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OBJECTIVES: Host factors that regulate plasma leakage during severe dengue (SD) are under investigation. While PECAM-1 and MMP-14 have been reported to regulate vascular integrity, their role in dengue pathogenesis remains unexplored. This study aims to assess the association of soluble PECAM-1 and MMP-14 with dengue severity symptoms. PATIENTS AND METHODS: Serum levels of PECAM-1 and MMP-14 were evaluated in dengue (N-25) comprising 10 severe dengue (SD) and 15 non-severe dengue, 10 other febrile illnesses along with healthy controls (N-10) using ELISA. Protein levels were assessed using in vitro models. RESULTS: From febrile to critical phase, a significant increase in PECAM-1 (P≤0.01) & MMP-14 (P≤0.001) levels were observed in SD cases compared to non-severe or other controls. Serum levels of PECAM-1 and MMP 14 were found to be positively (P≤0.001) associated. Soluble PECAM-1 levels of severe defervescence showed a positive correlation (P≤0.001) with plasma leakage and an inverse relationship (P≤0.001) with platelet count. In vitro analysis revealed elevated expression of study proteins in endothelial cells activated with severe serum samples. To the best of our knowledge, this is the first report to explore PECAM-1 or MMP-14 dynamics and their association with dengue severity. CONCLUSION: Higher shedding of sPECAM-1 accompanied with increased levels of MMP-14 is strongly associated with severe dengue. However, the exact role of serum PECAM-1 in disease prognosis requires further studies.

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Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. STATEMENT OF SIGNIFICANCE: A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.

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Materiales Biocompatibles Revestidos , Oxigenación por Membrana Extracorpórea , Animales , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Heparina/química , Heparina/farmacología , Humanos , Polipropilenos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Fibrinolíticos/farmacología , Fibrinolíticos/química , Membranas Artificiales , Adsorción , Trombosis/prevención & control , Fosforilcolina/química , Fosforilcolina/análogos & derivados , Polímeros/química

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Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage. Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Results: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. Conclusions: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Funding: Wellcome Trust and European Union Seventh Framework Programme.

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Dengue , Viremia , Humanos , Vietnam/epidemiología , Viremia/sangre , Recuento de Plaquetas , Dengue/sangre , Dengue/epidemiología , Masculino , Femenino , Adulto , Cinética , Persona de Mediana Edad , Virus del Dengue , Adulto Joven , Adolescente

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BACKGROUND: Early identification of plasma leakage may guide treatment decisions in dengue patients. This study evaluated the value of point-of-care ultrasound (POCUS) to detect plasma leakage and predict hospitalization or referral to a higher level of care in suspected dengue patients under routine conditions at a primary care facility in Colombia. METHODS: We conducted a cohort study between April 2019 and March 2020 in a primary care hospital in Cali, Colombia. We prospectively included and followed 178 patients who were at least 2 years old with fever of less than 10 days and clinician-suspected dengue. A trained general practitioner performed a standardized POCUS protocol. Images were quality-rated and overread by an expert radiologist, and her results and those of the general practitioner were compared using the Kappa index. Logistic regression was used to identify factors associated with plasma leakage at enrollment and explore its prognostic value regarding hospital admission or referral to a higher level of care. RESULTS: Half (49.6%) POCUS images were of suitable quality to be interpreted. The proportion of plasma leakage reported by the radiologist was 85.1% (95% CI: 78.6-90.2%) and 47.2% by the study physician (Kappa = 0.25, 95% CI: 0.15-0.35). The most frequent ultrasound findings were ascites (hepatorenal 87.2%, splenorenal 64%, or pelvic 21.8%) and gallbladder wall thickening (10.5%). Plasma leakage was higher in subjects with thrombocytopenia (aOR = 4, 95% CI: 1.3-12.1) and lower in patients 30-59 years old (aOR = 0.1, 95% CI: 0.0-0.4) than in those 18 years old or younger. POCUS evidence of plasma leakage (aOR = 8.2, 95% CI: 2.2-29.9), thrombocytopenia (aOR = 6.3, 95% CI: 2.4-16.0) and pulse pressure (aOR = 1.1, 95% CI: 1.07-1.2) were associated with hospital admission or referral to a higher level of care. CONCLUSIONS: Ultrasound is useful to detect plasma leakage in primary care and, challenges remain to guarantee high-quality images and diagnostic accuracy, for which a standardized dengue POCUS protocol and training program is needed.

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Dengue , Sistemas de Atención de Punto , Humanos , Femenino , Preescolar , Adulto , Persona de Mediana Edad , Adolescente , Colombia , Estudios de Cohortes , Radiólogos , Atención Primaria de Salud , Dengue/diagnóstico por imagen

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BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

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Dengue , Derrame Pleural , Dengue Grave , Adulto , Niño , Humanos , Dengue Grave/complicaciones , Dengue Grave/diagnóstico por imagen , Dengue Grave/epidemiología , Exudados y Transudados , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/epidemiología , Derrame Pleural/complicaciones , Plasma , Ultrasonografía , Dengue/complicaciones , Dengue/diagnóstico por imagen , Dengue/epidemiología

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@#The prevalence of dengue infection poses a great public health concern among people living in tropical and subtropical countries like the Philippines. Just recently in 2019, the Philippines had a dengue virus (DENV) outbreak where nearly half of the mortalities were children between 5 and 9 years of age, and around 73% of confirmed DENV cases were under the age of 19. Children are disproportionately affected and are considered to be highly vulnerable to severe dengue infection compared to adults due to several factors. These include: immunological differences--poorly developed immune systems, making them more susceptible to the virus; smaller body sizes and weight means that they are more likely to experience severe symptoms; and their tendency to play outdoors, make them more exposed to mosquito bites. Hence, this article provides an overview of the current understanding for the vulnerability of children to severe dengue infection compared to adults

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Virus del Dengue , Dengue Grave

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Extracorporeal membrane oxygenation is a technique that provides short-term supports to the heart and lungs. It removes CO2 from the blood and provides enough oxygen, which is a huge help in the fight against COVID-19. As the key component, the artificial lung membranes have evolved in three generations including silicon, polypropylene and poly (4-methyl-1-pentene). Herein, we for the first time design and fabricate a novel poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite (TFC) membrane with the anticoagulant coating composed of poly (sodium 4-styrenesulfonate) and cross-linked poly (vinyl alcohol). Poly (sodium 4-styrenesulfonate) provides sulfonic acid groups to inhibit the coagulant factors (FVIII and FXII), and cross-linked poly (vinyl alcohol) increase the stability of the anticoagulant coating and further improve the hydrophilicity via abundant hydroxyl groups to depress the protein adsorption. Long-term anticoagulant property was demonstrated by whole human blood for 28 days. Blood compatibility was evaluated by hemolysis rate, anticoagulation activity (APTT, TT and PT), complement activation, platelet activation and contact activation. Pure CO2, O2 and N2 permeation rates were determined to evaluate the mass transfer properties of PMP/PP TFC membranes. Gas permeation results revealed that gas permeation flux increased in the TFC membranes because of the decrease of crystallinity. Overall, the so prepared PMP/PP membrane shows good CO2/O2 selectivity and blood compatibility as novel TFC artificial lung membrane.

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BACKGROUND: Plasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage. METHODS: The dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay. RESULTS: MMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients. CONCLUSION: MMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.

Asunto(s)

Virus del Dengue , Dengue , Factores Inhibidores de la Migración de Macrófagos , Dengue Grave , Humanos , Dengue Grave/complicaciones , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Metaloproteinasa 3 de la Matriz , Pronóstico , Biomarcadores , Dengue/diagnóstico , Dengue/etiología

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Dengue is an important arboviral disease in the tropics and subtropics. Although mild to moderate elevation of liver transaminases is a common phenomenon, dengue infection leading to hepatic failure is a rare complication in adults. We present a case of dengue fever in a young adult, leading to the rare complication of acute liver failure, without dengue shock syndrome. We tried evidence-based management with therapeutic plasma exchange, which led to a significant improvement in liver function.

RESUMEN

BACKGROUND: We evaluated clinical and laboratory findings among patients with nonsevere or severe dengue in Puerto Rico to examine whether clinical manifestations vary by age. METHODS: During 2012-2014, we enrolled patients who arrived at the emergency department with fever or history of fever within 7 days of presentation. Serum samples were tested for dengue virus (DENV) by reverse transcriptase-polymerase chain reaction (RT-PCR) and IgM enzyme-linked immunosorbent assay (ELISA). Severe dengue was defined as severe plasma leakage or shock, severe bleeding, or organ involvement at presentation, during hospitalization, or follow-up. RESULTS: Of 1089 dengue patients identified, 281 (26%) were severe. Compared to those with nonsevere dengue, patients with severe dengue were more often aged 10-19 years (55% vs 40%, P < .001) and hospitalized (87% vs 30%, P < .001). Severe plasma leakage or shock was more common among children aged 0-9 (59%) or 10-19 years (86%) than adults (49%) (P < .01). Severe bleeding was less common among 10-19 year olds (24%) compared to 0-9 year olds (45%) and adults (52%; P < .01). CONCLUSIONS: Severe plasma leakage was the most common presentation among children, highlighting important differences from adults. Vaccination against dengue could help prevent severe dengue among children in Puerto Rico.

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Virus del Dengue , Dengue , Dengue Grave , Adulto , Niño , Humanos , Virus del Dengue/genética , Dengue/epidemiología , Dengue Grave/epidemiología , Puerto Rico/epidemiología , Fiebre

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According to the WHO 2009 classification, dengue with warning signs is at the risk of developing severe form of dengue disease. One of the most important warning signs is plasma leakage, which can be a serious complication associated with higher morbidity and mortality. We report that the frequency of CD4+CD8+ double-positive (DP) T cells is significantly increased in patients at risk of developing plasma leakage. Transcriptomic analysis demonstrated that CD4+CD8+ DP cells were distinct from CD4+ Single Positive (SP) T cells but co-clustered with CD8+ SP cells, indicating a largely similar transcriptional profile. Twenty significant differentially expressed (DE) genes were identified between CD4+CD8+ DP and CD8+ SP cells. These genes encode OX40 and CCR4 proteins as well as other molecules associated with cell signaling on the cell surface (NT5E, MXRA8, and PTPRK). While comparing the profile of gene expression in CD4+CD8+ DP cells from patients with and without warning signs of plasma leakage, similar expression profile was observed, implying a role of CD4+CD8+ DP cells in plasma leakage through a quantitative increase rather than functional alteration. This study provided novel insight into the host immune response during the acute febrile phase of DENV infection and the role of CD4+CD8+ DP T cells in the pathogenesis of plasma leakage.

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Dengue/sangre , Dengue/inmunología , Subgrupos de Linfocitos T/metabolismo , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Femenino , Humanos , Recuento de Linfocitos , Masculino , Plasma , Dengue Grave/sangre , Dengue Grave/inmunología , Subgrupos de Linfocitos T/inmunología , Transcriptoma , Adulto Joven

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Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay. Seventeen of 115 patients (14.8%) experienced bleeding manifestations. High soluble delta-like ligand 1 (sDLL1) plasma levels was associated with bleeding (median, 15 674 vs 7117 pg/mL; P < .001). Receiver operating characteristic (ROC) curve analysis demonstrated that sDLL1 had the best test performance (area under the ROC curve, 0.852), with 88% sensitivity and 84% specificity. The combination with alanine aminotransferase and aspartate aminotransferase slightly increased sDLL1 performance. sDLL1 may be useful to guide clinical management of patients with patients in endemic settings.

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Dengue , Dengue Grave , Alanina Transaminasa , Aspartato Aminotransferasas , Proteínas de Unión al Calcio , Dengue/complicaciones , Humanos , Ligandos , Proteínas de la Membrana , Dengue Grave/complicaciones

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Plasma leakage is a precursor to life-threatening complications of dengue, but this group is poorly defined and not often reported in literature. Patients with Dengue haemorrhagic fever (DHF) as defined in the 1997 World Health Organization classification are often reported, and they all have plasma leakage, but some patients with plasma leakage do not meet the definition of DHF. The study aims to estimate the frequency of plasma leakage and DHF (as a surrogate of plasma leakage) in dengue and its variations based on virus serotype, geography, patient gender and pre-existing immunity to dengue. PUBMED, Scopus, EMBASE, CINAHL and Web of Science were searched for prospective observational studies reporting on plasma leakage or DHF. Quality of data was assessed using the NIH quality assessment tool for cohort studies. Forty-three studies that recruited 15,794 confirmed dengue patients were eligible. Cumulative frequency of plasma leakage was 36.8% (15 studies, 1642/4462, 95% CI 35.4-38.2%), but surprisingly the estimated cumulative frequency of DHF was higher (45.7%, 32 studies, 4758/10417, 95% CI 44.7-46.6%), indicating that current medical literature over-reports DHF or under-reports plasma leakage. Therefore, a reliable estimate for the proportion of dengue patients developing plasma leakage cannot be derived from existing medical literature even after applying rigorous inclusion criteria to select homogenous studies. Plasma leakage is an important marker of "at-risk" dengue patients and standardizing its definition, diagnosis and reporting should be a priority in research and global policy.

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Dengue Grave , Humanos , Serogrupo , Dengue Grave/epidemiología , Organización Mundial de la Salud , Estudios Observacionales como Asunto

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The objective of this study is to clarify the pore structure of ECMO membranes by using our approach and theoretically validate the risk of SARS-CoV-2 permeation. There has not been any direct evidence for SARS-CoV-2 leakage through the membrane in ECMO support for critically ill COVID-19 patients. The precise pore structure of recent membranes was elucidated by direct microscopic observation for the first time. The three types of membranes, polypropylene, polypropylene coated with thin silicone layer, and polymethylpentene (PMP), have unique pore structures, and the pore structures on the inner and outer surfaces of the membranes are completely different anisotropic structures. From these data, the partition coefficients and intramembrane diffusion coefficients of SARS-CoV-2 were quantified using the membrane transport model. Therefore, SARS-CoV-2 may permeate the membrane wall with the plasma filtration flow or wet lung. The risk of SARS-CoV-2 permeation is completely different due to each anisotropic pore structure. We theoretically demonstrate that SARS-CoV-2 is highly likely to permeate the membrane transporting from the patient's blood to the gas side, and may diffuse from the gas side outlet port of ECMO leading to the extra-circulatory spread of the SARS-CoV-2 (ECMO infection). Development of a new generation of nanoscale membrane confirmation is proposed for next-generation extracorporeal membrane oxygenator and system with long-term durability is envisaged.

RESUMEN

Neutrophil extracellular traps (NETs) are increasingly recognized to play a role in the pathogenesis of viral infections, including dengue. NETs can be formed NADPH oxidase (NOX)-dependently or NOX-independently. NOX-independent NETs can be induced by activated platelets and are very potent in activating the endothelium. Platelet activation with thrombocytopenia and endothelial dysfunction are prominent features of dengue virus infection. We postulated that dengue infection is associated with NOX-independent NET formation, which is related to platelet activation, endothelial perturbation and increased vascular permeability. Using our specific NET assays, we investigated the time course of NET formation in a cohort of Indonesian dengue patients. We found that plasma levels of NETs were profoundly elevated and that these NETs were predominantly NOX-independent NETs. During early recovery phase (7-13 days from fever onset), total NETs correlated negatively with platelet number and positively with platelet P-selectin expression, the binding of von Willebrand factor to platelets and levels of Syndecan-1. Patients with gall bladder wall thickening, an early marker of plasma leakage, had a higher median level of total NETs. Ex vivo, platelets induced NOX-independent NET formation in a dengue virus non-structural protein 1 (NS1)-dependent manner. We conclude that NOX-independent NET formation is enhanced in dengue, which is most likely mediated by NS1 and activated platelets.

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Plaquetas/metabolismo , Virus del Dengue/patogenicidad , Dengue/enzimología , Trampas Extracelulares/metabolismo , NADPH Oxidasas/metabolismo , Neutrófilos/enzimología , Activación Plaquetaria , Adolescente , Adulto , Plaquetas/inmunología , Plaquetas/virología , Estudios de Casos y Controles , Células Cultivadas , Dengue/sangre , Dengue/inmunología , Dengue/virología , Virus del Dengue/inmunología , Virus del Dengue/metabolismo , Trampas Extracelulares/virología , Femenino , Interacciones Huésped-Patógeno , Humanos , Indonesia , Masculino , Neutrófilos/inmunología , Neutrófilos/virología , Estudios Prospectivos , Proteínas no Estructurales Virales/metabolismo , Adulto Joven

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PURPOSE: Purpose: Condensation that clogs the hollow fibers of the oxygenation and accumulation of plasma leaks reduces oxygenated lung capacity. In this study, artificial We evaluated whether monitoring changes in lung gas inlet pressure was a way to predict these complications. METHODS: Changes in gas inlet pressure and oxygenation capacity of three different prostheses (BIOCUBE6000, EXCELUNG PRIME, and Capiox-LX) Evaluated the relationship. When simulating plasma leakage using BIOCUBE6000, sodium dodecyl sulfate (SDS) (1%, 0.1%, A solution of 0.01%, and RO water) reduced surface tension. During 120 minutes of circulation, changes in gas inlet pressure and leakage from the membrane into the gas flow path The amount of fluid was measured. RESULTS: There was a significant negative correlation between the gas inlet pressure changes and the oxygenation capacity of all three oxygenators (BIOCUBE6000: R2 = 0.957, EXCELUNG PRIME: R2 = 0.946, Capiox-LX: R2 = 0.878). After 120 min of SDS solution circulation using the BIOCUBE6000, both the gas inlet pressure and the volume of fluid leaking from the membrane into the gas flow path increased in proportion to the SDS solution concentration: RO water (0.56 ± 0.11 mmHg and 16.67 mL ± 0.94 mL), 0.01% SDS (0.98 ± 0.11 mmHg and 23.3 ± 0.47 mL,) 0.1% SDS (1.64 ± 0.21 mmHg and 29.0 ± 1.63 mL), and 1%SDS (14.3 ± 0.27 mmHg and 36.7 ± 0.47 mL) (n = 3). CONCLUSION: This study confirmed that monitoring the gas inlet pressure changes of an oxygenator during ECMO is clinically useful.

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Oxigenación por Membrana Extracorpórea/métodos , Oxígeno/sangre , Oxigenadores de Membrana , Humanos

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OBJECTIVES: To compare the traditional haematocrit-based criteria (>20% rise above baseline) with ultrasonography for diagnosing plasma leakage in dengue fever and to identify clinical indicators for triaging patients in resource-limited settings when the demand for ultrasonography is high. METHODS: The Colombo Dengue Study is a prospective observational cohort study recruiting dengue patients in the first three days of dengue fever, before plasma leakage. Serial haematocrit assessments and ultrasonography were performed in patients recruited from October 2017 to February 2020. Clinical signs/symptoms and laboratory investigation results independently associated with ultrasound detected plasma leakage were identified with a derivation cohort and confirmed in a validation cohort. RESULTS: 129 of 426 patients had ultrasonography-confirmed plasma leakage while 146 had a haematocrit rise >20%. Those positive on ultrasonography were also likely to fulfil the haematocrit-based criteria (OR: 4.42, 95% CI: 2.85-6.86), but the two groups did not overlap fully. In the derivation cohort (n = 317), platelet count <97 000/µl, AST/ALT > 51 IU/l and having abdominal pain in the first three days of fever were independent predictors of ultrasound-detected plasma leakage. In the validation cohort (n = 109), the combination of low platelet count and high aminotransferase level had better predictive capacity in terms of sensitivity and specificity. CONCLUSION: Dengue patients should be monitored with both serial haematocrit and ultrasonography whenever possible and plasma leakage should be diagnosed by either one of these criteria. If accessibility to scans is limited, platelet count, serum transaminase levels and presence of abdominal pain are useful to triage patients.

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Dengue Grave/diagnóstico , Triaje , Ascitis/diagnóstico por imagen , Estudios de Cohortes , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Dengue Grave/diagnóstico por imagen , Sri Lanka , Ultrasonografía

RESUMEN

BACKGROUND: One of the generally accepted constructs of dengue pathogenesis is that clinical disease severity is at least partially dependent upon plasma viremia, yet data on plasma viremia in primary versus secondary infections and in relation to clinically relevant endpoints remain limited and contradictory. METHODS: Using a large database comprising detailed clinical and laboratory characterization of Vietnamese participants enrolled in a series of research studies executed over a 15-year period, we explored relationships between plasma viremia measured by reverse transcription-polymerase chain reaction and 3 clinically relevant endpoints-severe dengue, plasma leakage, and hospitalization-in the dengue-confirmed cases. All 4 dengue serotypes and both primary and secondary infections were well represented. In our logistic regression models we allowed for a nonlinear effect of viremia and for associations between viremia and outcome to differ by age, serotype, host immune status, and illness day at study enrollment. RESULTS: Among 5642 dengue-confirmed cases we identified 259 (4.6%) severe dengue cases, 701 (12.4%) patients with plasma leakage, and 1441 of 4008 (40.0%) patients recruited in outpatient settings who were subsequently hospitalized. From the early febrile phase onwards, higher viremia increased the risk of developing all 3 endpoints, but effect sizes were modest (ORs ranging from 1.12-1.27 per 1-log increase) compared with the effects of a secondary immune response (ORs, 1.67-7.76). The associations were consistent across age, serotype, and immune status groups, and in the various sensitivity and subgroup analyses we undertook. CONCLUSIONS: Higher plasma viremia is associated with increased dengue severity, regardless of serotype or immune status.

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Virus del Dengue , Dengue , Pueblo Asiatico , Dengue/epidemiología , Humanos , Serogrupo , Viremia

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Dengue infection may manifest as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). The World Health Organization (WHO) came up with the term "expanded dengue syndrome" (EDS) to designate cases which do not fall into either DHF or DSS, with unusual manifestations in other organs such as the cardiovascular system, the nervous system, the kidneys, the gut, and the hematological system, which have been increasingly reported and called EDS. Furthermore, EDS is becoming widespread globally with unusual features and increased severity. There are increasing reports of under-recognized and infrequent manifestations with severe organ involvement. This review gives knowledge of expanded dengue syndrome which helps to catch the diagnosis of dengue early, particularly during the ongoing epidemics and escaping from further series of unnecessary investigations.

RESUMEN

About 2.5 billion people are living at a higher risk of dengue fever in hundreds of tropical and sub-tropical countries. Treatment of dengue fever is quite complicated and challenging because of the lack of effective treatment approaches. We herein report a rare case of a 25-year-old female with a past medical history of haemophilia A, suffering from dengue fever, pleural effusion, earache, myalgia, headache, and vomiting. Dengue was confirmed by the non-structural protein 1 (NS1) antigen and immunoglobulin M (IgM) antibody test. She had low blood pressure (80/60 mmHg), frequent vomiting, and low platelet count during hospitalization. Moreover, a genetic disorder like haemophilia with plasma leakage and earache made the patient's condition worse. However, by repeated platelet infusion, the platelet counts elevated and the patient was discharged from the hospital after nine days. Complete recovery was achieved after 27 days. This is a rare case of dengue; physicians should be aware of the severity of the disease and its management tactics. More discussion and research need to be carried out to develop an effective and optimized treatment and management options to reduce the mortality and morbidity due to dengue fever with a co-morbid disease.