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Any insult to the central nervous system can lead to the rare occurrence of neurogenic pulmonary oedema (NPO). It is usually associated with significant neurological injury (eg, subarachnoid haemorrhage or traumatic brain injury) with a relatively rapid onset. As an exception to this observation, we report a middle-aged woman who developed NPO 72 hours after the onset of a subtle but evolving right middle cerebral artery infarction confirmed on CT. Aggressive use of diuretics and vasodilators, as is normally the case for cardiogenic pulmonary oedema, can compromise cerebral blood flow and the ischaemic penumbra. This case illustrates how the diagnostic and therapeutic challenges were successfully addressed with the aid of bedside ultrasonography and close haemodynamic monitoring to reverse the respiratory failure while protecting the brain.

Purpose: A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. Results: 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI − 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (− 1.17 ml/kg, 95% CI − 1.87 to − 0.44). Conclusions: IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).

Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: βSP-D = 6.79 units/log10 pg/mL, βsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: βSP-D = 3.28 units/log10 pg/mL, βsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.

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.

Pigoń, Katarzyna, Ryszard Grzanka, Ewa Nowalany-Kozielska, and Andrzej Tomasik. Severe respiratory failure developing in the course of high-altitude pulmonary edema in an alpinist with COVID-19 pneumonia: a case report.

Background. Diagnosing and discriminating non-cardiogenic interstitial syndrome (NCIS) and cardiogenic pulmonary edema (CPE) is notoriously difficult in a mixed intensive care unit (ICU) population. We hypothesized that a comprehensive lung ultrasound exam can be used to accurately diagnose interstitial syndrome and can discriminate between NCIS and CPE.Methods. A single center prospective diagnostic accuracy study was used as derivation cohort and a post-hoc analysis of a multi-center prospective observational study as validation cohort. Consecutive adult ICU patients that received a lung ultrasound examination for clinical or study purposes were included. The reference standard was the diagnosis interstitial syndrome (NCIS or CPE) or non-interstitial syndromes (other pulmonary diagnoses and no pulmonary diagnoses) at the moment of examination based on full post-hoc clinical chart review except lung ultrasound. The index test was a comprehensive lung ultrasound examination performed and scored by a researcher blinded to clinical information.Results. 101 patients were included in the derivation and 125 in validation cohort. In the derivation cohort, patients with interstitial syndrome (n=56) were reliably discriminated from other patients based on the presence of a B-pattern (defined as ≥3 B-lines in one frame) with an accuracy of 94.7% (sens 90.9%, spec 91.1%), while specificity was higher for a bilateral B-pattern (accuracy 86.0%; sens 74.5%, spec 100%). For the discrimination of NCIS (n=29) from CPE (n=27), the presence of bilateral pleural line abnormalities had the highest diagnostic accuracy (94.6%; sens 89.3%, spec 100%) followed by consolidation (76.8%; sens 69.0%, spec 85.2%) and subtle lung sliding (67.9%; sens 62.1%, spec 74.1%). A diagnostic algorithm (BLUISH protocol) using B-pattern and bilateral pleural abnormalities had an accuracy of 0.86 (95%CI 0.77-0.95) for diagnosis and discrimination of interstitial syndromes. In the validation cohort, which included 125 patients with interstitial syndrome, pleural line abnormalities discriminated NCIS (n=101) from CPE (n=24) with a sensitivity of 30% (95%CI 21-40%) and a specificity of 100% (95%CI: 86-100%). Conclusions. Lung ultrasound can be used to diagnose and discriminate interstitial syndromes in ICU patients with moderate to good accuracy. Pleural line abnormalities are highly specific for NCIS, but sensitivity is limited.

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.

Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF).In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments.In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

Flash pulmonary oedema can occur as a result of multiple triggers that may act independently or in concert. One such precipitating factor is bilateral renal artery stenosis which can be treated either with revascularisation or with medical therapy. Unilateral renal artery stenosis, however, is a rare cause of flash pulmonary oedema, especially when the contralateral kidney is still functional. We describe a case of an elderly woman with a history of heart failure with preserved ejection fraction and multiple hospitalisations for hypertensive crisis and flash pulmonary oedema who was found to have right, ostial renal artery stenosis that was treated with stent placement.

Enterovirus A71 (EV-A71) is one of the major pathogens responsible for hand, foot, and mouth disease (HFMD). Many HFMD outbreaks have been reported throughout the world in the past decades. Compared with other viruses, EV-A71 infection is more frequently associated with severe neurological complications and even death in children. EV-A71 can also infect adults and cause severe complications and death, although such cases are very uncommon. Although fatal cases of EV-A71 infection have been reported, the underlying mechanisms of EV-A71 infection, especially the mode of viral spread into the central nervous system (CNS) and mechanisms of pulmonary edema, which is considered to be the direct cause of death, have not yet been fully clarified, and more studies are needed. Here, we first summarize the pathological findings in various systems of patients with fatal EV-A71 infections, focussing in detail on gross changes, histopathological examination, tissue distribution of viral antigens and nucleic acids, systemic inflammatory cell infiltration, and tissue distribution of viral receptors and their co-localization with viral antigens. We then present our conclusions about viral dissemination, neuropathogenesis, and the mechanism of pulmonary edema in EV-A71 infection, based on pathological findings.

Background: Transfusion-related acute lung injury (TRALI) is a severe complication of plasma transfusion, though use of solvent/detergent pooled plasma (SDP) has nearly eliminated reported TRALI cases. The goal of this study was to investigate TRALI incidence in the intensive care unit (ICU) following replacement of quarantined, male-only, fresh frozen plasma (qFFP) by SDP for routine use. Methods:We conducted a retrospective multicenter observational before-after cohort study during two six-month periods, before (April to October 2014) and after introduction of SDP (April to October 2015), taking into account a six-month wash-out period. One secondary and four tertiary academic hospitals participated.Results:Admitted to the ICU were 8944 patients during both inclusion periods. 1171 qFFP units were transfused in 376 patients in the qFFP, and 396 during the before and after periods respectively in the SDP period. A full patient chart review was performed in 300 patients that received ≥1 units of plasma and had a PaO2/FiO2-ratio (P/F-ratio) Conclusion:Implementation of SDP lowered the incidence of TRALI in which plasma products were implicated, though not significantly. TRALI can still occur as a result of SDP transfusion. Developing TRALI in the ICU was associated with high mortality rates, therefore clinicians should remain vigilant.

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

Aims: Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema (ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE. Methods and results: A randomized, multicentre, open-label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in-hospital all-cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30-day mortality and SAE. Analyses were made on an intention-to-treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in-hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratio[RR] 0.71, 95% confidence interval [CI] 0.29–1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22–0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30–0.92; p = 0.03). Conclusion: Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group. Instituto de Salud Carlos III supported with funds from the Spanish Ministry of Health and FEDER (PI17/01590) No data IDR 2020 18.174 JCR (2021) Q1, 7/143 Cardiac & Cardiovascular Systems 5.231 SJR (2021) Q1, 7/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEC

Background: The remote dielectric sensing (ReDS) system is a recently introduced non-invasive technology used to easily estimate the degree of lung fluid volume without any expert techniques. In the previous literature, ReDS values had a moderate correlation with invasively measured pulmonary artery wedge pressure (PAWP), the gold standard for representing left heart preload. Considering the mechanism of ReDS technology, ReDS values may be inappropriately elevated in the presence of pleural effusion (PE), and the ability of the ReDS system to estimate PAWP may decrease in such a situation. Methods: In-hospital patients with cardiovascular diseases underwent computed tomography, and the presence of pleural effusion (PE) was evaluated. The measurement of ReDS values using the ReDS system and the measurement of PAWP using invasive right heart catheterization were also performed simultaneously. The impact of the presence of PE on the relationship between the ReDS values and PAWP was evaluated. Results: A total of 59 patients (79 years, 30 male) were included. The median ReDS value was 25% (IQR: 22%, 30%) and the median PAWP level was 13 (IQR: 10, 18) mmHg. Of these patients, 11 had PE. PAWP was not significantly different between the two groups, whereas the ReDS values in the PE group were significantly higher than in the no-PE group. The impact of the presence of PE on the ReDS values was significant, with a beta value of 6.61 (95% confidence interval: 4.80–8.42, p < 0.001) upon adjusting for the levels of PAWP. Conclusions: We should pay attention to interpreting ReDS values when assessing the degree of pulmonary congestion in patients with PE, because ReDS values may be inappropriately elevated in this cohort.

Namen: Ugotoviti, ali lahko z aplikacijo visokih odmerkov vitamina C zmanjšamo tveganje za pljučni edem po porodu pri bolnicah s težko preeklampsijo. Hipotezi: Vitamin C v prvih treh dneh po porodu pri bolnicah s težko preeklampsijo zmanjša količino zunajžilne pljučne tekočine merjeno z ultrazvočno (UZ) preiskavo pljuč. Vitamin C v prvih treh dneh po porodu pri bolnicah s težko preeklampsijo zmanjša koncentracijo biokemičnih označevalcev oksidativnega stresa v urinu. Utemeljitev: Preeklampsija je vodilni vzrok za pojav obporodnega pljučnega edema. Pomemben vzrok za to je okvarjena endotelna funkcija in posledično povečana žilna prepustnost. Eden od možnih vzrokov za endotelno disfunkcijo pri preeklampsiji je tudi povečan oksidativni stres. Antioksidant vitamin C pri življenjsko ogroženih bolnikih dokazano zmanjša žilno prepustnost. Vpliv vitamina C na potek težke preeklampsije po porodu ni raziskan. Metode: Monocentrična, randomizirana, s placebom kontrolirana, dvojno slepa študija. Štiriintrideset bolnic s težko preeklampsijo je prejelo intravensko vitamin C (1,5g/6h) (n=17) ali placebo (n=17) prve tri dni po porodu. UZ pljuč je bil narejen enkrat dnevno, od prvega do tretjega dne po porodu. Količino zunajžilne pljučne tekočine smo opredelili z ECS (echo comet score seštevek števila B-linij v 28-interkostalnih oknih). V urinu odvzetem prvi in tretji dan po porodu so bile določene vrednosti štirih označevalcev oksidativnega stresa: ditirozin, 8-hidroksi-2-deoksigvanozin (8- OHdG), 8-izoprostan in N-epsilon-Heksanoil-Lizin (HEL). Uporabljen je bil Mann-Whitney U-test za statistično primerjavo med skupinama. Vrednost p ? 0,05 je bila upoštevana za statistično pomembno. Preučevani izidi: Pri dan po porodu nismo našli statistično pomembne razlike v ECS med skupinama (mediana 23 (inter-kvartilni razmik (IQR) 21–61) vs 18 (IQR 8–35) p = 0,31). Drugi in tretji dan po porodu je bil ECS statistično pomembno manjši v skupini, ki je prejemala vitamin C, v primerjavi s placebom (8 (IQR 3–14) vs 35 (IQR 15–78) p = 0,03 in 5 (IQR 3–10) vs 18 (IQR 18– 44) p = 0,04). Vrednosti ditirozina in 8-OHdG se prvi dan po porodu med skupinama niso statistično pomembno razlikovale (p = 0,23 in p = 0,77). Bile pa so pomembno manjše tretji dan po porodu v skupini, ki je prejemala vitamin C (p = 0,04 in p = 0,03). Vrednosti 8-izoprostana in HEL se niso statistično pomembno razlikovale ne prvi (p = 0,41 in p = 0,42), ne tretji (p = 0,25 in p = 0,24) dan po porodu. Zaključek: Visoki intravenski odmerki vitamina C pri bolnicah s težko preeklampsijo niso zmanjšali količine zunajžilne pljučne tekočine ali markerjev oksidativnega stresa v urinu prvi dan po porodu. Vplivali pa so na zmanjšanje zunajžilne pljučne tekočine drugi in tretji dan po porodu ter na zmanjšanje nivojev ditirozina in 8-OHdG (markerjev oksidativne poškodbe proteinov in DNA) tretji dan po porodu. Objective: To determine if vitamin C in high doses reduces extravascular lung water in women with severe preeclampsia postpartum. Hypotheses: Vitamin C in the first three days postpartum reduces extravascular lung water assessed by lung ultrasound in patients with severe preeclampsia. Vitamin C in the first three days postpartum reduces urinary levels of oxidative stress biomarkers. Rationale: Preeclampsia is the leading cause of peripartum pulmonary edema which occurs, at least in part, due to endothelial dysfunction and increased vascular permeability. Oxidative stress contributes significantly to the development of preeclampsia and its clinical course. Vitamin C was proven to be beneficial in reducing vascular permeability in critically ill patients. It has been shown that the use of vitamin C in pregnancy was not effective for primary or secondary prevention of preeclampsia. The effect of vitamin C on preeclampsia postpartum as a tertiary prevention measure, i.e., reducing risks of complications once preeclampsia has already occurred, is not known. Population: Consecutively admitted patients with singleton pregnancies complicated by severe preeclampsia. Methods: Single-center, randomized, placebo-controlled, double-blind trial. Thirty-four patients received vitamin C (1.5 g/6 hours) (n = 17) or placebo (n = 17) intravenously at days 1, 2, and 3 postpartum. A lung ultrasound was performed once daily in the first three days following delivery. Echo Comet Score (ECS) was obtained using the 28-rib interspaces technique. Urine was collected on postpartum days 1 and 3. It was analysed for four biomarkers of oxidative stress: dityrosine, 8-hydroxy-2-deoxyguanosine (8- OHdG), 8-isoprostane, and N-epsilon-Hexanoyl-Lysine (HEL). Mann-Whitney-U test was used to compare vitamin C vs placebo groups. A p 䁤 0.05 was considered statistically significant. Main outcome measures: ECS on day 1 postpartum was the primary outcome studied. ECS on days 2 and 3 postpartum as well as urinary biomarkers of oxidative stress (dityrosine, 8- OHdG, 8-isoprostane, and HEL, normalized for urinary creatinine), on days 1 and 3 postpartum were analyzed as secondary outcomes. Results: There was no significant difference in ECS on day 1 (median 23 (inter-quartile range (IQR) 21–61) vs 18 (IQR 8–35) p = 0.31). On days 2 and 3, ECS was significantly lower in the vitamin C group compared to the placebo (8 (IQR 3–14) vs 35 (IQR 15–78) p = 0.03 and 5 (IQR 3–10) vs 18 (IQR 18– 44) p = 0.04, respectively). Dityrosine and 8-OHdG values did not differ significantly between the two study groups on day 1 after delivery (p = 0.23 and p = 0.77, respectively), but were significantly lower in the vitamin C group compared to the placebo group on day 3 after delivery (p = 0.04 and p = 0.03, respectively). Values of 8-isoprostane and HEL did not differ significantly between the two study groups on day 1 (p = 0.41 and p = 0.42, respectively), as well as on day 3 after delivery (p = 0.25 and p = 0.24, respectively). Conclusion: High dose of intravenous vitamin C did not reduce the amount of extravascular lung water or decrease markers of oxidative stress in postpartum patients with severe preeclampsia on day 1 after delivery. It seems, however, it has a delayed effect with a reduction in extravascular lung water detected on ultrasound on days 2 and 3 following delivery and a reduction of urinary levels of dityrosine and 8-OHdG (markers of protein and DNA oxidative damage, respectively) on day 3 after delivery.

Surveillance of Severe Maternal Outcome (SMO), which is the combination of Maternal Near Miss (MNM) and Maternal Mortality, in the Metro East health district, Western Cape province, South Africa, has given useful insight into its incidence and contributing factors. The MNM-ratio in Metro East was 8.6 per 1,000 livebirths in 2014-2015, and the Maternal Mortality Ratio 49.7 per 100,000 live births, resulting in a SMO-ratio of 9.1 per 1,000 live births. This MNM-ratio identified for Metro East is comparable to the median MNM-ratio reported for middle-income countries of 9.6 per 1,000 livebirths, with a median MNM-ratio of 15.9 per 1,000 in lower-middle and 7.8 per 1,000 in upper-middle income countries. The MNM-ratio in Metro East was slightly higher than the ratio in other regions in South Africa, but case fatality among women with MNM was lower, possibly illustrating a relatively higher quality of care. The main causes of SMO in Metro East were hypertensive disorders of pregnancy and major obstetric haemorrhage, which are similar to the commonest causes of SMO in other middle-income countries, and worldwide. Associated factors were a positive HIV-serostatus, birth by caesarean section, preeclampsia and obesity. The relatively large differences in the incidence of SMO between different regions in South Africa, and between different middle-income countries appear to be at least partly explained by difficulties in applying the MNM-tool as proposed by the World Health Organization. We suggest that the tool is currently mostly valuable for assessments of SMO in the local setting, rather than for comparisons between regions or countries. Analyses of SMO in Metro East provided useful insights into local causes: obstetric haemorhage relatively frequently due to placental abruption, often in combination with intrauterine fetal death and hypertension. In contrast with most other settings, hysterectomy for maternal sepsis was as common as for peripartum haemorrhage, both associated with cesarean section. Severe complications of hypertensive disorders of pregnancy were frequent, with pulmonary edema being a particularly common complication leading to maternal death. Early detection and management of preeclampsia, monitoring of fluid balance and cardiac evaluation when pulmonary edema persists, were preventive suggestions. Audit helped identify lessons learned: for all women with SMO, not attending antenatal care was a woman-related factor and missing the diagnosis or not starting adequate management in time were factors at the level of the health worker. In almost a quarter of cases, different management could have prevented SMO. Life style changes, understanding maternal behavior, but also recognizing SMO in an early stage and adequate multidisciplinary management in a critical care setting could reduce SMO and improve its outcomes. Health workers found the identification and analysis of MNM a valuable addition to the already existing confidential enquiry into maternal deaths in South Africa. A national MNM audit was recommended to address causes and improve maternal outcomes. A list of diagnosis additional to those mentioned in the existing MNM tool would help identifying local causes of MNM more precisely. Simplification of the tool would be welcomed in this setting.

Surveillance of Severe Maternal Outcome (SMO), which is the combination of Maternal Near Miss (MNM) and Maternal Mortality, in the Metro East health district, Western Cape province, South Africa, has given useful insight into its incidence and contributing factors. The MNM-ratio in Metro East was 8.6 per 1,000 livebirths in 2014-2015, and the Maternal Mortality Ratio 49.7 per 100,000 live births, resulting in a SMO-ratio of 9.1 per 1,000 live births. This MNM-ratio identified for Metro East is comparable to the median MNM-ratio reported for middle-income countries of 9.6 per 1,000 livebirths, with a median MNM-ratio of 15.9 per 1,000 in lower-middle and 7.8 per 1,000 in upper-middle income countries. The MNM-ratio in Metro East was slightly higher than the ratio in other regions in South Africa, but case fatality among women with MNM was lower, possibly illustrating a relatively higher quality of care. The main causes of SMO in Metro East were hypertensive disorders of pregnancy and major obstetric haemorrhage, which are similar to the commonest causes of SMO in other middle-income countries, and worldwide. Associated factors were a positive HIV-serostatus, birth by caesarean section, preeclampsia and obesity. The relatively large differences in the incidence of SMO between different regions in South Africa, and between different middle-income countries appear to be at least partly explained by difficulties in applying the MNM-tool as proposed by the World Health Organization. We suggest that the tool is currently mostly valuable for assessments of SMO in the local setting, rather than for comparisons between regions or countries. Analyses of SMO in Metro East provided useful insights into local causes: obstetric haemorhage relatively frequently due to placental abruption, often in combination with intrauterine fetal death and hypertension. In contrast with most other settings, hysterectomy for maternal sepsis was as common as for peripartum haemorrhage, both associated with cesarean section. Severe complications of hypertensive disorders of pregnancy were frequent, with pulmonary edema being a particularly common complication leading to maternal death. Early detection and management of preeclampsia, monitoring of fluid balance and cardiac evaluation when pulmonary edema persists, were preventive suggestions. Audit helped identify lessons learned: for all women with SMO, not attending antenatal care was a woman-related factor and missing the diagnosis or not starting adequate management in time were factors at the level of the health worker. In almost a quarter of cases, different management could have prevented SMO. Life style changes, understanding maternal behavior, but also recognizing SMO in an early stage and adequate multidisciplinary management in a critical care setting could reduce SMO and improve its outcomes. Health workers found the identification and analysis of MNM a valuable addition to the already existing confidential enquiry into maternal deaths in South Africa. A national MNM audit was recommended to address causes and improve maternal outcomes. A list of diagnosis additional to those mentioned in the existing MNM tool would help identifying local causes of MNM more precisely. Simplification of the tool would be welcomed in this setting.

We aim to investigate the additive effect of B-lines on lung ultrasound (LUS) for predicting outcome in patients with heart failure (HF) when combined with conventional assessment of clinical congestion.This study prospectively enrolled 117 hospitalized HF patients (61 ± 16 years, 70.1% males) who underwent congestion assessment by the 'wet/dry' status, clinical congestion score (CCS), and B-lines on LUS. The primary endpoint was all-cause mortality or hospitalization for HF during the 180-day follow-up after discharge. The 'Wet', CCS ≥ 3, and B-lines5, indicators of congestion positive (+), were observed in 83.8%, 76.1%, and 70.1% of the patients on admission, respectively; and the numbers significantly decreased to 41.9%, 41.9%, and 35.9% at discharge, respectively. The agreement between the 'wet/dry' status and B-lines (58.1%) or between CCS and B-lines (56.4%) was moderate at discharge, in terms of both positive and both negative. By incorporating the B-lines with assessment of clinical congestion, the patients at discharge were divided into three phenotypes as clinical congestion (+), clinical congestion (-) with B-lines (+), and clinical congestion (-) with B-lines (-). The Kaplan-Meier analysis showed a better survival in the both (-) group ('wet/dry' with B-lines: Chi-square 10.591, P = 0.005; CCS with B-lines: χThe combination of B-lines on LUS and conventional assessment helped to identify new phenotypes of congestion that aid in the risk stratification of discharged HF patients. Further investigation is warranted to determine whether this strategy could be adopted as a guide for decongestion therapy.

This case demonstrates the value of perioperative point-of-care ultrasound for rapid bedside evaluation and treatment of pulmonary oedema in an infant. A nine-week-old male infant undergoing cleft lip repair received significant intravenous fluid resuscitation for intraoperative hypotension. After uneventful extubation, he developed increased work of breathing and a gradual decline in oxygen saturation despite supplemental oxygen by way of a facemask. Lung point-of-care ultrasound revealed confluent B-lines in multiple lung fields, consistent with pulmonary oedema, likely from fluid overload. He was treated with furosemide resulting in clinical improvement within 30 minutes.

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.

Pulmonary congestion (PC) expressed by residual lung ultrasound B-lines (LUS-BL) could exist in some discharged heart failure (HF) patients, which is a known determinant of poor outcomes. Detection efficacy for PC is suboptimal with widely used imaging modalities, like X-ray or echocardiography, while lung ultrasound (LUS) can sufficiently detect PC by visualizing LUS-BL. In this trial, we sought to evaluate the impact LUS-BL-guided intensive HF management post-discharge on outcome of HF patients discharged with residual LUS-BL up to 1 year after discharge. IMP-OUTCOME is a prospective, single-centre, single-blinded, randomized cohort study, which is designed to investigate if LUS-BL-guided intensive HF management post-discharge in patients with residual LUS-BL could improve the clinical outcome up to 1 year after discharge or not.After receiving the standardized treatment of HF according to current guidelines, 318 patients with ≥3 LUS-BL assessed by LUS within 48 h before discharge will be randomly divided into the conventional HF management group and the LUS-BL-guided intensive HF management group at 1:1 ratio. Patient-related basic clinical data including sex, age, blood chemistry, imaging examination, and drug utilization will be obtained and analysed. LUS-BL will be assessed at 2 month interval post-discharge in both groups, but LUS-BL results will be enveloped in the conventional HF management group, and diuretics will be adjusted based on symptom and physical examination results with or without knowing the LUS-BL results. Echocardiography examination will be performed for all patients at 12 month post-discharge. The primary endpoint is consisted of the composite of readmission for worsening HF and all-cause death during follow up as indicated. The secondary endpoints consisted of the change in the New York Heart Association classification, Duke Activity Status Index, N terminal pro brain natriuretic peptide value, malignant arrhythmia event and 6 min walk distance at each designed follow up, echocardiography-derived left ventricular ejection fraction, and number of LUS-BL at 12 month post-discharge. Safety profile will be recorded and managed accordingly for all patients.This trial will explore the impact of LUS-BL-guided intensive HF management on the outcome of discharged HF patients with residual LUS-BL up to 1 year after discharge in the era of sodium-glucose cotransporter-2 inhibitors and angiotensin receptor blocker-neprilysin inhibitor.ClinicalTrials.gov: NCT05035459.

Objectives The aim of the study was to determine whether cardiogenic pleural effusion in cats is associated with a lower risk of arterial thromboembolism (ATE) compared with cats with cardiac disease without evidence of pleural effusion. Methods A cross-sectional study was conducted on owned cats with natural occurring cardiac diseases. Cats included were classified in three groups: those with cardiac disease but no evidence of congestive heart failure (CHF); those with evidence of cardiogenic pulmonary oedema; and those with evidence of cardiogenic pleural effusion. Prevalence of ATE was calculated and the variables analysed for an association with this outcome were the presence and type of CHF, sex and neuter status, age, breed, type of cardiac diseases and left atrial (LA) dimension. A multivariable logistic regression model was used to fit the association between ATE and these variables. Results A total of 366 cats with cardiac disease met the inclusion criteria: 179 were included in the group with cardiac disease but no evidence of CHF, 66 in the group with evidence of cardiogenic pulmonary oedema and 121 in the group with evidence of cardiogenic pleural effusion. Prevalence of ATE (58/366 [15.8%]) was significantly different among groups (with no evidence of CHF, 28/179 [15.6%]; with evidence of cardiogenic pulmonary oedema, 22/66 [33.3%]; with evidence of cardiogenic pleural effusion, 8/121 [6.6%]; P Conclusions and relevance Presence of cardiogenic pleural effusion is associated with a lower risk of developing ATE, while LA enlargement is a risk factor for ATE.

Fluid overload is a common complication in patients with CKD, particularly patients with kidney failure, a population with a very high risk for pulmonary edema. Lung ultrasound is now a well-validated technique that allows for reliable estimates of lung water in clinical practice. Several studies in patients with kidney failure documented a high prevalence of asymptomatic lung congestion of moderate to severe degree in this population, and this alteration was only weakly related with fluid excess as measured by bioimpedance spectroscopy. Furthermore, in these studies, lung congestion correlated in a dose-dependent fashion with death risk. In the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk Kidney Failure Patients with Cardiomyopathy (LUST) trial, a treatment strategy guided by lung ultrasound safely relieved lung congestion but failed to significantly reduce the risk for a combined end point including death, nonfatal myocardial infarction, and decompensated heart failure. However, in line with three trials in patients with heart failure, a post hoc analysis of the LUST trial showed that the use of lung ultrasound reduces the risk for repeated episodes of acute heart failure and repeated cardiovascular events. Given the high cardiovascular risk of pulmonary edema in patients with predialysis CKD, defining the epidemiology of lung congestion in this population is a public health priority. Specific trials in this population and additional trials in patients with kidney failure will establish whether targeting lung congestion at an asymptomatic phase may improve the severe cardiovascular prognosis of both patients predialysis and patients on dialysis.

The term transfusion-related acute lung injury (TRALI) was coined in 1985 to describe acute respiratory distress syndrome (ARDS) after transfusion, when another ARDS risk factor was absent; TRALI cases were mostly associated with donor leukocyte antibody. In 2001, plasma from multiparous donors was implicated in TRALI in a randomized controlled trial in Sweden. In 2003 and in many years thereafter, the U.S. Food and Drug Administration reported that TRALI was the leading cause of death from transfusion in the United States. In 2003, the United Kingdom was the first among many countries to successfully reduce TRALI using male-predominant plasma. These successes are to be celebrated. Nevertheless, questions remain about the mechanisms of non-antibody TRALI, the role of blood products in the development of ARDS in patients receiving massive transfusion, the causes of unusual TRALI cases, and how to reduce inaccurate diagnoses of TRALI in clinical practice. Regarding the latter, a study in 2013-2015 at 169 U.S. hospitals found that many TRALI diagnoses did not meet clinical definitions. In 2019, a consensus panel established a more precise terminology for clinical diagnosis: TRALI type I and TRALI type II are cases where transfusion is the likely cause, and ARDS are cases where transfusion is not the likely cause. For accurate diagnosis using these clinical definitions, critical care or pulmonary expertise is needed to distinguish between permeability versus hydrostatic pulmonary edema, to determine whether an ARDS risk factor is present, and, if so, to determine whether respiratory function was stable within the 12 hours before transfusion.

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.

Small-breed dogs commonly have concurrent myxomatous mitral valve disease (MMVD) and lower respiratory tract disease (LRTD).Small-breed dogs with preclinical MMVD and concurrent LRTD have more B-lines on point-of-care lung ultrasound (POC-LUS) compared to dogs without concurrent LRTD and are prone to misdiagnose as cardiogenic pulmonary edema (CPE).A total of 114 small-breed dogs with preclinical MMVD.A prospective study was conducted, in which POC-LUS was obtained and the number of B-lines was calculated by a single clinician using the Veterinary Bedside Lung Ultrasound Examination protocol. The presence/absence of LRTD was assessed by clinicians blinded to the POC-LUS results.Fifty and 64 dogs were in ACVIM stage B1 and B2, respectively. The presence of LRTD was prevalent in 74.6% (85/114) of small-breed dogs with preclinical MMVD. When a previously reported criterion for CPE diagnosis (≥2 sites with3 B-lines/site) was applied, false-positive results were observed in 15.8% (18/114) of dogs with preclinical MMVD. The summated number of B-lines (3 vs. 1, P = .003), as well as the false-positive rate (20% vs 3%, P = .04), were significantly higher in dogs with LRTD compared with dogs without LRTD. Multivariable logistic regression showed the presence of abnormalities other than B-line on POC-LUS (eg, thickened pleura or consolidation) could predict false-positive results (odds ratio = 3.75, 95% confidence intervals 1.12-12.54; P = .03) after adjustment for other clinical and echocardiographic factors.Concurrent LRTD and abnormalities other than B-lines should be considered in the interpretation of POC-LUS in MMVD dogs.

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.

Herein, we present an uncommon forensic case of death by asphyxia. The victim was a woman whose body at death scene investigation (DSI) was discovered beside an ottoman storage bed. According to the rescue team, who had moved the body before our arrival, the body was originally found in the prone position and stuck with the neck, thorax and arms within the bed. Examination of the body showed hypostasis that was mainly distributed to the face and the lower chest while sparing the neck and the upper chest. The face was markedly swollen, and the eyes were congested with blood. Dissection and histology revealed pulmonary oedema and emphysema of both lungs. Integrating circumstantial, radiology and autopsy data, it was established that the victim, while trapped between the mattress and the edge of the ottoman storage bed, died by mechanical asphyxia due to cervical-thoracic compression and postural asphyxia acting simultaneously.

Immersion pulmonary edema is a rare, underrecognized, and potentially lethal pathology developing during scuba diving and other immersion-related activities (swimming or apnoea). Physiopathology is complex and not fully understood, but its mechanisms involve an alteration of the alveolo-capillary barrier caused by transcapillary pressure elevation during immersion, leading to an accumulation of fluid and blood in the alveolar space. Diagnosis remains a challenge for clinicians and forensic practionner. The symptoms begin during ascent, with cough, frothy sputum, and hemoptysis. Auscultation reveals signs of pulmonary edema. Pulmonary CT scan, which is the radiological exam of choice, shows ground glass opacities and interlobular thickening, eventually demonstrating a patterned distribution, likely in the anterior segments of both lungs. Apart from the support of vital functions, there is no specific treatment and hyperbaric oxygen therapy is not systematically recommended. We present a case of fatal IPE occurring in a recreational diver who unfortunately died shortly after his last dive. Diagnosis was made after complete forensic investigations including post-mortem-computed tomography, complete forensic autopsy, histological examination, and toxicological analysis.

Flash pulmonary oedema is a life-threatening complication of renal artery stenosis. We report a very rare complication in a patient with bilateral atherosclerotic renal artery stenosis who underwent unilateral renal artery angioplasty because of recurrent flash pulmonary oedema. Shortly after the procedure, she developed extreme polyuria (over 201 in the first 48 h) with massive natriuresis (1000 mmol urinary sodium excretion in the first 24 h). Most likely, the occurrence of this phenomenon is related to the fact that her contralateral kidney was atrophic and no longer functioning due to total renal artery occlusion. We provide an overview of the literature and discuss several mechanisms that may contribute to the occurrence of this exaggerated natriuretic response in patients with one-kidney renovascular hypertension who undergo renovascular revascularization. We recommend close monitoring of natriuresis in such patients and - if needed - administration of intravenous isotonic saline (0.9% NaCl) to prevent hypovolemia.

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.

Abstract: Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may devel-op a susceptibility to immune responses in their lungs. Our previous reports delineated the ability of QIAPI 1®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Considering the commonalities of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1® against pentavalent As-induced lung toxicity by examining the pul-monary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. The As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multi-nucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial ede-ma. The group treated with As and QIAPI 1® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1® can be recommended as antagonistic to As-induced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.

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.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/, Purpose: Fluid management is challenging in malaria patients given the risks associated with intravascular fluid depletion and iatrogenic fluid overload leading to pulmonary oedema. Given the limitations of the physical examination in guiding fluid therapy, we evaluated point-of-care ultrasound (POCUS) of the inferior vena cava (IVC) and lungs as a novel tool to assess volume status and detect early oedema in malaria patients. Methods: To assess the correlation between IVC and lung ultrasound (LUS) indices and clinical signs of hypovolaemia and pulmonary oedema, respectively, concurrent clinical and sonographic examinations were performed in an observational study of 48 malaria patients and 62 healthy participants across age groups in Gabon. Results: IVC collapsibility index (CI) ≥ 50% on enrolment reflecting intravascular fluid depletion was associated with an increased number of clinical signs of hypovolaemia in severe and uncomplicated malaria. With exception of dry mucous membranes, IVC-CI correlated with most clinical signs of hypovolaemia, most notably sunken eyes (r = 0.35, p = 0.0001) and prolonged capillary refill (r = 0.35, p = 0.001). IVC-to-aorta ratio ≤ 0.8 was not associated with any clinical signs of hypovolaemia on enrolment. Among malaria patients, a B-pattern on enrolment reflecting interstitial fluid was associated with dyspnoea (p = 0.0003), crepitations and SpO2 ≤ 94% (both p < 0.0001), but not tachypnoea (p = 0.069). Severe malaria patients had increased IVC-CI (p < 0.0001) and more B-patterns (p = 0.004) on enrolment relative to uncomplicated malaria and controls. Conclusion: In malaria patients, POCUS of the IVC and lungs may improve the assessment of volume status and detect early oedema, which could help to manage fluids in these patients.

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.

Application of artificial intelligence (AI) to improve clinical diagnosis is a burgeoning field in human and veterinary medicine. The objective of this prospective, diagnostic accuracy study was to determine the accuracy, sensitivity, and specificity of an AI-based software for diagnosing canine cardiogenic pulmonary edema from thoracic radiographs, using an American College of Veterinary Radiology-certified veterinary radiologist's interpretation as the reference standard. Five hundred consecutive canine thoracic radiographs made after-hours by a veterinary Emergency Department were retrieved. A total of 481 of 500 cases were technically analyzable. Based on the radiologist's assessment, 46 (10.4%) of these 481 dogs were diagnosed with cardiogenic pulmonary edema (CPE+). Of these cases, the AI software designated 42 of 46 as CPE+ and four of 46 as cardiogenic pulmonary edema negative (CPE-). Accuracy, sensitivity, and specificity of the AI-based software compared to radiologist diagnosis were 92.3%, 91.3%, and 92.4%, respectively (positive predictive value, 56%; negative predictive value, 99%). Findings supported using AI software screening for thoracic radiographs of dogs with suspected cardiogenic pulmonary edema to assist with short-term decision-making when a radiologist is unavailable.

This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF-α and IL-6 levels in serum and lung tissues were measured. The results indicated that RIPC could attenuate ALI in sepsis. miR-142-5p expression was increased in serum, lung tissues, and serum-derived EVs of ALI rats following RIPC. miR-142-5p could target PTEN to activate the PI3K/Akt signaling pathway. miR-142-5p shuttled by serum-derived EVs reduced pulmonary edema, neutrophil infiltration, and TNF-α and IL-6 levels, thus alleviating ALI in LPS-induced septic rats upon RIPC. Collectively, serum-derived EVs-loaded miR-142-5p downregulated PTEN and activated PI3K/Akt to inhibit ALI in sepsis following RIPC, thus highlighting potential therapeutic molecular targets against ALI in sepsis.

Severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is the seventh member of the coronaviruses (CoVs) family that infects humans and causes coronavirus disease 2019 (COVID-19), which is currently a global pandemic. Widespread secretion of cytokines has been shown to occur early in severe cases of the disease and can be an effective factor in the rapid progression of the disease. The storm of cytokines including interleukin (IL)-1β, IL-2, IL-7, IL-6, IL-8, IL-10, IL-17, and gamma interferon (INF-ɣ) has been reported in several organ failures. Systemic inflammation indicates an advanced stage of acute disease, which is characterized by multiple organ failure and elevated key inflammatory markers. The important disturbances in the various body systems such as alveolar damage and pulmonary edema in the lung, increase of liver enzymes in the liver, decrease of microbiota and increase of mesenteric edema in the gastrointestinal system, increase of blood urea nitrogen (BUN), creatinine (Cr) and glomerular filtration rate (GFR) in the kidney, myocardial dysfunction, arrhythmia and cardiac enzymes elevation in the heart, blood brain barrier (BBB) disruption, brain edema and encephalopathy in the brain have been reported. Studies have shown a gender difference between the incidence and mortality of COVID-19. In this review, we investigated the gender difference in the systemic effects of COVID-19 and found that this gender difference exists especially in the respiratory, cardiovascular, liver, gastrointestinal and kidney systems. Due to the worse outcome of COVID in males, the role of female sex hormones in causing these gender differences is noticeable. There can be a systemic and local effect of female sex hormones, especially estrogen and possibly progesterone, on various cells. Among the effects of these hormones is the regulation of localized angiotensin-converting enzyme 2 (ACE2) levels. ACE2 is the route of entry for SARS-CoV-2 virus into the cell. It is hoped that this review would address gender differences for better management of COVID-19 treatment.

Re-expansion Pulmonary oedema (RPE) is a rare but potentially fatal complication, which can arise after a rapid decompressive treatment of pulmonary collapse secondary to pleural effusion, pneumothorax or atelectasis. The pathophysiological mechanism is still poorly understood, admitting a

Sympathetic crash acute pulmonary edema (SCAPE) is a life-threatening injury, which requires early recognition and intervention to prevent mortality. We present a case of 18-year-old woman with no previous comorbidity, presenting with SCAPE who was successfully resuscitated and eventually diagnosed with renal artery stenosis. Pickering syndrome is a rare cause of hypertensive emergency and should be considered in a young patient presenting with SCAPE in emergency department.

Background: Chest X-ray is a practical tool to semi-qualify pulmonary congestion. Remote dielectric sensing (ReDS) is a recently introduced, non-invasive, electromagnetic energy-based technology to quantify pulmonary congestion without expert technique. We compared these two modalities to clarify appropriate clinical situations for each modality. Methods: ReDS and chest X-ray measurements were prospectively performed on admission in consecutive hospitalized patients with cardiovascular diseases. In the chest X-ray, the congestive score index (CSI) was calculated blindly by two independent experts and averaged. CSIs were correlated with ReDS values. Results: A total of 458 patients (76 (69, 82) years old, 267 men, and 130 heart failure) were included. Median ReDS value was 28% (25%, 33%). There was a mild correlation between ReDS values and CSIs (r = 0.329, p < 0.001). The correlation between ReDS values and CSIs became stronger in the heart failure cohort (r = 0.538, p < 0.001). In patients with mild congestion (ReDS < 35%), ReDS values, instead of CSI, stratified the degree of congestion. In patients with severe congestion (ReDS > 35%), both modalities stratified the degree of congestion. Conclusions: Both chest X-ray and ReDS are useful for assessing severe pulmonary congestion, whereas ReDS would be preferred to chest X-ray in stratifying the severity of mild pulmonary congestion.

One of the most dreaded complications of end stage liver disease is hepatorenal syndrome AKI (HRS-AKI; formally known as hepatorenal syndrome 1 [HRS-1]). HRS-AKI carries a high mortality, and treatment options are limited. Guidelines recommend terlipressin as the first-line treatment of HRS-AKI

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.

Purpose : To compare the density of the whole human lungs between freshwater drowning cases (FWDC) and saltwater drowning cases (SWDC) by using three-dimensional data obtained via postmortem computed tomography (PMCT). Materials and methods : Of 278 drowning cases in our database, 37 cases (18 men, 19 women ; mean age 70.8 y ; range 43-95 y) were selected for the study. Twenty-five were FWDC and 12 were SWDC. Three-dimensional data of the bilateral lungs were obtained from the PMCT. The mean, standard deviation, maximum, and minimum values of the CT number of the whole lungs were calculated. The mean CT numbers of lungs in FWDC and SWDC were compared. Unpaired t-tests were used to analyze the data. A P value of < 0.05 was considered statistically significant. Results : The mean (±SD) CT number of whole lungs was higher in the SWDC group than that in the FWDC group (−522.87 ± 66.80 Hounsfield Unit [HU], and −616.40 ± 86.34 HU, respectively, P = 0.001). Conclusion : Based on the PMCT findings, a higher lung density was observed in individuals who drowned in saltwater than those in freshwater, which may reflect the differences in the condition of the interstitial edema in the two types of drowning.