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Danish Medical Journal Jun 2024Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute...
INTRODUCTION
Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs.
METHODS
This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis.
CONCLUSIONS
This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide.
FUNDING
Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation.
TRIAL REGISTRATION
This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).
Topics: Furosemide; Humans; Heart Failure; Prospective Studies; Pulmonary Edema; Diuretics; Acute Disease; Remote Sensing Technology; Female; Male; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 38903022
DOI: 10.61409/A11230697 -
Nature Reviews. Disease Primers Jun 2024Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude... (Review)
Review
Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.
Topics: Humans; Altitude Sickness; Altitude; Acclimatization; Brain Edema; Pulmonary Edema; Hypertension, Pulmonary; Hypoxia
PubMed: 38902312
DOI: 10.1038/s41572-024-00526-w -
Frontiers in Pharmacology 2024Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of... (Review)
Review
BACKGROUND AND OBJECTIVES
Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS.
METHODS
Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed.
RESULTS
We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism.
CONCLUSION
The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.
PubMed: 38895636
DOI: 10.3389/fphar.2024.1393209 -
Journal of Inflammation Research 2024Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the...
BACKGROUND
Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin's effects and functions in a young mouse model of sepsis-induced ALI.
METHODS
Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin-eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1β, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1β, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1β and S100A8/A9 by Western blot.
RESULTS
The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1β, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC.
CONCLUSION
Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1β pathway.
PubMed: 38895139
DOI: 10.2147/JIR.S460413 -
International Immunopharmacology Jun 2024Monomethyl fumarate (MMF), a potent anti-inflammatory agent used to treat multiple sclerosis, has demonstrated efficacy in various inflammatory and ischemia/reperfusion...
Monomethyl fumarate (MMF), a potent anti-inflammatory agent used to treat multiple sclerosis, has demonstrated efficacy in various inflammatory and ischemia/reperfusion (IR) models; however, its impact on IR-induced acute lung injury (ALI) has not been explored. We investigated, for the first time, whether MMF attenuates lung IR injury through inhibition of the GAPDH/Siah1 signaling pathway. Rats were subjected to IR injury using an isolated perfused lung model, and proximity ligation assays were employed to evaluate the presence and distribution of the GAPDH/Siah1 complex. In vitro studies involved pretreating human primary alveolar epithelial cells (HPAECs) with MMF and/or inducing GAPDH overexpression or silencing, followed by exposure to hypoxia-reoxygenation. The findings revealed significantly reduced lung damage indicators, including edema, proinflammatory cytokines, oxidative stress and apoptosis, in MMF-treated rats. Notably, MMF treatment inhibited GAPDH/Siah1 complex formation and nuclear translocation, indicating that disruption of the GAPDH/Siah1 cascade was the primary cause of these improvements. Our in vitro studies on pretreated HPAECs corroborate these in vivo findings, further strengthening this interpretation. Our study results suggest that the protective effects of MMF against lung IR injury may be attributed, at least in part, to its ability to disrupt the GAPDH/Siah1 signaling cascade, thereby attenuating inflammatory and apoptotic responses. Given these encouraging results, MMF has emerged as a promising therapeutic candidate for the management of lung IR injury.
PubMed: 38889510
DOI: 10.1016/j.intimp.2024.112488 -
Journal of Inflammation Research 2024Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading to scattered... (Review)
Review
Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading to scattered interstitial alterations, pulmonary edema, and subsequent acute hypoxic respiratory insufficiency. Acute lung injury (ALI), along with its more serious counterpart, acute respiratory distress syndrome (ARDS), carry a fatality rate that hovers around 30-40%. Its principal pathological characteristic lies in the unchecked inflammatory reaction. Currently, the main strategies for treating ALI are alleviation of inflammation and prevention of respiratory failure. Concerning the etiology of ALI, NLRP3 Inflammasome is essential to the body's innate immune response. The composition of this inflammasome complex includes NLRP3, the pyroptosis mediator ASC, and pro-caspase-1. Recent research has reported that the inflammatory response centered on NLRP3 inflammasomes plays a key part in inflammation in ALI, and may hence be a prospective candidate for therapeutic intervention. In the review, we present an overview of the ailment characteristics of acute lung injury along with the constitution and operation of the NLRP3 inflammasome within this framework. We also explore therapeutic strategies targeting the NLRP3 inflammasome to combat acute lung injury.
PubMed: 38887753
DOI: 10.2147/JIR.S464838 -
Cureus May 2024We present a case report of a patient with infective endocarditis. He came to the emergency room with respiratory failure due to severe pneumonia and pulmonary edema. On...
We present a case report of a patient with infective endocarditis. He came to the emergency room with respiratory failure due to severe pneumonia and pulmonary edema. On 2D transesophageal echocardiography, vegetations were seen in both mitral and aortic valves, with mitral valve perforation and severe regurgitation. His clinical presentation and severity of the disease made him suitable for urgent valve repair. He was submitted to mitral valvuloplasty with closure of the valve perforation and insertion of a bioprosthetic aortic valve. Despite significant clinical improvement, a post-surgical complication was noted with new-onset lung injury after cardiopulmonary bypass. This is an interesting case of a patient with suspected retrograde valve involvement, affecting the aortic valve, the mitral-aortic intervalvular fibrosa, and the mitral valve, ending with mitral valve abscess with leaflet perforation and valvular regurgitation.
PubMed: 38887336
DOI: 10.7759/cureus.60515 -
Two-component regulatory system TCS08 of a serotype 4 strain in pneumococcal pneumonia pathogenesis.Journal of Oral Biosciences Jun 2024Streptococcus pneumoniae, a human respiratory pathogen, causes diseases with severe morbidity and mortality rates worldwide. The two-component regulatory system (TCS) is...
OBJECTIVES
Streptococcus pneumoniae, a human respiratory pathogen, causes diseases with severe morbidity and mortality rates worldwide. The two-component regulatory system (TCS) is an important signaling pathway that enables regulation of gene expression in response to environmental cues, thereby allowing an organism to adapt to a variety of host niches. Here we examined the contribution of pneumococcal TCS08 to bacterial colonization, the development of pneumonia, and pulmonary dysfunction.
METHODS
We employed an hk08 knockout mutant (Δhk08) with a background of the TIGR4 wild-type (WT) strain to verify whether TCS08 is associated with bacterial colonization and the development of pneumonia in a murine infection model. To clarify the association of hk08 inactivation-induced phenotypic changes with their virulence, we examined pneumococcal capsule production, colony morphology, and surface-displayed protein profiles.
RESULTS
Pneumococcal TCS08 was involved in bacterial colonization in the respiratory tract. Interruption of the signaling pathway of TCS08 by hk08 inactivation impaired mouse survival and increased the bacterial burden within the respiratory tract. Furthermore, a histopathological examination revealed massive inflammatory cell infiltration, edema formation, and diffuse alveolar damage in the lung tissues of mice infected with Δhk08 versus the WT or complemented strain. Interestingly, virulence-associated phenotype changes, including capsule production, increased chain length, and surface-displayed protein profile, were observed in the Δhk08 strain.
CONCLUSIONS
The present findings indicate that TCS08 contributes to pneumococcal colonization and pulmonary dysfunction by assisting adaptation to the respiratory tract milieu, leading to the development of pneumonia.
PubMed: 38885903
DOI: 10.1016/j.job.2024.06.001 -
Advances in Experimental Medicine and... 2024Total anomalous pulmonary venous return (TAPVR) is rare (accounting for about 1% of all CHD) and can occur as a single lesion or in combination with other types of CHD... (Review)
Review
Total anomalous pulmonary venous return (TAPVR) is rare (accounting for about 1% of all CHD) and can occur as a single lesion or in combination with other types of CHD (such as heterotaxy or HLHS). TAPVR is defined as an abnormal connection where all pulmonary veins do not drain into the left atrium but into the right atrium either directly or through a vein that is connected to the right atrium. TAPVR can be divided into four anatomic groups (Fig. 32.1): (1) supracardiac (about 55%), (2) cardiac (about 30%), (3) infracardiac (about 13%), and (4) mixed (very rare). In addition, it can be divided into two physiological types: nonobstructed and obstructed. Embryologically, all pulmonary veins usually connect to a pulmonary venous confluence that connects to the left atrium. If this connection does not occur, the pulmonary venous confluence connects to a systemic vein instead.
Topics: Humans; Scimitar Syndrome; Pulmonary Veins; Heart Atria
PubMed: 38884734
DOI: 10.1007/978-3-031-44087-8_32 -
Journal of Thoracic Disease May 2024With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic...
BACKGROUND
With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a "biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital.
METHODS
Patients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively.
RESULTS
We evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 [interquartile range (IQR), 1-4] hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks.
CONCLUSIONS
MT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.
PubMed: 38883638
DOI: 10.21037/jtd-24-219