Capillary Leak Research Articles

Systemic capillary leak syndrome.

The vascular endothelial barrier maintains intravascular volume and metabolic homeostasis. Although plasma fluids and proteins extravasate continuously from tissue microvasculature (capillaries, post-capillary venules), systemic vascular leakage increases in critical illness associated with sepsis, burns and trauma, among others, or in association with certain drugs or toxin exposures. Systemically dysregulated fluid homeostasis, which can lead to hypovolaemia, hypotensive shock and widespread tissue oedema, has been termed systemic capillary leak syndrome (SCLS) when overt secondary causes (for example, heart or liver failure) are excluded. In severe forms, SCLS is complicated by compartment syndrome in the extremities and multi-organ dysfunction syndrome due to shock and systemic hypoperfusion. The different forms of SCLS include idiopathic SCLS (ISCLS) and secondary SCLS(SSCLS), which can be triggered by several conditions, including certain infections and haematological malignancies. A subgroup of patients with ISCLS have monoclonal gammopathy-associated SCLS (also known as Clarkson disease), which is an ultra-rare and extreme form of ISCLS. ISCLS can be managed effectively with monthly prophylactic immunoglobulin therapy whereas SSCLS frequently does not recur once the underlying condition resolves or the offending agent is discontinued. Thus, differentiation between ISCLS, SSCLS and other causes of oedema is crucial for quick diagnosis and positive patient outcomes.

Systemic capillary leak syndrome.

Systemic capillary leak syndrome.

Dengue fever with atypical manifestations in a child with beta thalassemia major post splenectomy

Dengue is one of the significant public health concerns in endemic countries. With plasma leakage as the primary pathophysiology in the process of severe dengue infection with hemoconcentration and thrombocytopenia being the significant laboratory diagnostic features in children, the presentation in children with underlying hemato-oncological conditions is atypical and often, anemia is found in these children, instead of hemoconcentration. We describe a young boy with beta thalassemia major who underwent splenectomy for hypersplenism 5-months ago with dengue illness, characterized by features mimicking a severe post splenectomy opportunistic infection with fever, loose stools and abdomen tenderness. Leucopenia, thrombocytopenia, minimal pleural effusion, ascites and gall bladder wall edema prompted us to think of dengue and was found to be positive. Child improved with appropriate supportive care measures. Pediatricians should be aware of the differences in the presentation of tropical infections in children with hemato-oncological disorders. Tropical infections should be kept in mind even in children with underlying hemato-oncological conditions, to ensure diagnosis and appropriate management.

Review of the role of ultrasound in assessing plasma leakage in dengue fever and a proposed scanning protocol

AbstractBackgroundThe clinical course of dengue can range from mild to severe and predicting the course can be challenging. The World Health Organisation (WHO) recommends prognostication via the presence of warning signs, to aid in disposition and management. Plasma leakage is a key warning sign in dengue, and ultrasound can be utilised as a screening tool.ObjectivesThe objectives were to describe the literature on the use of ultrasound in dengue, summarise the findings, and propose a standardised point‐of‐care ultrasound protocol.MethodsWe reviewed the current literature on the role of ultrasound in dengue and its key features.ResultsUltrasound is a useful tool in the evaluation of patients with dengue and has been shown to be able to detect plasma leakage even prior to clinical and laboratory findings. In particular, gallbladder wall thickening is an early sign that can aid the clinician in prognosticating patients.ConclusionDetecting plasma leakage early with ultrasonography can help the clinician determine appropriate disposition and management. We propose a standardised point‐of‐care ultrasound protocol (FASD) for early detection of plasma leakage in dengue, in the routine care of dengue patients.

Angiopoietin 1 Attenuates Dysregulated Angiogenesis in the Gastrocnemius of DMD Mice.

Duchenne muscular dystrophy (DMD) is a degenerative neuromuscular disease caused by a lack of functional dystrophin. Ang 1 paracrine signalling maintains the endothelial barrier of blood vessels, preventing plasma leakage. Chronic inflammation, a consequence of DMD, causes endothelial barrier dysfunction in skeletal muscle. We aim to elucidate changes in the DMD mouse's gastrocnemius microvascular niche following local administration of Ang 1. Gastrocnemii were collected from eight-week-old mdx/utrn+/- and healthy mice. Additional DMD cohort received an intramuscular injection of Ang 1 to gastrocnemius and contralateral control. Gastrocnemii were collected for analysis after two weeks. Using immunohistochemistry and real-time quantitative reverse transcription, we demonstrated an abundance of endothelial cells in DMD mouse's gastrocnemius, but morphology and gene expression were altered. Myofiber perimeters were shorter in DMD mice. Following Ang 1 treatment, fewer endothelial cells were present, and microvessels were more circular. Vegfr1, Vegfr2, and Vegfa expression in Ang 1-treated gastronemii increased, while myofiber size distribution was consistent with vehicle-only gastrocnemii. These results suggest robust angiogenesis in DMD mice, but essential genes were underexpressed-furthermore, exogenous Ang 1 attenuated angiogenesis. Consequentially, gene expression increased. The impact must be investigated further, as Ang 1 therapy may be pivotal in restoring the skeletal muscle microvascular niche.

Gambaran Kadar Hematokrit pada Penderita Demam Berdarah Dengue di RSUD Al – Ihsan

Early signs of dengue virus infection are often nonspecific, which can result in delays in assessment. This disease can develop quickly, even in a matter of days or hours, and can result in serious conditions. The primary pathophysiology of dengue hemorrhagic fever (DHF) involves increased vascular permeability and impaired hemostasis. Increased blood vessel permeability can result in plasma leakage, hypovolemia, and even severe stress. Disturbances in hemostasis can result in thrombocytopenia and bleeding manifestations. In dengue fever sufferers, thrombocytopenia occurs due to antibodies attacking platelets, which make antigen-antibody complexes. Hematocrit levels can increase due to an increase in the number of blood cells or a decrease in the amount of plasma, which often occurs in cases of dengue fever. conversely, hematocrit levels can decrease due to an increase in plasma concentration, similar to the case of a decrease in the number of blood cells or anemia. Blood tests are very crucial in monitoring the patient's condition and determining the prognosis. Based on WHO testing guidelines, thrombocytopenia and plasma extravasation, which are reflected in blood concentrations, are crucial indicators in the assessment of dengue fever. The research method used in this research is narrative, carried out from March to May 2024 at Al-Ihsan Regional Hospital. The study population included 30 patients, and the sample was representative of the entire population. Research findings show that 24 out of 30 patients (80%) experienced an increase in hematocrit levels. Key terms: Dengue Hemorrhagic Fever, Hematocrit.

PARP15 is a Susceptibility Locus for Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome).

Vascular leakage is a deadly complication of severe infections, ranging from bacterial sepsis to malaria. Worldwide, septicemia is among the top 10 causes of lethality because of the shock and multiorgan dysfunction that arise from the host vascular response. In the monoclonal gammopathy-associated capillary leak syndrome (MG-CLS), even otherwise mundane infections induce recurrent septic-like episodes of profound microvascular hyperpermeability and shock. There are no defined genetic risk factors for MG-CLS or effective treatments for acute crises. We characterized predicted loss-of-function mutations in PARP15 (poly[ADP-ribose] polymerase 15), a protein of unknown function that is absent in mice, in patients with MG-CLS. We analyzed barrier function in PARP15-deficient vascular endothelial cells and vascular leakage in mice engineered to express WT or loss-of-function variant human PARP15. We discovered several loss-of-function PARP15 variants associated with MG-CLS. These mutations severely reduced PARP15 enzymatic function. The presence of the most frequently detected variant (G628R) correlated with clinical markers of severe vascular leakage. In human microvascular endothelial cells, PARP15 suppressed cytokine-induced barrier disruption by ADP-ribosylating the scaffold protein JIP3 (c-Jun N-terminal kinase-interacting protein 3) and inhibiting p38 MAP kinase activation. Mice expressing enzymatically inactive human PARP15(G628R) were significantly more prone to inflammation-associated vascular leakage than mice expressing WT PARP15 in a p38-dependent fashion. PARP15 represents a previously unrecognized genetic susceptibility factor for MG-CLS. PARP15-mediated ADP ribosylation is an essential and genetically determined mechanism of the human vascular response to inflammation.

ROLE OF USG IN EARLY DETECTION AND PREDICTING SEVERITY OF DENGUE INFECTION

Background: Early detection and severity assessment are crucial for managing dengue fever. Ultrasound (USG) imaging can help identify key features such as capillary leakage and organ involvement, aiding in diagnosis and prognosis. Aims: To correlate ultrasound findings with the severity of dengue infection. To evaluate USGs sensitivity in detecting early capillary leakage and its prognostic value. Methods: The study involved 66 patients (40 males, 26 females aged 12-70) with serologically confirmed dengue, observed from August 2022 to October 2023. USG was performed within 3 days of fever onset and again after 1 week. Results: Day 1-3: Gallbladder wall thickening (60.6%) and pericholecystic fluid were common. Pleural effusion (34.8%) was observed in milder cases. Day 7: Gallbladder wall thickening persisted in 89.4%. New findings included ascites (24.2%), bilateral pleural effusion (31.8%), and pericardial effusion (9.1%). Severe cases showed hepatomegaly and splenomegaly. Conclusion: USG is a valuable tool for early detection and severity assessment of dengue fever. Key findings like gallbladder wall thickening and pleural effusion can help predict disease severity and guide clinical management.

17β-Estradiol Abrogates TNF-α-Induced Human Brain Vascular Pericyte Migration by Downregulating miR-638 via ER-β.

Pericytes (PCs) contribute to brain capillary/BBB integrity and PC migration is a hallmark for brain capillary leakage following pro-inflammatory insults. Estradiol promotes endothelial barrier integrity by inhibiting tumor necrosis factor-alpha (TNF-α)-induced PC migration. However, the underlying mechanisms remain unclear. Since micro-RNAs (miRs) regulate BBB integrity and increases in miR638 and TNF-α occur in pathological events associated with capillary leakage, we hypothesize that TNF-α mediates its capillary disruptive actions via miR638 and that estradiol blocks these actions. Using quantitative reverse transcription PCR, we first assessed the modulatory effects of TNF-α on miR638. The treatment of PCs with TNF-α significantly induced miR638. Moreover, transfection with miR638 mimic induced PC migration, whereas inhibitory miR638 (anti-miR) abrogated the pro-migratory actions of TNF-α, suggesting that TNF-α stimulates PC migration via miR638. At a molecular level, the pro-migratory effects of miR638 involved the phosphorylation of ERK1/2 but not Akt. Interestingly, estradiol downregulated the constitutive and TNF-α-stimulated expression of miR638 and inhibited the TNF-α-induced migration of PCs. In PCs treated with estrogen receptor (ER) ER-α, ER-β, and GPR30 agonists, a significant downregulation in miR638 expression was solely observed in response to DPN, an ER-β agonist. DPN inhibited the pro-migratory effects of TNF-α but not miR638. Additionally, the ectopic expression of miR638 prevented the inhibitory effects of DPN on TNF-α-induced PC migration, suggesting that interference in miR638 formation plays a key role in mediating the inhibitory actions of estradiol/DPN. In conclusion, these findings provide the first evidence that estradiol inhibits TNF-α-induced PC migration by specifically downregulating miR638 via ER-β and may protect the neurovascular unit during injury/stroke via this mechanism.

Fluid Overload in Children Following Hematopoietic Cell Transplant: A Comprehensive Review.

Fluid overload significantly increases morbidity and mortality in critically ill children. Following hematopoietic cell transplant (HCT), children are at a high risk of fluid accumulation due to essential increased fluid intake for nutrition, blood products, and antimicrobials. In addition, many complications predispose these children to capillary leak and fluid overload (FO), such as sinusoidal obstruction syndrome, engraftment syndrome, sepsis, and acute kidney injury (AKI). FO > 10% occurs in nearly half of children following HCT and is associated with a lower PICU survival rate. In addition, in children with acute respiratory failure post HCT, each 1% increase in cumulative fluid balance on d 3 increases the odds of PICU mortality by 3%. Furthermore, FO worsens AKI. Tools such as the renal angina index and urinary biomarkers such as neutrophil gelatinase-associated lipocalin can help identify patients at risk of AKI and FO. Early detection, prevention, and intervention are crucial to improving outcomes in this population. Management strategies include fluid restriction, diuretics, and continuous kidney replacement therapy (CKRT) when FO exceeds 10% and other measures have failed.

Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.

Infection of lung endothelial cells with pneumococci activates the superoxide-generating enzyme NADPH oxidase 2 (NOX2), involving the pneumococcal virulence factor pneumolysin (PLY). Excessive NOX2 activity disturbs capillary barriers, but its global inhibition can impair bactericidal phagocyte activity during pneumococcal pneumonia. Depletion of the α subunit of the epithelial sodium channel (ENaC) in pulmonary endothelial cells increases expression and PMA-induced activity of NOX2. Direct ENaC activation by TIP peptide improves capillary barrier function -measured by electrical cell substrate impedance sensing in endothelial monolayers and by Evans Blue Dye incorporation in mouse lungs- following infection with pneumococci. PLY-induced hyperpermeability in HL-MVEC monolayers is abrogated by both NOX2 inhibitor gp91dstat and TIP peptide. Endothelial NOX2 expression is assessed by increased surface membrane presence of phosphorylated p47phox subunit (Western blotting) in vitro and by co-localization of CD31 and gp91phox in mouse lung slices using DuoLink, whereas NOX2-generated superoxide is measured by chemiluminescence. TIP peptide blunts PMA-induced NOX2 activity in cells expressing ENaC-α, but not in neutrophils, which lack ENaC. Conditional endothelial ENaC-α KO (enENaC-α KO) mice develop increased capillary leak upon i.t. instillation with PLY or pneumococci, compared to wild type (wt) animals. TIP peptide diminishes capillary leak in Sp-infected wt mice, without significantly increasing lung bacterial load. Lung slices from Sp-infected enENaC-α KO mice have a significantly increased endothelial NOX2 expression, as compared to infected CRE mice. In conclusion, endothelial ENaC may represent a novel therapeutic target to reduce NOX2-mediated oxidative stress and capillary leak in ARDS, without impairing host defense.

Anaplastic large cell lymphoma with concomitant Hemophagocytic Lymphohistiocytosis (HLH): hyperinflammation and capillary leakage syndrome

In our 19 years’ experience at King Chulalongkorn Memorial Hospital, we were able to observe 21 pediatric cases with anaplastic large cell lymphoma (ALCL). Of these 21 cases, 4 (19% of ALCL cases) had concurrent hemophagocytic lymphohistiocytosis (HLH). All developed fever, lymphadenopathy and exaggerated signs of capillary leakage syndrome such as generalized edema, pleural effusion or ascites. The hyperinflammation was demonstrated with fever, hypoalbuminemia and elevated inflammatory markers. A high index of suspicion is warranted to recognize concurrent HLH when patients develop cytopenia, splenomegaly, liver dysfunction and pleural or pericardial effusions. For HLH with unknown etiology but with lymphadenopathy, lymph node biopsy should be considered as a part of secondary HLH workup to rule out malignant-associated hemophagocytic syndrome. Treatment with lymphoma-directed therapy should not be contraindicated once a diagnosis of ALCL is made. Instead, one should be cautious whenever a hyperinflammatory state and multi-organ dysfunction exists because HLH-sensitive agents such as corticosteroid, etoposide, cyclosporin A, cyclophosphamide, IVIG and others should be urgently administrated. The mortality was quite high (50%) in our institution. Initial treatment with HLH protocol saved the lives of the other 2 patients (50%), both of whom were cured later with lymphoma-directed protocol.

Interferon Causes Endothelial Injury in Humans

Therapy with exogenous interferon and human conditions that feature endogenous interferon upregulation may be associated with endothelial damage that primarily involves small blood vessels. Endothelial injury associated with interferon may display different clinical expression, including thrombotic microangiopathy, Raynaud’s phenomenon, vasculopathy of dermatomyositis and atrophic papulosis, interferon-associated skin angiopathy, systemic capillary leak syndrome, collapsing glomerulopathy, interstitial lung disease, pulmonary hypertension, and retinopathy. Interferon- induced endothelial damage involves complement-mediated injury, although pathogenic mechanisms by which interferon promote abnormal complement activation on endothelial cells are not fully understood. Human interferon-γ (type II interferon) binds to heparan sulfate on the endothelial surface, suggesting that overproduction of interferon-γ may hinder factor H attachment to the same location. Absence of factor H on self surfaces promotes activation of the alternative pathway of complement and complement-mediated endothelial damage. Type I interferon typically induces the generation of antibodies. Type I interferon upregulation may elicit the formation of autoantibodies against factor H. These autoantibodies block factor H binding to endothelial surfaces, abolishing the protective effect of factor H on complement-mediated damage. In addition, interferon induces insulin resistance which is associated with reduced heparan sulfate in the extracellular matrix, including the endothelial surface. Decreased amount of heparan sulfate suppresses factor H attachment, promoting activation of the alternative pathway of complement. Complement blockade with eculizumab (a monoclonal antibody against C5) improves endothelial damage in patients with thrombotic microangiopathy and other situations associated with interferon upregulation and interferon-induced endothelial injury, suggesting that complement-mediated injury is clinically relevant under conditions that feature interferon overproduction.

The Angiopoietin-Tie-2 Axis in Children and Young Adults with Dengue Virus Infection in the Philippines.

Dengue virus (DENV) infection is associated with plasma leakage, which may progress to shock. The angiopoietin (Ang)-tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (Tie-2) axis regulates endothelial permeability. We examined the clinical utility of Ang-1, Ang-2, and the Ang-2-to-Ang-1 ratio for prediction of progression to severe DENV in a prospective cohort study of children and young adults (age 1 to <26 years) with DENV infection. Ang-1, Ang-2, Tie-2 were measured at presentation to an outpatient clinic in the Philippines from stored plasma by multiplex Luminex® assay. Patients were followed prospectively to document the clinical course (hospitalization, length of stay, intravenous fluid resuscitation, and transfer to a higher level facility). We included 244 patients (median age 9 years, 40% female). At presentation, 63 patients (26%) had uncomplicated dengue, 179 (73%) had dengue with warning signs, and 2 (0.82%) had severe dengue. One hundred eighty-one patients (74%) were hospitalized. Ang-1 levels were lower and Ang-2 higher in patients who required hospitalization. Ang-2-to-Ang-1 ratio >1 was associated with a relative risk of hospitalization of 1.20 (95% CI: 1.03-1.36, P = 0.016). A higher Ang-2-to-Ang-1 ratio was associated with longer length of hospital stay, higher frequency of transfer to a higher level facility, larger intravenous fluid requirement, hemoconcentration, and thrombocytopenia. Angiopoietin-2 was correlated with procalcitonin (Kendall's τ = 0.17, P = 0.00012), a marker of systemic inflammation, as well as soluble vascular cell adhesion molecule-1 (τ = 0.22, P <0.0001) and Endoglin (τ = 0.14, P = 0.0017), markers of endothelial activation. In conclusion, altered Ang-2-to-Ang-1 ratio can be detected early in the course of DENV infection and predicts clinically meaningful events (hospitalization, length of stay, and fluid resuscitation).

Caprock Safety Evaluation Method in CCUS Based on Latin Hypercube Sampling: A case study of a block reservoir

Abstract CO2 geological sequestration is one of the essential means to achieve carbon neutrality goals. However, substantial CO2 sequestration in formations can lead to leakage issues, primarily through the caprock, involving caprock rupture, leakage along caprock fractures/faults, and capillary leakage. Therefore, establishing a method to assess the safety of the caprock during CO2 storage processes is crucial. Firstly, a numerical simulation model is constructed based on parameters from the target block to study the influences of reservoir property, development parameters, and caprock parameters on CO2 flooding, gas injection, and CO2 storage. Latin hypercube sampling is employed for scheme design and subsequent result analysis, applying Spearman’s method to analyze the controlling factors in each CO2 storage. Secondly, using continuous gas flooding as an example, the migration pattern of CO2 in the formation is investigated, and the influence of the formation pressure distribution on caprock safety is analyzed. Finally, considering the comprehensive impact of different parameters on caprock safety, a fuzzy comprehensive evaluation of caprock safety in the target block is conducted. The study indicates that caprock permeability is the most critical factor affecting safety operation across all storage stages, with respective highest positive correlation coefficients of 0.413, 0.356, and 0.221 in different stages. The migration of CO2 in the formation is primarily influenced by the distribution of injection wells and gas migration channels. The established quantitative evaluation standard for caprock safety in the target block calculates a suitability degree of 3.43, suggesting a relatively secure caprock in the block suitable for achieving long-term stable CO2 storage. This research provides theoretical support for the safety analysis of caprock in different stages of CO2 flooding and storage, offering a scientific basis for the safety operation of CCUS schemes.

Neonatal ascites, leading to the diagnosis of congenital dengue with plasma leakage.

Although Cambodia is a dengue-endemic country, mother-to-child transmission of dengue virus has yet to be documented. We report a rare case for congenital dengue diagnosed by RT-PCR in a 4-day-old neonate with ascites. The neonate was initially treated for suspected perinatal infection. The management was supportive.

Early intervention of 5% albumin shown superior control of vascular integrity and function compared to ringer’s lactatein hospitalized adult with grade I & II Dengue hemorrhagic fever: a multicenter randomized controlled trial in Indonesia

BackgroundDengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients.MethodsWe conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer’s Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively.ResultsAdult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group.ConclusionEarly intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay.Trial registrationThe study was registered to www.clinicaltrial.gov with trial registration number NCT04076254, and registration date October 31st 2016.

Utilizing the '5 in 1 Magic Touch' CCRTV method for early detection of severe dengue warning signs in pediatric patients: A case study from a Type C Hospital in Indonesia

Background: Dengue fever, prevalent in tropical and subtropical regions, is recognized by WHO as a significant global health threat. Early detection of severe dengue symptoms, especially in resource-limited settings, is critical for patient outcomes. The "5 in 1 Magic Touch - CCRTV" method, which evaluates Color, Capillary Refill Time, Temperature, Pulse Rate, and Pulse Volume, provides a simple yet effective approach to monitor hemodynamics and identify early warning signs of severe dengue. Case Description: In a case study, a 3-year-old boy was admitted with fever, shortness of breath, weakness, nausea, vomiting, and epigastric pain. On the third day, he entered a critical phase with symptoms of pale extremities, delayed capillary refill time, high fever, and a weak, rapid pulse. Thorax examination revealed severe plasma leakage, pulmonary edema, and right pleural effusion, indicating a pre-shock state. The patient required close clinical monitoring, regular fluid balance management, and frequent blood tests to guide treatment. Conclusion:The CCRTV assessment method allowed for the early identification of the pre-shock condition, facilitating timely and appropriate intervention. This case highlights the potential of the CCRTV method for improving prognosis in severe dengue cases. The effectiveness of this method warrants further research, particularly in its ability to predict outcomes and improve recovery rates in children with severe dengue.

Polypropylene membrane with gradient-distributed covalent organic framework for highly efficient blood oxygenation

Hollow fiber membrane (HFM) is widely used for extracorporeal membrane oxygenator (ECMO) because of large membrane area, high packing density, self-supporting structure and good flexibility. However, polymeric HFMs often suffer from a trade-off between gas permeability and anti-plasma leakage performance. In this study, HFMs with gradient structure were prepared by introducing COF-42 as fillers into the polypropylene (PP) matrix through surface segregation. The enriched COF-42 near the upper surface endowed the membrane a gradient structure to reduce the plasma leakage and improve gas permeability. Compared with PP membranes, PP/COF-42 oxygenation membranes retained good blood compatibility and higher mechanical properties. The PP/COF-42–0.5 HFMs exhibited O2 exchange rate of ∼ 342.6 ml min−1 m−2 and CO2 exchange rate of ∼ 989.6 ml min−1 m−2, which was about 218.7 % and 15.4 % larger than that of the PP HFMs, respectively. Moreover, the simulated plasma leakage time could reach 124 h, which was about 21 times longer than that of PP HFMs. The membranes exhibited excellent blood oxygenation performance and anti-plasma leakage performance, which had great potential in ECMO.

Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion.

Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.