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High-altitude pulmonary edema (HAPE) is the main cause of nontraumatic death at high altitude. HAPE development is not only related to the mode and speed of ascent and the maximum altitude reached, but also individual susceptibility plays an important role. In susceptible individuals, hypoxic pulmonary vasoconstriction leads to exaggerated elevated pulmonary arterial pressures and capillary leakage in the lungs. Thus, this review provides an overview of studies investigating the genetic background in HAPE susceptibles by focusing on specific variants, entire genes, genome-wide signatures, or family studies.

Swimming-induced pulmonary edema (SIPE) is a rare form of non-cardiogenic pulmonary edema occurring in swimmers. It is important to consider the diagnosis of SIPE and differentiate it from aspiration pneumonitis in patients presenting with respiratory distress after swimming. We report a case of military recruit who developed SIPE. This is the first reported case of SIPE from India. Owing to the paucity of reported cases, the treatment of this entity in the literature is anecdotal, and we present successful management of SIPE with non-invasive ventilation and diuretics. A review of literature is made to understand the diagnosis, pathophysiology, and management of SIPE.

Introducción El síndrome de dificultad respiratoria agudo (SDRA) es actualmente el principal diagnóstico en las unidades de cuidado intensivo (UCI), el cual está relacionado con la pandemia del SARS-CoV-2. Este síndrome aumenta la estancia, los costos hospitalarios y tiene alta mortalidad. La radiografía de tórax es un método imprescindible en estos pacientes para el diagnóstico y seguimiento clínico, por ser económico y de uso rutinario en UCI. El puntaje RALE (evaluación radiográfica del edema pulmonar) permite la estimación de la extensión y densidad de las opacidades alveolares en la radiografía torácica y se ha asociado con diferentes desenlaces clínicos como la oxigenación, mortalidad a los 28 días, días libres de ventilador, estancia hospitalaria y severidad del SDRA. El objetivo de este trabajo es establecer la asociación del RALE con desenlaces clínicos de los pacientes con SDRA de nuestra institución. Materiales y métodos Estudio de cohorte ambispectiva, monocéntrico. Se incluyeron adultos mayores de 18 años con diagnóstico de SDRA hospitalizados en las UCI del Hospital Santa Clara, de Bogotá, Colombia, de enero a diciembre de 2020. Resultados El estudio incluyó 100 pacientes, el 93% con diagnóstico de SARS-CoV-2; se encontró asociación entre el RALE del primer día y la oxigenación del primer día de ingreso, pero no se halló relación estadísticamente significativa del RALE con los otros desenlaces. Conclusión El puntaje RALE no se asoció con los desenlaces clínicos relevantes en los pacientes con SDRA. Esto se puede explicar por los diferentes mecanismos de hipoxemia de estos pacientes. Se sugiere realizar otros estudios para confirmar estos hallazgos.

Residual congestion detected using handheld ultrasound may be associated with increased risk of readmission and death after hospitalization for acute decompensated heart failure (ADHF). However, effective application necessitates routine use by nonexperts delivering clinical care.The objective of this study was to determine the ability of heart failure (HF) nurses to deliver a predischarge lung and inferior vena cava (IVC) assessment (LUICA) to predict 90-day outcomes.In this multisite, prospective, observational study, HF nurses scanned 240 patients with ADHF (median age: 77 years; 56% men) using a 9-zone LUICA protocol. Obtained images were reviewed by independent nurses who were blinded to clinical characteristics and outcomes. Based on a B-line cut-off of 10, patients were dichotomized as congested (n = 115) or not congested (n = 125).Congested patients were more likely to have previous cardiac operations, long-standing HF (6 months), and renal impairment. At 90 days, HF readmission or mortality occurred in 42 congested patients (37%) compared with 18 noncongested patients (14%). Pulmonary congestion increased at 30-day (OR: 3.86; 95% CI: 1.65-8.99; P 0.01) and 90-day (OR: 3.42; 95% CI: 1.82-6.4; P 0.01) HF readmission or mortality risk and 90-day mortality (OR: 5.18; 95% CI: 1.44-18.69; P 0.01). Pulmonary congestion increased the 90-day odds of HF readmission and/or death by 3.3- to 4.2-fold (P 0.01), independent of demographics, HF characteristics, comorbidities, and event risk score. Over 90 days, days alive out of hospital were fewer (78.3 ± 21.4 days vs 85.5 ± 12.4 days; P 0.01) in congested patients.LUICA can be a powerful tool for detection of predischarge residual congestion. HF nurses can obtain images and provide diagnostic reports that are predictive of ADHF outcomes.

Extra-corporeal membrane oxygenation (ECMO) can be used to treat patients with severe cardiac and/or pulmonary failure. ECMO has been used during pregnancy, at the time of delivery and in the post-partum period with favorable maternal and fetal outcomes.1 In our case, ECMO was initiated intra-operatively during hemorrhagic shock associated with a caesarean delivery, and accompanied by severe pulmonary edema, mitral regurgitation, hypoxia, and cardiac arrest. Research has shown that there is an optimal timing for ECMO initiation. Favorable outcomes are often seen with early initiation.2 This is especially true in pregnancy, when both maternal and fetal health are at stake.2

The Radiographic Assessment of Lung Edema (RALE) score has been used to estimate the extent of pulmonary damage in patients with acute respiratory distress syndrome and might be useful in patients with COVID-19.To examine factors associated with the need for mechanical ventilation in hospitalized patients with a clinical diagnosis of COVID-19, and to estimate the predictive value of the RALE score.In a series of patients admitted between April 14 and August 28, 2020, with a clinical diagnosis of COVID-19, we assessed lung involvement on the chest radiograph using the RALE score. We examined factors associated with the need for mechanical ventilation in bivariate and multivariate analysis. The area under the receiver operating curve (AUC) indicated the predictive value of the RALE score for need for mechanical ventilation.Among 189 patients, 90 (48%) were judged to need mechanical ventilation, although only 60 were placed on a ventilator. The factors associated with the need for mechanical ventilation were a RALE score6 points, age50 years, and presence of chronic kidney disease. The AUC for the RALE score was 60.9% (95% CI 52.9-68.9), indicating it was an acceptable predictor of needing mechanical ventilation.A score for extent of pulmonary oedema on the plain chest radiograph was a useful predictor of the need for mechanical ventilation of hospitalized patients with COVID-19.

Dyspnea is a common Emergency Department (ED) complaint of which acute pulmonary edema (APE) is a potentially life-threatening etiology. Remote Dielectric Sensing (ReDS™) is a novel, non-invasive, radar based, rapid, point of care vest testing system used to objectively quantify lung fluid content and may be useful in the early diagnosis of APE.To determine the accuracy of ReDS to detect pathologic lung fluid in ED undifferentiated dyspneic patients.We performed a prospective convenience sample observation pilot study enrolling adult ED patients with a chief complaint of "shortness of breath." After informed consent, patients were fitted with the ReDS vest and a reading, blinded to the care team, was recorded. A gold standard diagnosis of pulmonary edema, determined by 2 physicians performing a chart review and blinded to ReDs data, was compared to the ReDS reading.Overall, 123 patients were included; 59% (n = 73) were male, mean (SD) age 57.2 (±12) years, 46.3% (n = 57) Hispanic, 34.1%(n = 42) African American, 13.0% (n = 16) Caucasian and 5.7% (n = 7) Asian. The gold standard diagnosis showed pulmonary edema in 38 (30.9%) patients, of which 30 were detected by ReDS. At an optimal cutoff (≥ 37%), ReDS had a Sn of 79.5% (CI 63.5% - 90.5%), Sp of 72.6% (CI 61.8% - 81.8%), a PPV of 57.4% and a NPV of 88.4%.ReDS is moderately sensitive and specific with an accuracy of 74.8% for pulmonary edema.

The authors hypothesized that quantitative computed tomography (QCT) imaging would reveal subclinical increases in lung congestion in patients with heart failure and preserved ejection fraction (HFpEF) and that this would be related to pulmonary vascular hemodynamic abnormalities.Gross evidence of lung congestion on physical examination, laboratory tests, and radiography is typically absent among compensated ambulatory patients with HFpEF. However, pulmonary gas transfer abnormalities are commonly observed and associated with poor outcomes.Patients referred for invasive hemodynamic exercise testing who had undergone chest computed tomography imaging within 1 month were identified (N = 137). A novel artificial intelligence QCT algorithm was used to measure pulmonary fluid content.Compared with control subjects with noncardiac dyspnea, patients with HFpEF displayed increased mean lung density (-758 HU [-793, -709 HU] vs -787 HU [-828, -747 HU]; P = 0.002) and a higher ratio of extravascular lung water to total lung volume (EVLWV/TLV) (1.25 [0.80, 1.76] vs 0.66 [0.01, 1.03]; P 0.0001) by QCT imaging, indicating greater lung congestion. EVLWV/TLV was directly correlated with pulmonary vascular pressures at rest, with stronger correlations observed during exercise. Patients with increasing tertiles of EVLWV/TLV demonstrated higher mean pulmonary artery pressures at rest (34 ± 11 mm Hg vs 39 ± 14 mm Hg vs 45 ± 17 mm Hg; P = 0.0003) and during exercise (55 ± 17 mm Hg vs 59 ± 17 mm Hg vs 69 ± 22 mm Hg; P = 0.0003).QCT imaging identifies subclinical lung congestion in HFpEF that is not clinically apparent but is related to abnormalities in pulmonary vascular hemodynamics. These data provide new insight into the long-term effects of altered hemodynamics on pulmonary structure and function in HFpEF.

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

A one-year-old, French Bulldog was referred for the management of a severe form of pulmonary valve stenosis (PS) complicated by right-sided congestive heart failure. Echocardiography showed severe valvular PS with right ventricular concentric hypertrophy, dilatation and severe right atrial enlargement. A pulmonary balloon valvuloplasty (PBV) was performed with a balloon-to-pulmonary annulus ratio of 1.36. Echocardiography immediately after PBV showed a significant reduction in right atrial and ventricular size, improved opening and mobility of the pulmonary valve leaflets, and a 75% reduction in the pulmonary pressure gradient from 158 mmHg pre-operative to 40 mmHg post-operative. The dog recovered well from anesthesia, but two hours later suddenly showed severe respiratory distress. Focus cardiac ultrasound showed increased left cardiac size with echocardiographic signs of high left ventricular filling pressure. Bedside lung ultrasound showed diffuse numerous-to-confluent B lines, compatible with severe alveolar-interstitial syndrome. The dog was treated with furosemide, helmet continuous positive airway pressure and then mechanical ventilation but without success. At post-mortem evaluation, histological examination of the lung showed diffuse, severe broncho-alveolar edema with mixed leukocyte, fibrin and red blood cell infiltrate. Moreover, severe congestion and multifocal alveolar hemorrhages were evident. All findings were compatible with fatal acute lung injury after PBV secondary to pulmonary reperfusion-ischemia injury and increased pulmonary capillary hydrostatic pressure. Based on the present case, acute lung injury should be considered as a rare but serious complication of PBV.

Pulmonic stenosis is a frequent congenital heart disease in dogs, and the treatment of choice is balloon valvuloplasty which is usually safe and successful. The authors describe for the first time a severe complication after balloon valvuloplasty in a five-month-old dog. After effective treatment, with a considerable drop in right ventricular pressures, the dog developed hypoxemia and dyspnea due to pulmonary edema. The dog underwent intensive care and symptoms improved after a few hours of oxygen therapy, continuous positive airway pressure, and furosemide. Although this event is rare, it could have a large impact on patient survival and should be considered in the treatment of severe pulmonary valve stenosis in the future.

Purpose In the last three decades, Synchrotron Microbeam Radiation Therapy (S-MRT) has been shown to achieve both good tumour control and normal tissue sparing in a range of pre-clinical animal models. However, the use of S-MRT for the treatment of lung tumours has not yet been investigated. This study is the first to evaluate the therapeutic efficacy of S-MRT for the treatment of lung carcinoma, using a new syngeneic and orthotopic mouse model. Methods and materials Lewis Lung carcinoma-bearing mice were irradiated with two cross-fired arrays of S-MRT or Synchrotron Broad-Beam (S-BB) radiotherapy. S-MRT consisted of 17 microbeams with a width of 50 µm and centre-to-centre spacing of 400 µm. Each microbeam delivered a peak entrance dose of 400 Gy while S-BB delivered a homogeneous entrance dose of 5.16 Gy (corresponding to the S-MRT valley dose). Results Both treatments prolonged the survival of mice relative to the untreated controls (CTR). However, mice in the S-MRT group developed severe pulmonary oedema around the irradiated carcinomas and did not have improved survival relative to the S-BB group. Subsequent post-mortem examination of tumour size revealed that the mice in the S-MRT group had notably smaller tumour volume compared to the S-BB group, despite the presence of oedema. Mice that were sham-implanted did not display any decline in health following S-MRT, experiencing only mild and transient oedema between 4 days and 3 months post-irradiation which disappeared after 4 months. Finally, a parallel study investigating the lungs of healthy mice showed the complete absence of radiation-induced pulmonary fibrosis 6 months after S-MRT. Conclusions S-MRT is a promising tool for the treatment of lung carcinoma, reducing tumour size compared to mice treated with S-BB and sparing healthy lungs from pulmonary fibrosis. Future experiments should focus on optimising S-MRT parameters to minimise pulmonary oedema and maximise the therapeutic ratio.

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs

Background Despite increasing awareness of swimming-induced pulmonary edema (SIPE), large population-based studies are lacking and the incidence is unknown. Research question What is the incidence of SIPE in a mixed group of competitive and recreational swimmers during a large open-water swimming event? Methods In four consecutive years (2016-2019), a prospective cohort study was conducted during Sweden's largest open-water swimming event, Vansbrosimningen. All swimmers seeking medical care with acute respiratory symptoms were eligible for the study. SIPE diagnosis was based on clinical findings in 2016 and 2017 and pulmonary edema assessed by lung ultrasound in 2018 and 2019. Data on patient characteristics, clinical findings, and information about the race were collected. Results Based on 47,573 consecutive swimming distances, 322 patients with acute respiratory symptoms (0.68%; CI, 0.61%-0.75%) were treated at the mobile medical unit. Of these, 211 patients (0.44%; CI, 0.39%-0.51%) received a diagnosis of SIPE. The annual incidence of SIPE was 0.34%, 0.47%, 0.41%, and 0.57%, respectively, from 2016 through 2019. Most patients receiving a diagnosis of SIPE were women (90%), despite about equal percentages of men and women participating (47% men and 53% women). The incidence of SIPE overall was 0.75% in women and 0.09% in men. The incidence increased with age, from 0.08% in the youngest age group (18-30 years) to 1.1% in the oldest age group (≥ 61 years). Based on multiple logistic regression analysis, the adjusted odds for SIPE occurring was 8.59 times higher for women compared with men and 12.74 times higher for the oldest age group compared with the youngest age group. Interpretation The incidence of SIPE over 4 years during a large open-water swimming event in Sweden was 0.44%. The incidence was higher in women than in men and increased with age.

Background The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood. Research Question What is the incidence and clinical outcome of RV involvement in TTS? Study Design and Methods This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias. Results The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P Interpretation RV involvement defines a high-risk cohort of patients with TTS. Clinical Trial Registration ClinicalTrials.gov ; No.: NCT04361994 ; URL: www.clinicaltrials.gov .

Background Nowadays, there is no approved targeted agent for lung injury induced by sepsis. S1PR2 is confirmed to be a promising diagnosis and treatment target. JTE-013 as S1PR2 antagonists may be an agent of great potential. In this research, we sought to determine the functional role of JTE-013 in lung injury induced by sepsis. Materials and methods Seventy-two rats were assigned into normal group, sepsis model group and JTE-013 group. The animal model of lung injury induced by sepsis was constructed by cecal ligation and puncture. The human pulmonary microvascular endothelial cells (HPMECs) were divided into control, LPS and LPS + JTE-013 group. HPMECs induced by LPS served as the cell model of lung injury induced by sepsis. HE staining assay was performed for assessment of the pathological condition and Evans blue was applied for assessment of pulmonary tissue permeability. Wet/dry ratio was measured as indicators of pulmonary edema degree and neutrophil count was measured as indicators of infection status. The levels of inflammatory factors were detected by corresponding kits, cell survival by CCK-8 assay and protein expression level by western blot. Results S1PR2 was highly expressed in vivo model of lung injury induced by sepsis. It was observed that JTE-013 as antagonist of S1PR2 alleviated the lung tissue injury, endothelial dysfunction and pulmonary edema induced by sepsis. In addition, JTE-013 reduced neutrophil count and levels of inflammatory factors. Moreover, results confirmed that JTE-013 enhanced cell viability and mitigated inflammatory response in cell model of sepsis. Conclusions Overall, JTE-013 as an antagonist of S1PR2 could relieve inflammatory injury and endothelial dysfunction induced by sepsis in vivo and vitro, resulting in attenuation of lung injury. These findings elucidated that JTE-013 may be a promising targeted agent for lung injury induced by sepsis.

Introduction Prior research identified possible interstitial pulmonary fluid, concerning for early high altitude pulmonary edema (HAPE), in a large percentage of trekkers above 3000 m using a comprehensive 28-view pulmonary ultrasound protocol. These trekkers had no clinical symptoms of HAPE despite these ultrasound findings. The more common 4-view lung ultrasound protocol (LUP) is accurate in rapidly detecting interstitial edema during resource-rich care. The objective of this study was to evaluate whether the 4-view LUP detects interstitial fluid in trekkers ascending to Everest Base Camp. Methods Serial 4-view LUP was performed on 15 healthy trekkers during a 9-d ascent from Kathmandu to Everest Base Camp. Ascent protocols complied with Wilderness Medical Society guidelines for staged ascent. A 4-view LUP was performed in accordance with the published 2012 international consensus protocols on lung ultrasound. Symptom assessment and 4-view LUP were obtained at 6 waypoints along the staged ascent. A 4-view LUP was positive for interstitial edema if ≥3 B-lines were detected in 2 ultrasound windows. Results A single participant had evidence of interstitial lung fluid at 5380 m as defined by the 4-view LUP. There was no evidence of interstitial fluid in any participant below 5380 m. One participant was evacuated for acute altitude sickness at 4000 m but showed no preceding sonographic evidence of interstitial fluid. Conclusions In this small study, sonographic detection of interstitial fluid, suggestive of early HAPE, was not identified by the 4-view LUP protocol.

Several important complications of pneumonectomy are discussed in a case-based format. Topics include chylothorax, cardiac herniation, postpneumonectomy syndrome, postpneumonectomy pulmonary edema, bronchopleural fistula, and empyema.

Background We aimed to review records from 429 patients with high altitude pulmonary edema (HAPE) to identify some of the salient characteristics associated with this condition. Materials and Methods General information and clinical symptoms, along with laboratory test results from HAPE patients were collected and analyzed. Blood assay results and imaging at admission were compared with those at discharge. Results from routine blood assays were compared among three subgroups of these patients that were generated based upon the duration of their hypoxia exposure. Results Of these 429 HAPE patients, 9.32% also showed high altitude cerebral edema (HACE). White blood cell and neutrophil counts, as well as levels of alanine aminotransferase and aspartate aminotransferase, uric acid, lactic dehydrogenase and creatine kinase were all increased in HAPE patients, with further increases observed in those with HAPE combined with HACE. Levels of white blood cells, neutrophils, lymphocytes, and hemoglobin concentrations in HAPE patients at admission were significantly higher than that obtained at discharge. White blood cell and neutrophil counts were lower in patients who developed HAPE after a duration of 7 days of high altitude exposure as compared with those who developed the condition within 1 or 3 days. Conclusions A combination of HAPE and HACE was present in 9.32% of the patients with HAPE. HAPE was more prevalent in males. Hepatocytes and the myocardium were likely sites of damage in patients with HAPE, with more severe damage observed in the patients with HAPE/HACE. White blood cell and neutrophil counts were significantly higher than normal ranges and these levels were negatively correlated with the duration of hypoxia exposure.

Cardiogenic unilateral pulmonary edema (UPE) is an uncommon clinical entity and it represents just 2% of cardiogenic pulmonary edema with inclination for the right upper lobe and it is most commonly associated with severe mitral regurgitation. In our review, the literature does not include any UPE cases that are associated with severe aortic regurgitation (AR). Herein, we present a case with UPE, that includes a patient diagnosed with infective endocarditis who presented with shortness of breath. Initial chest imaging revealed UPE. Severe acute AR was diagnosed clinically and confirmed by echocardiogram, caused by vegetations on the non-coronary cusp of the aortic valve. The patient was transferred for emergent surgical intervention. This case underscores the importance of emergently evaluating valvular pathology to reduce the mortality rate that is associated with this condition.

Influenza A virus (IAV) infection alters lung epithelial cell metabolism in vitro by promoting a glycolytic shift. We hypothesized that this shift benefits the virus rather than the host and that inhibition of glycolysis would improve infection outcomes. A/WSN/33 IAV-inoculated C57BL/6 mice were treated daily from 1 day post-inoculation (d.p.i.) with 2-deoxy- d -glucose (2-DG) to inhibit glycolysis and with the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) to promote flux through the TCA cycle. To block OXPHOS, mice were treated every other day from 1 d.p.i. with the Complex I inhibitor rotenone (ROT). 2-DG significantly decreased nocturnal activity, reduced respiratory exchange ratios, worsened hypoxemia, exacerbated lung dysfunction, and increased humoral inflammation at 6 d.p.i. DCA and ROT treatment normalized oxygenation and airway resistance and attenuated IAV-induced pulmonary edema, histopathology, and nitrotyrosine formation. None of the treatments altered viral replication. These data suggest that a shift to glycolysis is host-protective in influenza.

Describe a series of patients who developed naloxone-associated pulmonary edema after recreational opioid use.Single center retrospective case series of patients who developed pulmonary edema following the prehospital administration of naloxone.Academic, urban safety-net hospital.Adults with recreational opioid overdose who developed naloxone-associated pulmonary edema, defined as the acute onset of respiratory distress, hypoxemia, and radiographic pulmonary edema after naloxone administration for opioid intoxication, provided that gas exchange and chest imaging rapidly improved and pulmonary aspiration of gastric contents was not clinically suspected.Ten adults (median age 23 years, 90% male) met our case definition for naloxone-associated pulmonary edema. Implicated opioids were heroin in 8 patients and methadone and oxycodone in 1 patient each. The median total dose of naloxone was 4.25 mg (interquartile range [IQR] 3.3-9.8) prior to the onset of clinically-apparent pulmonary edema. Seven patients received invasive mechanical ventilation for a median of two days (IQR 0.8-5), one of whom received veno-venous extracorporeal membrane oxygenation support, and all survived to hospital discharge.Severe acute pulmonary edema may follow naloxone administration after recreational opioid overdose. Acute care clinicians should be aware of this potentially life-threatening adverse effect of naloxone.

Sympathetic crashing acute pulmonary edema (SCAPE) describes the most severe presentation of acute heart failure (AHF). Immediate intervention is required to prevent hemodynamic decompensation and endotracheal intubation. Although high-dose nitroglycerin (>100 μg/min) has been described for this clinical scenario in limited case reports, the concern for adverse effects such as hypotension and syncope limit providers comfortability in initiating nitroglycerin at these doses. Described here is a case series of four patients who safely and effectively received high-dose nitroglycerin infusions for the management of SCAPE.

The subpleural sparing pattern is a common finding on computed tomography (CT) of the lungs. It comprises of pulmonary opacities sparing the lung peripheries, typically 1cm and less from the pleural surface. This finding has a variety of causes, including idiopathic, inflammatory, infectious, inhalational, cardiac, traumatic, and bleeding disorders. Specific disorders that can cause subpleural sparing patterns include nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), pulmonary alveolar proteinosis (PAP), diffuse alveolar hemorrhage (DAH), vaping-associated lung injury (VALI), cracked lung, pulmonary edema, pneumocystis jirovecii pneumonia (PJP), pulmonary contusion, and more recently, Coronavirus disease 2019 (COVID-19) pneumonia. Knowledge of the many etiologies of this pattern can be useful in preventing diagnostic errors. In addition, although the etiology of subpleural sparing pattern is frequently indistinguishable during an initial radiologic evaluation, the differences in location of opacities in the lungs, as well as the presence of additional radiologic findings, patient history, and clinical presentation, can often be useful to suggest the appropriate diagnosis. We did a comprehensive search on Pubmed and Google Scholar database using keywords of "subpleural sparing," "peripheral sparing," "sparing of peripheries," "CT chest," "chest imaging," and "pulmonary disease." This review aims to describe the primary differential diagnosis of subpleural sparing pattern seen on chest imaging with a strong emphasis on clinical and radiographic findings. We also discuss the pathogenesis and essential clues that are crucial to narrow the differential diagnosis.

Drowning is "the process of experiencing respiratory impairment from submersion or immersion in liquid." According to the World Health Organization, drowning claims the lives of > 40 people every hour of every day. Drowning involves some physiological principles and medical interventions that are unique. It occurs in a deceptively hostile environment that involves an underestimation of the dangers or an overestimation of water competency. It has been estimated that > 90% of drownings are preventable. When water is aspirated into the airways, coughing is the initial reflex response. The acute lung injury alters the exchange of oxygen in different proportions. The combined effects of fluid in the lungs, loss of surfactant, and increased capillary-alveolar permeability result in decreased lung compliance, increased right-to-left shunting in the lungs, atelectasis, and alveolitis, a noncardiogenic pulmonary edema. Salt and fresh water aspirations cause similar pathology. If the person is not rescued, aspiration continues, and hypoxemia leads to loss of consciousness and apnea in seconds to minutes. As a consequence, hypoxic cardiac arrest occurs. The decision to admit to an ICU should consider the patient's drowning severity and comorbid or premorbid conditions. Ventilation therapy should achieve an intrapulmonary shunt ≤ 20% or Pao2:Fio2 ≥ 250. Premature ventilatory weaning may cause the return of pulmonary edema with the need for re-intubation and an anticipation of prolonged hospital stays and further morbidity. This review includes all the essential steps from the first call to action until the best practice at the prehospital, ED, and hospitalization.

Background Currently, pulmonary edema is evaluated via surgical inspection and palpation in donor lungs, and there is no quantitative standard diagnostic tool for evaluating pulmonary edema in donor procurement and ex vivo lung perfusion (EVLP). The purpose of this study was to investigate the significance of lung weight at the donor hospital and lung weight during EVLP as a complementary parameter of transplant suitability in EVLP. Materials and methods Twenty-one of rejected human lungs were perfused in cellular EVLP. Transplant suitability was evaluated at 2 h as per standard criteria of Lund-protocol EVLP. Results Lung weight at donor hospital was significantly correlated with PaO2/FiO2 (P/F) ratio in EVLP (r = −0.44). There was a significant difference in lung weight at donor hospital between suitable cases (n = 13) and nonsuitable cases (n = 8). Light lung group (lung weight at donor hospital Conclusions Our findings demonstrate that lung weight at donor hospital, lung weight change, and lung weight at 2 h of EVLP might be a predictor of P/F ratio and transplant suitability in cellular EVLP.

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While admitted for management of hyperemesis gravidarum and preeclampsia, a 29-year-old gravida 1 para 0 patient with type 1 diabetes mellitus developed acute shortness of breath at 24 weeks gestation. Physical examination and chest X-ray findings were consistent with pulmonary edema, which in pregnancy is most often a severe complication of preeclampsia warranting delivery. The case is discussed with respect to diagnosis and management of pulmonary edema and acquired pulmonary hypertension in pregnancy, including timing and mode of delivery. Many case studies and guidelines advise caution when embarking on pregnancy with primary pulmonary hypertension; however, there is little available to guide clinical management when pulmonary hypertension secondary to fluid overload and preeclampsia develops during pregnancy.

International audience; BACKGROUND: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported.RESEARCH QUESTION: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD?STUDY DESIGN AND METHODS: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum).RESULTS: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min x m(2)), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively.INTERPRETATION: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.

Preeclampsia and eclampsia are hypertensive disorders of pregnancy associated with abnormal placental vascular development. The systemic angiogenic imbalance, endothelial dysfunction and proinflammatory state caused by abnormal placental development results in abnormalities in renal, hepatic, pulmonary and neurologic function. Neurosensory symptoms related to pregnancy induced hypertension (PIH), the most devastating of which are intracranial hemorrhage and seizure, are among the leading causes of maternal and perinatal morbidity and mortality globally, yet risk stratification strategies and targeted therapies remain elusive. Current treatment for preeclampsia with severe features is limited to delivery, antihypertensive therapy, and magnesium sulfate seizure prophylaxis. Magnesium sulfate reduces seizure rates among severe preeclamptics, but predisposes patients to weakness, uterine atony, pulmonary edema and respiratory depression. Therefore, this drug should ideally be administered only to the subset of preeclamptics who are at increased risk for neurologic complications. While there are no objective methods validated to predict eclampsia, we hypothesize that measurement of optic nerve sheath diameters, optic disc height and middle cerebral artery transcranial doppler resistance indices may be useful in identifying subclinical cerebral edema, potentially allowing us to recognize those patients at highest risk for seizures. This summary of the current literature provides an initial framework for developing more sophisticated and noninvasive methods for identifying, monitoring and treating parturients who are at highest risk for neurologic complications from preeclampsia.

Introduction A significant number of climbers on Mount Kilimanjaro are affected by altitude-related disorders. The aim of this study was to determine the main causes of morbidity and mortality in a representative cohort of climbers based on local hospital records. Methods We conducted a 2-y retrospective chart review of all patients presenting to the main referral hospital in the region after a climb on Mount Kilimanjaro, including all relevant records and referrals for postmortem studies. Results We identified 62 climbers who presented to the hospital: 47 inpatients and 15 outpatients. Fifty-six presented with high altitude illness, which included acute mountain sickness (n=8; 14%), high altitude pulmonary edema (HAPE) (n=30; 54%), high altitude cerebral edema (HACE) (n=7; 12%), and combined HAPE/HACE (n=11; 20%). The mean altitude of symptom onset ranged from 4600±750 m for HAPE to 5000±430 m for HAPE/HACE. The vast majority of inpatients (n=41; 87%) were improved on discharge. Twenty-one deceased climbers, most having died while climbing (n=17; 81%), underwent postmortem evaluation. Causes of death were HAPE (n=16; 76%), HAPE/HACE (n=3; 14%), trauma (1), and cardiopulmonary (1). Conclusions HAPE was the main cause of death during climbing as well as for hospital admissions. The vast majority of climbers who presented to hospital made a full recovery.

Healthy children may present acute mountain sickness (AMS) within a few hours after arrival at high altitudes. In few cases, serious complications may occur, including high-altitude pulmonary edema and rarely high-altitude cerebral edema. Those with preexisting conditions especially involving hypoxia and pulmonary hypertension shall not risk travelling to high altitudes. Newborn from low altitude mothers may have prolonged time to complete postnatal adaptation. The number of children and adolescents traveling on commercial aircrafts is growing, and this poses a need for their treating physicians to be aware of the potential risks of hypoxia while air traveling.

Background Electrical injuries are common in daily life. The severity of electrical injury depends on the electric current, and assessing electrical damage is difficult because there appears to be no correlation between skin burns and visceral injury. We report a case of bilateral lung injury with pulmonary hemorrhage after exposure to low-voltage electricity. Case Report A 23-year-old man was shocked by a low-voltage (110 V) electric current while at work. He had temporary loss of consciousness and twitching in the extremities, but soon regained consciousness and spontaneously stopped twitching. Electrical burn wounds were discovered on his back and forehead. Dyspnea and hemoptysis were noted. A computed tomography scan of the chest revealed patchy infiltration and consolidation of both lungs. The patient received treatment of tranexamic acid and prophylactic antibiotics for electricity-induced lung injury and pulmonary hemorrhage. Resolution of chest radiograph abnormalities was recorded on day 7. The mild dyspnea ceased approximately 2 weeks later. Why Should an Emergency Physician Be Aware of This? Electricity-induced lung injury should be considered in patients with electrical injury through a suspicious electrical current transmission pathway, respiratory symptoms, and corresponding imaging findings. Pulmonary complications can be serious and require early intervention.

In this study, a ricin toxin (RT)-induced pulmonary intoxication model was established in mice by intratracheal-delivered RT at a dose of 2× LD50. Based on this model, the histopathological evaluation of the lungs at 24 h and 48 h post-exposure was executed, and the genome-wide transcriptome of the lungs at 4, 12, 24 and 48 h post-exposure was analyzed. Histopathological analysis showed that a large number of neutrophils infiltrated the lungs at 24 h post-exposure, and slight pulmonary edema and perivascular-peribronchiolar edema appeared in the lungs at 48 h. Transcriptome analysis showed that the expression of a large number of genes related to leukocyte migration and chemotaxis consistently increased in the lungs upon exposure to RT, and the expression of genes that participate in acute phase immune and/or inflammatory response, also increased within 12 h of exposure to RT, which could be confirmed by the measurement of cytokines, such as IL-1β, TNF-α and IL-6, in bronchoalveolar lavage fluid. While the expression of genes related to cellular components of the extracellular matrix and cell membrane integrity consistently decreased in the lungs, and the expression of genes related to antioxidant activity also decreased within the first 12 h. There are 17 differentially expressed genes (DEGs) that participate in ribotoxic stress response, endoplasmic reticulum stress response or immune response in the lungs at 4 h post-exposure. The expression of these DEGs was upregulated, and the number of these DEGs accounted for about 59 % of all DEGs at 4 h. The 17 DEGs may play an important role in the occurrence and development of inflammation. Notably, Atf3, Egr1, Gdf15 and Osm, which are poorly studied, may be important targets for the subsequent research of RT-induced pulmonary intoxication. This study provides new information and insights for RT-induced pulmonary intoxication, and it can provide a reference for the subsequent study of the toxicological mechanism and therapeutic approaches for RT-induced pulmonary intoxication.

Background Heart failure complicating acute myocardial infarction marks an ominous prognosis. Killip and Kimball's classification of heart failure remains a useful tool in these patients. Lung ultrasound can detect pulmonary congestion but its usefulness in this scenario is unknown. Objective To investigate the diagnostic accuracy of lung ultrasound to predict heart failure in patients with acute myocardial infarction. Methods Patients admitted with acute myocardial infarction and without heart failure were evaluated with a lung ultrasound. The presence of B-lines was recorded and counted. The presence of new heart failure (Killip Class B, C, or D) during hospitalization was evaluated by a cardiologist blinded to the results of lung ultrasound. A ROC curve analysis was done to evaluate the diagnostic accuracy of B-lines to predict heart failure. Results 200 patients were included. Three patients were diagnosed with cardiogenic shock, 5 with acute pulmonary edema, and 17 with mild heart failure. Patients who develop heart failure had a median of 14 B-lines, however, patients who remained in Killip class A had a median of 2 (p = 0,0001). The area under the ROC curve of the sum of B-lines to predict any form of heart failure was 0,91 (CI95% 86–97). The best cut-off value was 5 B-lines, with a sensitivity of 88% (IC95% 68,8–97,5) and specificity of 81% (IC95% 73,9–86,2). Conclusion Lung ultrasound done at admission can help to predict heart failure In patients with acute myocardial infarction.

A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient’s condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE.

Severe pulmonary edema, secondary to left ventricular afterload increment, is a common problem occurring in patients receiving venoarterial extracorporeal membrane oxygenation. No consensus is currently available for its management, but several devices/procedures have been described, including an Impella device (Abiomed), balloon atrial septostomy, intraaortic balloon counterpulsation, or an additional venous cannula, as possible adjuncts. We report the feasibility and efficacy of the atrial flow regulator device (Occlutech) for left ventricular unloading in a 58-year-old patient receiving extracorporeal membrane oxygenation. However, the benefits of this device relative to simple balloon atrial septostomy need to be further investigated.

Background Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI. Material and methods Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator–activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30 mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes. Results Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c−CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI. Conclusions MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a life-saving method for patients with low-output failure after cardiac surgery. However, VA-ECMO therapy may increase left ventricular afterload due to retrograde blood flow in the aorta, which may lead to progression of pulmonary congestion. We examined the predictive value of pulmonary congestion in patients that need VA-ECMO support after cardiovascular surgery.We enrolled a total of 266 adult patients undergoing VA-ECMO support following cardiovascular surgery at a university-affiliated tertiary care centre into our single-center registry. Pulmonary edema was assessed on bedside chest X rays at day 0, 3, 5 after VA-ECMO implantation.Median age was 65 (57-72) years, 69% of patients were male and 30-day survival was 63%. At ICU-admission 20% of patients had mild, 54% had moderate and 26% showed severe pulmonary congestion. Pulmonary congestion at day 0 was not associated with outcome (adjusted HR 1.31; 95%-CI 0.89-1.93;P = 0.18), whereas pulmonary congestion at day 3 (adj. HR 2.81; 95%-CI 1.76-4.46;P0.001) and day 5 (adj. HR 3.01;95%-CI 1.84-4.93;P0.001) was significantly associated with survival. Linear regression revealed that out of left ventricular function, cardiac output, central venous saturation, maximum dobutamine and norepinephrine dose as well as fluid balance solely ECMO rotation was associated with the evolution of pulmonary congestion (P = 0.007).Pulmonary edema three and five days after ECMO implantation are associated with poor survival. Interestingly, a high VA-ECMO output was the most important determinant of worsening pulmonary congestion within the first five days.

Introduction Cardiogenic shock is difficult to diagnose due to diverse presentations, overlap with other shock states (i.e. sepsis), poorly understood pathophysiology, complex and multifactorial causes, and varied hemodynamic parameters. Despite advances in interventions, mortality in patients with cardiogenic shock remains high. Emergency clinicians must be ready to recognize and start appropriate therapy for cardiogenic shock early. Objective This review will discuss the clinical evaluation and diagnosis of cardiogenic shock in the emergency department with a focus on the emergency clinician. Discussion The most common cause of cardiogenic shock is a myocardial infarction, though many causes exist. It is classically diagnosed by invasive hemodynamic measures, but the diagnosis can be made in the emergency department by clinical evaluation, diagnostic studies, and ultrasound. Early recognition and stabilization improve morbidity and mortality. This review will focus on identification of cardiogenic shock through clinical examination, laboratory studies, and point-of-care ultrasound. Conclusions The emergency clinician should use the clinical examination, laboratory studies, electrocardiogram, and point-of-care ultrasound to aid in the identification of cardiogenic shock. Cardiogenic shock has the potential for significant morbidity and mortality if not recognized early.

Background Postextubation complication rates vary among studies. It is necessary to standardize a method to identify postextubation complications and determine their potential association with extubation failure and reintubation in critically ill adult patients. Objectives To describe immediate (up to 60 min) endotracheal postextubation complications in critically ill adult patients and determine whether these complications are associated with extubation failure. Methods Secondary analysis of a Randomized Clinical Trial that included 240 critically ill adult patients, who were eligible for extubation. Overall complications include at least one major complication (upper airway obstruction, desaturation, vomiting, post-obstructive pulmonary edema) and/or minor complications (bronchospasm, severe cough, hypertension, tachycardia, tachypnea, poor respiratory mechanics). Results Incidence of overall, major and minor complications was 71.2%, 30.9% and 62.7%, respectively. Forty (16.9%) patients failed extubation, and thirty (12.7%) were reintubated. Of 168 patients who developed a postextubation complication, 137 (81.5%) were successfully extubated. Only major complications were significantly associated with reintubation after extubation failure (p Conclusion We have observed high incidence rates of overall, major and minor complications. The development of major complications was statistically significantly associated with extubation failure and reintubation. It is still unknown whether the identification and treatment of immediate postextubation complications have positive effects on patients' clinical course or whether the complications are a mere effect of the extubation procedure.

BACKGROUND: Acute respiratory distress syndrome (ARDS) leads to progressive lung injury, which significantly impacts patient morbidity and mortality but may differ clinically between the sexes. Cytochrome P450 (CYP) 1A enzymes are protective against hyperoxic lung injury and may contribute to sex-dependent pathology. NRF2 is a critical transcriptional regulator of antioxidants and loss of NRF2 leads to severe hyperoxic lung injury and mortality in mice. NRF2 deficiencies and polymorphisms have been observed in patients with pulmonary diseases such as chronic obstructive pulmonary disease and severe asthma. No prior studies have evaluated whether there are sex-specific differences in oxygen-mediated lung injury in Nrf2(−/−) mice and there are few rescue studies. OBJECTIVE: To test the hypothesis that hyperoxia induces greater lung injury and inflammation in Nrf2(−/−) mice compared to wild type (WT) that differs between sexes, and that this phenotype will be rescued by the administration of the cytochrome P450 (CYP) 1A inducer beta-naphthoflavone (BNF). DESIGN/METHODS: Male and female 8–10-week-old WT or Nrf2(−/−) C57BL/6 mice were pre-treated with BNF (40 mg/kg) or corn oil control and exposed to hyperoxia (95% O(2)) for 68 hours. Survival, pulmonary edema, neutrophil recruitment, and lung injury scores were evaluated. Gene expression of phase II detoxification enzymes, pulmonary cytokines, and Cyp1a1/2 was quantified. CYP1A1/2 protein expression and catalytic activities were also measured. RESULTS: Hyperoxia exposure greatly reduced survival in Nrf2(−/−) mice, particularly in females. BNF treatment improved survival by 182.8% in Nrf2(−/−) females and by 41.4% in Nrf2(−/−) males as well as in WT females by 85.7%. Females had greater pulmonary edema as measured by lung weight to body weight ratios but was attenuated in all groups except Nrf2(−/−) females by BNF. Neutrophils doubled in Nrf2(−/−) lungs compared to WT in hyperoxia but were decreased in BNF-treated females of both genotypes. Pulmonary cytokine gene expression including Il-6 and Tnf-α increased in hyperoxia especially in Nrf2(−/−) mice and was unaffected by BNF. Pulmonary and hepatic Nqo1 gene expression w-as decreased in Nrf2(−/−) mice and was largely unaffected by BNF; however pulmonary Ho-1 did not vary significantly between the genotypes and was decreased in WT animals treated with BNF. Activities and protein expression of pulmonary and hepatic CYP1A1/2 were induced via BNF across all groups. Although hepatic Cyp1a2 gene expression was higher in Nrf2(−/−) males, the catalytic activity was higher in Nrf2(−/−) females. CONCLUSIONS: Hyperoxia augmented lung injury in Nrf2(−/−) mice, and pre-treatment with BNF was protective against mortality and injury, eliminating the sex-dependent survival difference in both genotypes. Our results support the hypothesis that NRF2 protects mice against lung injury, and the fact that BNF rescues the lung injury phenotype in Nrf2(−/−) mice suggests that augmented CYP1A expression by BNF may contribute to the beneficial effects. Further studies could lead to the development of BNF and other flavonoids for the prevention/treatment of hyperoxic lung injury, particularly in vulnerable patients with relative NRF2 deficiency, regardless of sex.

Combined lung-liver transplantation is a rare life-saving procedure to treat concomitant end-stage lung and liver failure. In this report, we describe the first published case of single lung and liver transplantation in a cystic fibrosis patient who had previously undergone a pneumonectomy for the treatment of an infected and destroyed right lung. We detail the lung first, sequential transplant procedure and surgical difficulties due to mediastinal shift. Emergent intraoperative renal replacement therapy was carried out before liver transplantation to overcome pulmonary edema in the transplanted lung. After fluid balance equilibration, liver transplantation was performed in good conditions. The patient is currently alive with no signs of rejection 8 years after the procedure.

Purpose Dire c t l ung u ltrasound e valuation (CLUE) technique was proven to be an accurate method for monitoring extravascular lung water in donor lungs during ex-vivo lung perfusion (EVLP) in porcine and human lung models. The aim of this study was to examine the application of CLUE in the clinical setting. Methods Lungs were evaluated in acellular EVLP with standard protocol. Ultrasound images were obtained at each point of 4 lines passing through the anterior, lateral, posterior, and diaphragmatic surfaces of each lung. Images were graded according to the percentage of B-lines and presence of consolidation. CLUE scores were calculated at the beginning (initial) and the end (final) of EVLP for the whole lung, each side and lobe using this equation: CLUE Score = (No. of Grade 1 images x 1 + No. of Grade 2 images x 2 + No. of Grade 3 images x 3 + No. of Grade 4 images x 4 + No. of Consolidation images x 5) / Total No. of images taken. Results In our clinical EVLP program, 36 lungs from 18 donors were evaluated by CLUE. Eighteen lungs were deemed suitable and were transplanted (8 double & 2 single) with no hospital mortality. There were no cases of primary graft dysfunction (PGD) grade 2 observed and one recipient had PGD 3 at 72 hours. Final CLUE score was significantly lower in suitable lungs compared to non-suitable (0.86 ± 0.4 vs 1.80 ± 0.3, p Conclusion CLUE technique shows the highest accuracy in evaluating donor lungs for transplant compared to other parameters used in EVLP. CLUE can help in improving the outcomes of lung transplant by guiding decision making through the whole process of EVLP and providing a comprehensive precise assessment of individual lungs and lobes.

Background Lung ultrasound (LUS) is useful for diagnosing pulmonary congestion, but its value in primary care remains unclear. We investigated whether LUS improved diagnostic accuracy in outpatients with heart failure (HF) suspicion. Methods and results LUS was performed on 2 anterior (A), 2 lateral (L), and 2 posterior (P) areas per hemithorax. An area was positive when ≥3 B-lines were observed. Two diagnostic criteria were used: for LUS-C1, 2 positive areas of 4 (A-L) on each hemithorax; and for LUS-C2, 2 positive areas of 6 (A-L-P) on each hemithorax. A cardiologist blinded to LUS validated HF diagnosis. 162 patients were included (age 75.6 ± 9.4 years, 70.4% women). Both LUS criteria, alone and combined with other HF diagnostic criteria, were accurate for identifying HF. LUS-C2 outperformed LUS-C1, showing remarkable specificity (0.99) and positive predictive value (0.92). LUS-C2, together with Framingham criteria, N-terminal pro-B-type natriuretic peptide, and electrocardiogram, added diagnostic value (area under the receiver operating characteristic curves 0.90 with LUS-C2 vs 0.84 without; P = .006). In the absence of N-terminal pro-B-type natriuretic peptide, LUS-C2 significantly reclassified one-third of patients above Framingham criteria and electrocardiogram (net reclassification improvement 0.65, 95% confidence interval 0.04–1.1). Conclusions LUS was accurate enough to rule-in HF in a primary care setting. The accuracy of diagnostic workup for HF in primary care is enhanced by incorporating LUS, irrespective NT-proBNP availability.

Background Despite the increasing popularity of open water swimming worldwide, swimming-induced pulmonary edema (SIPE) is a poorly recognized condition lacking established diagnostic criteria. Research Question The aim of this study was to identify diagnostic criteria of SIPE during a large open water swimming event. Study Design and Methods In this cross-sectional study, 17,904 individuals swam 1,000, 1,500, or 3,000 m in cold open water during Sweden’s largest open water swimming event in 2018 and 2019. Of 166 swimmers seeking medical attention for acute respiratory symptoms, 160 were included in the study. Medical history, symptoms, and clinical findings were collected. On-site lung ultrasound (LUS) was performed to verify pulmonary edema. Results Pulmonary edema was confirmed by LUS in 102 patients (64%); findings were unilateral in 11 (7%). Peripheral oxygen saturation was identified as a strong independent diagnostic test for pulmonary edema, with ≤ 95% as the suggested cut off based on receiver-operating characteristic curve analysis (area under the curve, 0.893; P Interpretation We suggest a clinical algorithm for diagnosis of SIPE for swimmers with acute respiratory symptoms during swimming in cold open water. Novel features of focally distributed edema in the anterior parts of the lungs, sometimes unilateral, add to this unique dataset of an underreported condition.

Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as "cytokine storm", occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.La infección por el virus de la gripe se caracteriza por síntomas que van desde la congestión leve y los dolores corporales hasta el edema pulmonar grave y la insuficiencia respiratoria. Aunque que la mayoría de las personas expuestas presentan síntomas leves y se recuperan con poca morbilidad, se estima que cada año 500.000 personas en todo el mundo fallecen por las complicaciones relacionadas con esta infección. En estos casos graves, se produce una respuesta inflamatoria exagerada, conocida como «tormenta de citocinas», que causa daños en la barrera epitelial respiratoria y el desarrollo del síndrome de distrés respiratorio agudo. Los datos de estudios retrospectivos en humanos, así como de modelos animales experimentales de infección por el virus de la gripe, resaltan la delgada línea que existe entre una respuesta inmunitaria excesiva y una inadecuada, cuando la respuesta del huésped debe mantener el equilibrio entre el aclaramiento viral y la inflamación exagerada. Los moduladores farmacológicos de la inflamación actuales, incluidos los corticoides y las estatinas, no han tenido éxito a la hora de mejorar los resultados de la infección por el virus de la gripe. Hemos publicado que la amplitud de la respuesta inflamatoria está regulada por la actividad del complejo de ensamblaje de cadenas lineales de ubiquitina (LUBAC, por sus siglas en inglés) y que la atenuación de la actividad de LUBAC protege durante la infección grave por este virus. La modulación terapéutica de la actividad de LUBAC puede ser crucial para mejorar los resultados, ya que funciona como un reóstato molecular de la respuesta del huésped. Aquí revisamos la evidencia al respecto de la modulación de la inflamación para mejorar el daño pulmonar inducido por la infección por el virus de la gripe, los datos sobre las estrategias antiinflamatorias actuales y las posibles nuevas vías para tratar la inflamación viral y mejorar los resultados.