Noncardiogenic Edema Research Articles

Ischemic Postconditioning Mitigates Lipopolysaccharide-induced Acute Lung Injury in Rats.

Acute lung injury (ALI) is a syndrome characterized by the disruption of alveolar endothelial and epithelial barriers, neutrophilic infiltration in pulmonary regions, and non-cardiogenic edema, associated with high mortality and morbidity. Despite intensive research efforts, there is currently no approved specific treatment for the condition. The aim of this study was to investigate the potential beneficial effect of ischemic post-conditioning in lipopolysaccharide (LPS)-induced lung injury and its possible association with inflammatory and apoptotic processes. Lung injury was induced in rats by a single intraperitoneal administration of 10 mg/kg LPS. Under anesthesia, latex tourniquets were wrapped around both hind limbs of the animals in a region close to the body to achieve complete ischemia. The ischemic conditioning procedure consisted of four cycles of 10 min of ischemia followed by 10 min of reperfusion. Inflammation, and apoptosis levels were measured using ELISA. Hematoxylin and eosin staining was used for histopathological evaluation, while TUNEL staining was employed for apoptotic cell counting. One-way analysis of variance (ANOVA) with post hoc Tukey test was used for comparisons between groups. Intraperitoneal LPS administration induced neutrophil infiltration and apoptotic cell death in lung tissue. These effects were prevented by remote ischemic postconditioning (RIPostC) application. Additionally, the beneficial effects of ischemic conditioning can be transferred via serum. RIPostC can ameliorate LPS-induced ALI. The mechanism of the protective effects of RIPostC may lie in the suppression of apoptosis and neutrophil infiltration.

Radiological Evaluation of Various Complications of Dengue Hemorrhagic Fever

Abstract: Objective: This retrospective study aimed to investigate the spectrum of imaging findings in patients with Dengue Hemorrhagic Fever (DHF) and explore the associated clinical parameters. Methods: A total of 237 patients diagnosed with DHF confirmed via ELISA were included in the study. Imaging modalities including abdominal and chest ultrasound in every patient, HRCT (n=19), and CT brain scans (n=3)in patients having symptoms related to chest or brain were performed as part of the diagnostic workup. Demographic data, platelet counts, DHF grading, and imaging findings were recorded. Descriptive analysis was conducted using SPSS v26. Results: The mean age of the patients was 34.50 ± 16.4, with a male preponderance (58.2%). Grade I DHF was observed in 69.2% of patients, followed by Grade II (23.6%) and Grade III (7.1%). Abdominal ultrasound revealed hepatomegaly (19.4%) and splenomegaly (19.6%). Thick-walled gall bladder (34.7%), pericholecystic fluid (7.1%), and gall bladder sludge (5.06%) were also noted. Ascites was present in 19% of cases. Chest ultrasound detected pleural effusion in 11.8% of patients, predominantly mild. HRCT scans showed pleural effusion (89.5%), ground glass opacities and consolidations (36.8%), alveolar shadowing (26.3%), and signs of non-cardiogenic edema (10.5%). CT brain scans revealed intracerebral bleed in 2 out of 3 patients with neurological manifestations. Conclusion: This study provides insights into the spectrum of imaging findings in DHF. Abdominal ultrasound demonstrated hepatomegaly, splenomegaly, and gall bladder abnormalities, while chest ultrasound and HRCT revealed pleural effusion and pulmonary manifestations. CT brain scans identified intracerebral bleeding in some cases. These findings highlight the importance of imaging modalities in evaluating DHF complications and guiding appropriate management. Prospective studies with larger sample sizes are warranted to validate these findings and further enhance our understanding of imaging features in DHF.

Targeting BRD4 with PROTAC degrader ameliorates LPS-induced acute lung injury by inhibiting M1 alveolar macrophage polarization

ObjectivesAcute lung injury (ALI) is a highly inflammatory condition with the involvement of M1 alveolar macrophages (AMs) polarization, eventually leading to the development of non-cardiogenic edema in alveolar and interstitial regions, accompanied by persistent hypoxemia. Given the significant mortality rate associated with ALI, it is imperative to investigate the underlying mechanisms of this condition so as to identify potential therapeutic targets. The therapeutic effects of the inhibition of bromodomain containing protein 4 (BRD4), an epigenetic reader, has been proven with high efficacy in ameliorating various inflammatory diseases through mediating immune cell activation. However, little is known about the therapeutic potential of BRD4 degradation in acute lung injury. MethodsThis study aimed to assess the protective efficacy of ARV-825, a novel BRD4-targeted proteolysis targeting chimera (PROTAC), against ALI through histopathological examination in lung tissues and biochemical analysis in bronchoalveolar lavage fluid (BALF). Additionally, the underlying mechanism by which BRD4 regulated M1 AMs was elucidated by using CUT & Tag assay. ResultsIn this study, we found the upregulation of BRD4 in a lipopolysaccharide (LPS)-induced ALI model. Furthermore, we observed that intraperitoneal administration of ARV-825, significantly alleviated LPS-induced pulmonary pathological changes and inflammatory responses. These effects were accompanied by the suppression of M1 AMs. In addition, our findings revealed that the administration of ARV-825 effectively suppressed M1 AMs by inhibiting the expression of IRF7, a crucial transcriptional factor involved in M1 macrophages. ConclusionOur study suggested that targeting BRD4 using ARV-825 is a potential therapeutic approach for ALI.

Increasing Awareness of Naloxone-Induced Noncardiogenic Pulmonary and Peripheral Edema

AbstractIntroductionNaloxone use has increased in recent years in response to the nation’s opioid crisis. Once only available to health care professionals, it is now obtainable by prescription for persons at risk for substance overdose and their families. Increasing its availability is seen by some as an “over-the-counter solution” to the opioid problem. However, while naloxone has been viewed as relatively safe, with a low side effect profile when appropriately dosed and monitored, it is not without safety concerns that may go unrecognized or misattributed to other causes.MethodsHere we present a case study of a 41-year-old female who presented to our medication-assisted treatment (MAT) clinic complaining of sudden onset weight gain, shortness of breath, upper and lower extremity peripheral edema, tachycardia, insomnia, and nocturnal enuresis. These symptoms made it difficult for her to work at her housekeeping job, resulting in missed workdays. She had seen a primary care provider for her symptoms and been prescribed a rescue inhaler for her shortness of breath. This patient had previously been treated for opioid use disorder with buprenorphine/naloxone and experienced similar symptoms, which disappeared when she relapsed on opioids. However, symptoms reappeared upon resuming her prescribed treatment.ResultsThe patient was identified as experiencing side effects to naloxone, causing noncardiogenic edema. Her MAT medication was switched to buprenorphine. Within two weeks her heart rate had returned to normal, she had lost weight, and she no longer had nocturnal enuresis or needed the rescue inhaler. Her peripheral edema resolved so she was able to walk better and resume work. At the same time, buprenorphine continued to relieve her cravings.There is a dearth of information related to naloxone-induced edema. Our patient had not received a formal evaluation of pulmonary edema, but her pulmonary and cardiac symptoms were consistent with that diagnosis. Although pulmonary edema is mentioned in the product literature, peripheral edema is not. A literature search indicates that the number of case studies on naloxone-induced pulmonary edema have increased since 2018, but only one other case of naloxone-induced peripheral edema was discovered.Conclusions/ImportanceNaloxone is used in a variety of settings by differing types of health care providers. As the number of persons treated with naloxone increases, there will likely be a corresponding increase in incidences of pulmonary and/or peripheral edema as side effects. Providers and patients who are not aware of these manifestations and their relationship to naloxone treatment may easily attribute presenting symptoms to cardiogenic or other causes, as this case illustrates. It is important for providers in all settings to consider new onset shortness of breath and edema within the context of the person’s whole health and to be aware of their implications for mental as well as physical health.FundingNo Funding

Computational pulmonary edema: A microvascular model of alveolar capillary and interstitial flow.

We present a microvascular model of fluid transport in the alveolar septa related to pulmonary edema. It consists of a two-dimensional capillary sheet coursing by several alveoli. The alveolar epithelial membrane runs parallel to the capillary endothelial membrane with an interstitial layer in between, making one long septal tract. A coupled system of equations is derived using lubrication theory for the capillary blood, Darcy flow for the porous media of the interstitium, a passive alveolus, and the Starling equation at both membranes. Case examples include normal physiology, cardiogenic pulmonary edema, noncardiogenic edema Acute Respiratory Distress Syndrome (ARDS) and hypoalbuminemia, and the effects of positive end expiratory pressure. COVID-19 has dramatically increased ARDS in the world population, raising the urgency for such a model to create an analytical framework. Under normal conditions, the fluid exits the alveolus, crosses the interstitium, and enters the capillary. For edema, this crossflow is reversed with the fluid leaving the capillary and entering the alveolus. Because both the interstitial and capillary pressures decrease downstream, the reversal can occur within a single septal tract, with edema upstream and clearance downstream. Overall, the interstitial pressures are found to be significantly more positive than values used in the traditional physiological literature that creates steep gradients near the upstream and downstream end outlets, driving significant flows toward the distant lymphatics. This new physiological flow may provide a possible explanation to the puzzle, noted since 1896, of how pulmonary lymphatics can function so far from the alveoli: the interstitium can be self-clearing.

Gabapentinoid-induced peripheral edema and acute heart failure: A translational approach combining a nationwide pharmacovigilance study with preclinical experimental data

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure of unknown clinical and pathophysiological characteristics. Characterize the onset patterns of gabapentinoid-induced peripheral edema and investigate the pharmacological mechanisms. All cases of peripheral edema or heart failure [MedDRA Hight-Level Term ‘total volume fluid increased’ or High-Level Group Term ‘heart failures’] involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were considered to describe their onset patterns (e.g., time to onset, patient comorbidities). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries (Halpern's arteriography) and on the electrophysiological properties of rat ventricular cardiomyocytes (whole-cell voltage-clamp). A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57–85, range 32–95). The median time to onset were 23 days (IQR 10–54) and 17 days (IQR 3–30) for non-cardiogenic edema and acute heart failure, respectively. Whatever the type of peripheral edema, the main patient comorbidity was hypertension (17/50, 34%), they frequently occurred after a dose escalation (27/45, 60%) and the evolution was rapidly favorable after gabapentinoid discontinuation (median 7 days, IQR 5–13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. While the pharmacological substrate of gabapentinoid-induced cardiac decompensation deserves further investigations, the primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade. Clinicians should be alert to this risk and to the management of gabapentinoid-induced peripheral edema in order to limit any risk of prescribing cascade with diuretics.

Gabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments

IntroductionGabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac. Objectives & methodsAll cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between January 1, 1994 and April 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiological properties of rat ventricular cardiomyocytes. ResultsA total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57–85, range 32–95). The median time to onset were 23 days (IQR 10–54) and 17 days (IQR 3–30) for non-cardiogenic edema and acute heart failure, respectively. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5–13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. ConclusionGabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade under the experimental conditions tested.

Kidney-Pulmonary Crosstalk from Pathophysiological Perspective

Lungs and kidneys are distant organs which are functionally related in physiological and pathological contexts. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are common complications in acute kidney injury (AKI) or acute-on-chronic kidney disease. On the other hand, there is a considerable risk of AKI in respiratory diseases such as ARDS and chronic obstructive pulmonary disease (COPD). From a pathophysiological point of view, the kidney-lung crosstalk involves interdependency in the regulation of fluid hemodynamic, acid-base and electrolyte balance, and carbon dioxide partial pressure. Aside from the closely related function, the crosstalk may also occur by non-classical mechanisms such as through activation of systemic inflammation, excessive cytokine release, and the formation of auto-antibody which targets both kidneys and lungs. This review discussed several disease mechanisms by which kidney and lungs affect each other or are simultaneously affected by pathological processes. Particularly, this review discussed some specific mechanisms in lungs and kidneys, such as how hypoxemia and hypercapnia induced by ARDS may reduce kidney function and how distance injury on kidney may affect the development of non-cardiogenic edema lungs.

Pulmonary Edema II: Noncardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome [ARDS]). This review focuses on noncardiogenic pulmonary edema and describes the general approach to patients with suspected pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of noncardiogenic pulmonary edema are reviewed. Miscellaneous causes of pulmonary edema are discussed, including neurologic insults, exposure to high altitude, reexpansion of a collapsed lung, lung transplantation, upper airway obstruction, drugs, and lung resection. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with noncardiogenic pulmonary edema, the definition of ARDS, causes of ARDS, and treatments for ARDS that do not involve ventilation. This review contains 3 figures, 9 tables, and 55 references. Key words: acute respiratory distress syndrome, diffuse alveolar damage, noncardiogenic pulmonary edema, pulmonary edema

Pulmonary Edema II: Noncardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome [ARDS]). This review focuses on noncardiogenic pulmonary edema and describes the general approach to patients with suspected pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of noncardiogenic pulmonary edema are reviewed. Miscellaneous causes of pulmonary edema are discussed, including neurologic insults, exposure to high altitude, reexpansion of a collapsed lung, lung transplantation, upper airway obstruction, drugs, and lung resection. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with noncardiogenic pulmonary edema, the definition of ARDS, causes of ARDS, and treatments for ARDS that do not involve ventilation. This review contains 3 figures, 9 tables, and 55 references. Key words: acute respiratory distress syndrome, diffuse alveolar damage, noncardiogenic pulmonary edema, pulmonary edema

Pulmonary Edema I: Cardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options. This review contains 3 figures, 4 tables, and 29 references Keywords: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law

Pulmonary Edema I: Cardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options. This review contains 3 figures, 4 tables, and 24 references. Key words: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law

Pulmonary Edema I: Cardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options. This review contains 3 figures, 4 tables, and 24 references. Key words: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law

DIFFUSE ALVEOLAR DAMAGE COMPLICATING ELECTROCONVULSIVE THERAPY

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Electroconvulsive therapy (ECT) has been increasingly used over the last few years for various indications, of the rare complications described in the literature is pulmonary edema, only 9 case reports described this complication, 8 of which were attributed to none cardiogenic cause and one had a cardiology component. Here we present a case of pulmonary edema and diffuse alveolar damage (DAD) with hemorrhage with no cardiac component CASE PRESENTATION: 41 years old female smoker, known to have fibromyalgia, systemic lupus erythematosus (SLE) in remission for years, diabetes and severe bipolar disorder refractory to medical therapy' Patient were admitted to the hospital for ECT, shortly after the procedure she developed hemoptysis and shortness of breath requiring oxygen therapy, chest tomography ruled out pulmonary embolism but showed evidence of diffuse alveolar process with ground glass pacification (Image 2). no inhaled medications were used in anesthesia and other inhalational injuries ruled out by history, also vasculitis and infectious process were ruled out. bronchoscopy suggestive of DAD with hemorrhage (Image 1). review of the patient's anesthesia report showed no variation in vital signs during the procedure and ECHO was within normal. the patient recovered with supportive care and advised to be intubated on subsequent sessions DISCUSSION: None cardiogenic pulmonary edema has been described as a complication of ECT, while most cases describe it as a subsequence of variation in blood pressure during the procedure few described it as a result of pressure variation. The theory used to explain the development of pulmonary edema / diffuse alveolar damage is explained as the partially paralyzed diaphragm (Paralytic in smaller dose are used that doesn't result in complete paralysis of the diaphragm as the procedure is aimed to be short with minimal sedation) contract against a close epiglottis with abducted vocal cords from the ECT current. This will result in negative pressure inside the chest cavity and the development of shearing force resulting in damage of the small blood vessels and extravasation of blood and plasma into the alveolar space, which was the case in our patient. Other contributory causes were ruled out. recurrence is not common but precautions in subsequent sessions are warranted. the development of noncardiogenic edema is not a contraindication for further sessions. CONCLUSIONS: ECT is being widely used as a new modality for therapy for refractory psychiatric diseases, precautions to the possible complications are warranted, shortness of breath or hemoptysis post the procedure should raise the suspension of noncardiogenic pulmonary edema / diffuse alveolar damage. treatment is supportive with diuretics being the first line. no other therapies have been described. this complication warranted precautions in the following sessions but doesn't contraindicate them. REFERENCE #1: Manne JR, Kasirye Y, Epperla N, Garcia-Montilla RJ. Non-cardiogenic pulmonary edema complicating electroconvulsive therapy: a short review of the pathophysiology and diagnostic approach. Clin Med Res. 2012 Aug;10(3) 131-136. doi:10.3121/cmr.2011.1030. PMID: 22031475; PMCID: PMC3421372. REFERENCE #2: Hatta K, Kitajima A, Ito M, Usui C, Arai H. Pulmonary edema after electroconvulsive therapy in a patient treated for long-standing asthma with a beta2 stimulant. J ECT. 2007 Mar;23(1) 26-27. doi:10.1097/01.yct.0000263258.52162.63. PMID: 17435570. REFERENCE #3: Myers, Christopher & Gopalka, Ajay & Glick, David & Goldman, Morris & Dinwiddie, Stephen. (2008). A Case of Negative-Pressure Pulmonary Edema After Electroconvulsive Therapy. The journal of ECT. 23. 281-3. 10.1097/yct.0b013e3180de5d44. DISCLOSURES: No relevant relationships by Amro Alastal, source=Web Response No relevant relationships by Rami Batarseh, source=Web Response No relevant relationships by Christopher Lipinski, source=Web Response

Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies.

Vaccinations are widely credited with reducing death rates from COVID-19, but the underlying host-viral mechanisms/interactions for morbidity and mortality of SARS-CoV-2 infection remain poorly understood. Acute respiratory distress syndrome (ARDS) describes the severe lung injury, which is pathologically associated with alveolar damage, inflammation, non-cardiogenic edema, and hyaline membrane formation. Because proteostatic pathways play central roles in cellular protection, immune modulation, protein degradation, and tissue repair, we examined the pathological features for the unfolded protein response (UPR) using the surrogate biomarker glucose-regulated protein 78 (GRP78) and co-receptor for SARS-CoV-2. At autopsy, immunostaining of COVID-19 lungs showed highly elevated expression of GRP78 in both pneumocytes and macrophages compared with that of non-COVID control lungs. GRP78 expression was detected in both SARS-CoV-2-infected and un-infected pneumocytes as determined by multiplexed immunostaining for nucleocapsid protein. In macrophages, immunohistochemical staining for GRP78 from deceased COVID-19 patients was increased but overlapped with GRP78 expression taken from surgical resections of non-COVID-19 controls. In contrast, the robust in situ GRP78 immunostaining of pneumocytes from COVID-19 autopsies exhibited no overlap and was independent of age, race/ethnicity, and gender compared with that from non-COVID-19 controls. Our findings bring new insights for stress-response pathways involving the proteostatic network implicated for host resilience and suggest that targeting of GRP78 expression with existing therapeutics might afford an alternative therapeutic strategy to modulate host-viral interactions during SARS-CoV-2 infections.

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

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

Analysis of the Efficacy and Mechanism of Action of Xuebijing Injection on ARDS Using Meta-Analysis and Network Pharmacology.

Objective Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing. Methods We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF-α and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF-α and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software. Results Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54–0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97–-4.06)), reduced the TNF-α ((MD), -1.23 (95% CrI, -1.38–-1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52–-0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing's action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-α, and two components docked with IL-6 got the binding energies lower than -5. Conclusion Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF-α is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.

Veno-Venous Extracorporeal Membrane Oxygenation - Rapid Recovery for Post-Surgical Negative Pressure Pulmonary Edema

Introduction Postoperative pulmonary edema can be cardiogenic, non-cardiogenic or a combination of both. A major cause of noncardiogenic edema is negative pressure pulmonary edema (NPPE) due to inspiration against a closed glottis. Within minutes, patients can develop dyspnea and pink tinged frothy sputum. Risk factors include a short neck, obstructive sleep apnea, and previous ENT surgeries. There have also been a few case reports that demonstrate NPPE after the use of sevoflurane. Below we present a case of a young female who developed post-surgical NPPE which was managed with short-term veno-venous extracorporeal membrane oxygenation (V-V ECMO). Case Report A 30-year-old female with minimal past medical history was airlifted to the cardiovascular intensive care unit four hours after a condyloma removal under sevoflurane anesthesia with a laryngeal mask airway. The patient developed post-operative hypoxia and hemoptysis requiring intubation. A computerized tomography (CT) scan of the chest with contrast revealed ground-glass opacities concerning for diffuse alveolar hemorrhage (DAH). Upon arrival, a bronchoscopy with sequential lavages revealed persistently sanguineous fluid which pointed away from active alveolar hemorrhage. The ECMO team was consulted due to concerns for acute lung injury. Given the preserved cardiac function, the patient was placed on V-V ECMO for two days with rapid recovery of lung function. The patient was maintained on ventilator support for two additional days before being discharged on the fifth day. Summary The mainstay of treatment for NPPE is supportive care. Most patients require prolonged monitoring in the postanesthesia care unit and usually recover within a few hours with supplemental oxygen and continuous positive end-expiratory pressure. Occasionally, patients will need to be intubated. In this case, the post-procedural CT scan showed no signs of cardiogenic pulmonary edema, but rather DAH. Given ventilation difficulties with adequate cardiac function, the patient was an appropriate candidate for V-V ECMO. The DAH could possibly be due to sevoflurane but was more likely a consequence of NPPE. Regardless of the cause, the use of V-V ECMO is highly effective in allowing patients to rapidly recover respiratory function without long-term complications.

Long Non-coding RNA LINC-PINT and LINC00599 Polymorphisms are Associated With High-altitude Pulmonary Edema in Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility. MethodsThis study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. ResultsWe observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR=0.65, 95% CI=0.43–0.98, p=0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p=0.006; recessive model: p=0.005 additive model: p=0.018; and allele model: p=0.012; rs72625676, codominant model: p=0.038; recessive model: p=0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p=0.049; recessive model: p=0.029; rs1962430: genotype model: p=0.024; recessive model: p=0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p=0.018). ConclusionOur study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.

Non-Cardiogenic Pulmonary Edema With Refractory Hypotension in a Child From Amlodipine Overdoses

Intoxications from calcium blockers are not common in daily pediatric practice, but often they can be life-threatening and result fatal for children. Non-cardiogenic edema in children as a result of overdose from amlodipine is rare. In this article, we want to present a case of an intentional intoxication from overdose of amlodipine in a teen girl who suffered complications with refractory hypotension and non-cardiogenic pulmonary edema after 2 days from ingestion. This article wants to highlight the reporting of this rare life-threatening complication because of overdose. It will also focus on the successful supportive treatment with liquids, salt of calcium, vasopressors, glucagon, intra-lipids, mechanical ventilation and the superiority of using high-dose insulin-euglycemia in the concomitant refractory hypotension. Int J Clin Pediatr. 2020;9(4):120-124 doi: https://doi.org/10.14740/ijcp398