6,201 research outputs found

    Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

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    BackgroundGlycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.MethodsNuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48).ResultsGlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset.ConclusionsHigh levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients

    Compassionate use of convalescent plasma for the management of severe pneumonia in critically ill COVID-19 patients-a single center experience, Kerala, India

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    We assessed treatment effectiveness with convalescent plasma in critically ill COVID-19 pneumonia patients and their association with reduction in C reactive protein level as a sensitive inflammatory marker to the ongoing cytokine storm. Retrospective cohort study based on the detailed electronic medical chart review. The primary outcome was a clinical improvement on day 14, defined as the reduction in cytokine storm as demonstrated by a drop in acute phase reactant C reactive protein; de-escalation from the prior mode of oxygen delivery or not on mechanical ventilation in critically ill COVID-19 patients. C reactive protein was measured by using immunoturbidimetry. IgG antibody against spike protein S1 was measured by chemiluminescent immunoassay. Of 14 patients, all had severe COVID-19 pneumonia [category C], and 9 (64%) were mechanically ventilated soon after the admission into the medical intensive care unit. De-escalation of the oxygenation strategy mode was noted in 11 (79%) patients after convalescent plasma infusion. All patients showed a significant drop in C reactive protein when compared to pre-infusion and post-infusion day 5.  Early compassionate use of convalescent plasma with higher titters of IgG antibodies against S1may positively benefit the overall outcome in critically ill COVID-19 patients with severe pneumonia

    Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

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    The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

    Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response

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    BACKGROUNDNeutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated. METHODSWe conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7-11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends. RESULTSIn this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1-8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1-11; P = 0.034). CONCLUSIONOur data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies. TRIAL REGISTRATIONClinicalTrials.gov NCT04869072. FUNDINGThis study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program "Comprehensive Genomic Pathogen Detection" of the University of Zurich

    Prothrombin Fragment 1.2 (F1.2) in Relation with Plasma Leakage Dan Thrombocytopenia in Dengue Infection

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    Latar belakang: Manifestasi klinis demam berdarah Dengue (DBD) adalah kebocoran plasma dan trombositopenia. Salah satu teori penyebab kedua hal tersebut adalah kadar trombin yang meningkat akibat aktivasi koagulasi. Kadar trombin dapat diwakili oleh kadar F1.2. Tujuan penelitian ini adalah untuk mengetahui hubungan antara kadar F1.2 dengan kebocoran plasma dan trombositopenia pada infeksi Dengue. Metode: Desain penelitian ini adalah potong lintang, mengggunakan plasma EDTA dari pasien terinfeksi virus Dengue. Subyek penelitian adalah 10 subyek dengan kebocoran plasma dan 10 subyek tanpa kebocoran plasma pada infeksi Dengue, 6 sampel berpasangan untuk perbandingan fase kritis dan fase konvalesen, 26 sampel untuk uji korelasi antara kadar F1.2 dengan jumlah trombosit. Hasil: Penelitian menunjukkan kadar F1.2 pada pasien terinfeksi virus Dengue dengan kebocoran plasma (rerata ± 2SD) 147,4 ± 105,82 pg/mL lebih tinggi secara bermakna dibanding tanpa kebocoran plasma 51,3 ±39,92 pg/mL. Kadar F1.2 pada fase kritis dengan median 186,3 (108,6-223,2) pg/mL lebih tinggi secara bermakna dibanding fase konvalesen 46,5 (27,4-51,9) pg/mL. Terdapat korelasi negatif yang bermakna dengan kekuatan sedang antara kadar F1.2 dengan jumlah trombosit, nilai r = - 0,609. Kesimpulan: Terdapat peningkatan aktivasi koagulasi yang ditunjukkan dengan peningkatan kadar F1.2 pada fase kritis, berkaitan dengan kebocoran plasma dan trombositopenia pada pasien terinfeksi virus Dengue. Kata kunci: infeksi Dengue, kebocoran plasma, trombin, fragmen protrombin (F1.2), trombositopenia Background: Clinical manifestations of Dengue hemorrhagic fever are plasma leakage and thrombocytopenia. Both manifestations are thought to be caused by an increased thrombin level due to activation of coagulation. The aim of this study is to look for any association between F1.2 level and plasma leakage and also between F1.2 level and thrombocytopenia in Dengue infected patients. Methods: This study used EDTA plasma from patients infected with Dengue virus. The study design was cross sectional. The thrombin level was represented by the prothrombin fragment 1.2 (F1.2) level. Twenty subjects were enrolled in this study, consisted of 10 subjects with plasma leakage and 10 without plasma leakage, 6 pairs of samples in critical phase and convalescent phase, 26 samples for correlation test between F1.2 level and platelet count. Results: In this study, it was found that the F1.2 level in patients with plasma leakage (mean ± 2 SD) 147.4 ± 105.82 pg/mL is significantly higher compared to patients without plasma leakage 51.3 ±39.92 pg/mL, and the F1.2 level in critical phase has a median of 186.3 (108.6-223.2) pg/mL which is significantly higher compared to convalescent phase 46.5(27.4-51.9) pg/mL. Also it was found that a medium negative correlation between F1.2 level and the thrombocyte count existed, r = - 0.609. Conclusion: The results of the study suggest that there was increased coagulation activation at critical phase in patients infected with Dengue virus associated with plasma leakage and thrombocytopenia
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