em pacientes com necessidade de ventilação mecânica.

OBJECTIVE: To detect early respiratory and hemodynamic instability to characterize pulmonary impairment in patients with severe COVID-19. METHODS: We retrospectively analyzed data collected from COVID-19 patients suffering from acute respiratory failure requiring intubation and mechanical ventilation. We used transpulmonary thermodilution assessment with a PiCCO™ device. We collected demographic, respiratory, hemodynamic and echocardiographic data within the first 48 hours after admission. Descriptive statistics were used to summarize the data. RESULTS: Fifty-three patients with severe COVID-19 were admitted between March 22nd and April 7th. Twelve of them (22.6%) were monitored with a PiCCO™ device. Upon admission, the global-end diastolic volume indexed was normal (mean 738.8mL ± 209.2) and moderately increased at H48 (879mL ± 179), and the cardiac index was subnormal (2.84 ± 0.65). All patients showed extravascular lung water over 8mL/kg on admission (17.9 ± 8.9). We did not identify any argument for cardiogenic failure. CONCLUSION: In the case of severe COVID-19 pneumonia, hemodynamic and respiratory presentation is consistent with pulmonary edema without evidence of cardiogenic origin, favoring the diagnosis of acute respiratory distress syndrome.

OBJETIVO: Detectar precocemente a instabilidade respiratória e hemodinâmica para caracterizar o comprometimento pulmonar em pacientes com COVID-19 grave. MÉTODOS: Analisamos retrospectivamente os dados colhidos de pacientes com COVID-19 que apresentaram insuficiência respiratória aguda com necessidade de intubação e ventilação mecânica. Utilizamos a avaliação da termodiluição transpulmonar por meio do dispositivo PiCCO™. Foram coletados os dados demográficos, respiratórios, hemodinâmicos e ecocardiográficos dentro das primeiras 48 horas após a admissão. Para resumir os dados, utilizamos estatística descritiva. RESULTADOS: Entre 22 de março e 7 de abril de 2020, foram admitidos 23 pacientes com COVID-19 grave. Foram monitorados com o dispositivo PiCCO™ 12 (22,6%) deles. Quando da admissão, o volume diastólico final global indexado era normal (média de 738,8mL ± 209,2) e, na hora 48, encontrava-se moderadamente aumentado (879mL ± 179), enquanto o índice cardíaco se achava abaixo do normal (2,84 ± 0,65). Todos os pacientes revelaram a presença de água extravascular pulmonar acima de 8mL/kg na admissão (17,9 ± 8,9). Não identificamos qualquer evidência de origem cardiogênica. CONCLUSÃO: No caso de pneumonia grave por COVID-19, o quadro hemodinâmico e respiratório é compatível com edema pulmonar sem evidência de origem cardiogênica, o que favorece o diagnóstico de síndrome do desconforto respiratório agudo.

Severe acute respiratory syndrome coronavirus-2- or pregnancy-related cardiomyopathy, a differential to be considered in the current pandemic: a case report.

BACKGROUND: There are limited data on cardiovascular complications of coronavirus disease 2019 in pregnancy, and there are only a few case reports on coronavirus disease 2019 related cardiomyopathy in pregnancy. Differentiation between postpartum cardiomyopathy and coronavirus disease 2019 related cardiomyopathy in pregnant women who develop severe acute respiratory syndrome coronavirus-2 infection during peripartum could be challenging. Here, we present a case of possible coronavirus disease 2019 related cardiomyopathy in a pregnant patient, followed by a discussion of potential differential diagnosis. CASE PRESENTATION: In this case report, we present the case of a young pregnant Iranian woman who developed heart failure with pulmonary edema after cesarean section. She was treated because of low left ventricular ejection fraction and impression of postpartum cardiomyopathy, and her severe dyspnea improved by intravenous furosemide. On day 3, she exhibited no orthopnea or leg edema, but she was complaining of severe and dry cough. Further evaluation showed severe acute respiratory syndrome coronavirus-2 infection. CONCLUSIONS: The possibility of severe acute respiratory syndrome coronavirus-2 infection should be considered in any pregnant woman who develops cardiomyopathy and pulmonary edema.

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.